Pharmacogenomics, pharmacokinetics and pharmacodynamics: interaction with biological differences between men and women

Pharmacological response depends on multiple factors and one of them is sex–gender. Data on the specific effects of sex–gender on pharmacokinetics, as well as the safety and efficacy of numerous medications, are beginning to emerge. Nevertheless, the recruitment of women for clinical research is inadequate, especially during the first phases. In general, pharmacokinetic differences between males and females are more numerous and consistent than disparities in pharmacodynamics. However, sex–gender pharmacodynamic differences are now increasingly being identified at the molecular level. It is now even becoming apparent that sex–gender influences pharmacogenomics and pharmacogenetics. Sex‐related differences have been reported for several parameters, and it is consistently shown that women have a worse safety profile, with drug adverse reactions being more frequent and severe in women than in men. Overall, the pharmacological status of women is less well studied than that of men and deserves much more attention. The design of clinical and preclinical studies should have a sex–gender‐based approach with the aim of tailoring therapies to an individual's needs and concerns.

[1]  R. Greenblatt,et al.  Sex differences in pharmacokinetics and pharmacodynamics. , 2004, Annual review of pharmacology and toxicology.

[2]  C. Melloni,et al.  Representation of Women in Randomized Clinical Trials of Cardiovascular Disease Prevention , 2010, Current Cardiovascular Risk Reports.

[3]  Adam J Pawson,et al.  The Concise Guide to Pharmacology 2013/14: Overview , 2013, British journal of pharmacology.

[4]  P. Landi,et al.  Metabolic syndrome and major depression , 2013, CNS Spectrums.

[5]  J. Dallongeville,et al.  Discontinuation of statin therapy due to muscular side effects: a survey in real life. , 2013, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[6]  G. Mercuro,et al.  Regular cigarette smoking influences the transsulfuration pathway, endothelial function, and inflammation biomarkers in a sex-gender specific manner in healthy young humans. , 2013, American journal of translational research.

[7]  S. de Servi,et al.  Meta-analysis of impact of different types and doses of statins on new-onset diabetes mellitus. , 2013, The American journal of cardiology.

[8]  M. Schwab,et al.  Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. , 2013, Pharmacology & therapeutics.

[9]  D. Marazziti,et al.  Pharmacokinetics and pharmacodinamics of psychotropic drugs: effect of sex , 2013, CNS Spectrums.

[10]  J. Rossouw,et al.  Statin therapy and the risk for diabetes among adult women: do the benefits outweigh the risk? , 2013, Therapeutic advances in cardiovascular disease.

[11]  P. Gasparini,et al.  Age- And Sex-Related Variations in Platelet Count in Italy: A Proposal of Reference Ranges Based on 40987 Subjects' Data , 2013, PloS one.

[12]  W. Kittikulsuth,et al.  ET‐1 actions in the kidney: evidence for sex differences , 2013, British journal of pharmacology.

[13]  T. Furukawa,et al.  Non-genomic action of sex steroid hormones and cardiac repolarization. , 2013, Biological & pharmaceutical bulletin.

[14]  Deepak L. Bhatt,et al.  Predictors of adherence to performance measures in patients with acute myocardial infarction. , 2013, The American journal of medicine.

[15]  F. Akhlaghi,et al.  Effect of Diabetes Mellitus on Pharmacokinetic and Pharmacodynamic Properties of Drugs , 2012, Clinical Pharmacokinetics.

[16]  M. Bochud,et al.  Gene–environment interactions of selected pharmacogenes in arterial hypertension , 2012, Expert review of clinical pharmacology.

[17]  P. Scheltens,et al.  Blood–brain barrier P-glycoprotein function in healthy subjects and Alzheimer's disease patients: effect of polymorphisms in the ABCB1 gene , 2012, EJNMMI Research.

[18]  W. Kostis Absolute risk reduction due to statin use according to sex. , 2012, Journal of the American College of Cardiology.

[19]  G. Burckhardt Drug transport by Organic Anion Transporters (OATs). , 2012, Pharmacology & therapeutics.

[20]  Guangping Chen,et al.  Caffeine induction of sulfotransferases in rat liver and intestine , 2012, Journal of applied toxicology : JAT.

[21]  Michael M. Wang,et al.  Myeloid Mineralocorticoid Receptor During Experimental Ischemic Stroke: Effects of Model and Sex , 2012, Journal of the American Heart Association.

[22]  F. Lenfant,et al.  Chronic estradiol treatment reduces platelet responses and protects mice from thromboembolism through the hematopoietic estrogen receptor α. , 2012, Blood.

[23]  M. Schwab,et al.  Organic Anion Transporters and Their Implications in Pharmacotherapy , 2012, Pharmacological Reviews.

[24]  H. Jaeschke,et al.  Gender-specific reduction of hepatic Mrp2 expression by high-fat diet protects female mice from ANIT toxicity. , 2012, Toxicology and applied pharmacology.

[25]  Rebecca M. Jordan-Young,et al.  Beyond a catalogue of differences: a theoretical frame and good practice guidelines for researching sex/gender in human health. , 2012, Social science & medicine.

[26]  A. Zimmer,et al.  Influence of physical exercise and gender on acetylcholinesterase and butyrylcholinesterase activity in human blood samples , 2012, International journal of environmental health research.

[27]  M. Sabatine,et al.  Platelet biology and response to antiplatelet therapy in women: implications for the development and use of antiplatelet pharmacotherapies for cardiovascular disease. , 2012, Journal of the American College of Cardiology.

[28]  Jerry Q. Cheng,et al.  Meta-analysis of statin effects in women versus men. , 2012, Journal of the American College of Cardiology.

[29]  L. Mosca Controversy and consensus about statin use: it is not about the sex. , 2012, Journal of the American College of Cardiology.

[30]  M. Stafoggia,et al.  Socio‐demographic differences in adherence to evidence‐based drug therapy after hospital discharge from acute myocardial infarction: a population‐based cohort study in Rome, Italy , 2012, Journal of clinical pharmacy and therapeutics.

[31]  M. Quinkler,et al.  Sex-specific Effects of Spironolactone on Blood Pressure in Gonadectomized Male and Female Wistar Rats , 2012, Hormone and Metabolic Research.

[32]  M. Joyner,et al.  Acute &bgr;-Adrenergic Blockade Increases Aortic Wave Reflection in Young Men and Women: Differing Mechanisms Between Sexes , 2012, Hypertension.

[33]  K. Yonkers,et al.  Gender as a Risk Factor for Adverse Events to Medications , 1995, Drugs.

[34]  V. Miller,et al.  Considerations of sex and gender differences in preclinical and clinical trials. , 2012, Handbook of experimental pharmacology.

[35]  V. Regitz-Zagrosek,et al.  Sex and gender differences in cardiovascular drug therapy. , 2012, Handbook of experimental pharmacology.

[36]  V. Regitz-Zagrosek Sex and Gender Differences in Pharmacology , 2012, Handbook of Experimental Pharmacology.

[37]  H. Palevsky,et al.  Race and sex differences in response to endothelin receptor antagonists for pulmonary arterial hypertension. , 2012, Chest.

[38]  M. Pepper,et al.  Cardiovascular pharmacogenetics. , 2012, Pharmacology & therapeutics.

[39]  F. Franconi,et al.  Sex and gender in adverse drug events, addiction, and placebo. , 2012, Handbook of experimental pharmacology.

[40]  G. Rosano,et al.  Sex differences in drug effects: interaction with sex hormones in adult life. , 2012, Handbook of experimental pharmacology.

[41]  V. Regitz-Zagrosek,et al.  Sex and gender differences in clinical medicine. , 2012, Handbook of experimental pharmacology.

[42]  E. Dworatzek,et al.  Sex differences in animal models for cardiovascular diseases and the role of estrogen. , 2012, Handbook of experimental pharmacology.

[43]  Doris A Taylor,et al.  Strategies and methods to study sex differences in cardiovascular structure and function: a guide for basic scientists , 2011, Biology of Sex Differences.

[44]  L. Chambless,et al.  Gender differences in the association between education and the incidence of cardiovascular events in Northern Italy. , 2011, European journal of public health.

[45]  M. Tsai,et al.  Quantitative shot-gun proteomics and MS-based activity assay for revealing gender differences in enzyme contents for rat liver microsome. , 2011, Journal of proteomics.

[46]  I. Spoletini,et al.  A GENS-based approach to cardiovascular pharmacology: impact on metabolism, pharmacokinetics and pharmacodynamics. , 2011, Therapeutic delivery.

[47]  X. Carné,et al.  Pharmacogenetic predictors of angiotensin-converting enzyme inhibitor-induced cough: the role of ACE, ABO, and BDKRB2 genes , 2011, Pharmacogenetics and genomics.

[48]  A. Basit,et al.  Does sex matter? The influence of gender on gastrointestinal physiology and drug delivery. , 2011, International journal of pharmaceutics.

[49]  D. Waxman,et al.  Transcriptional Profiling of Human Liver Identifies Sex-Biased Genes Associated with Polygenic Dyslipidemia and Coronary Artery Disease , 2011, PloS one.

[50]  Marko Elovainio,et al.  American Journal of Epidemiology Original Contribution Socioeconomic Differences in Cardiometabolic Factors: Social Causation or Health-related Selection? Evidence from the Whitehall Ii Cohort Study, 1991–2004 , 2022 .

[51]  M. Böhm,et al.  Efficacy and safety of olmesartan medoxomil plus amlodipine in age, gender and hypertension severity defined subgroups of hypertensive patients , 2011, Journal of Human Hypertension.

[52]  J. Potter,et al.  Determinants of Aspirin Metabolism in Healthy Men and Women: Effects of Dietary Inducers of UDP-Glucuronosyltransferases , 2011, Lifestyle Genomics.

[53]  Julie Taylor,et al.  Women's Health Research: Progress, Pitfalls, and Promise , 2011 .

[54]  R. Cardarelli,et al.  Significant differences in global genomic DNA methylation by gender and race/ethnicity in peripheral blood , 2011, Epigenetics.

[55]  J. Hayes,et al.  Mechanisms of induction of cytosolic and microsomal glutathione transferase (GST) genes by xenobiotics and pro-inflammatory agents , 2011, Drug metabolism reviews.

[56]  D. Dash,et al.  Anti-thrombotic effects of selective estrogen receptor modulator tamoxifen , 2011, Thrombosis and Haemostasis.

[57]  G. Mercuro,et al.  The effect of sex/gender on cardiovascular pharmacology. , 2011, Current pharmaceutical design.

[58]  Rowena J Dolor,et al.  Effectiveness-based guidelines for the prevention of cardiovascular disease in women--2011 update: a guideline from the American Heart Association. , 2011, Journal of the American College of Cardiology.

[59]  M. Joyner,et al.  Relationship Between Muscle Sympathetic Nerve Activity and Aortic Wave Reflection Characteristics in Young Men and Women , 2011, Hypertension.

[60]  D. Mattison,et al.  Sex Differences in Drug Disposition , 2011, Journal of biomedicine & biotechnology.

[61]  C. Anderson,et al.  Gender disparities in the assessment and management of cardiovascular risk in primary care: the AusHEART study , 2011, European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology.

[62]  M. Marino,et al.  Nutrition and human health from a sex-gender perspective. , 2011, Molecular aspects of medicine.

[63]  S. M. Vambheim,et al.  Gender Differences in Placebo Analgesia: Event-Related Potentials and Emotional Modulation , 2011, Psychosomatic medicine.

[64]  W. Dole,et al.  Influence of Body Weight and Gender on the Pharmacokinetics, Pharmacodynamics, and Antihypertensive Efficacy of Aliskiren , 2010, Journal of clinical pharmacology.

[65]  Dongxiao Sun,et al.  Sex Differences in UDP-Glucuronosyltransferase 2B17 Expression and Activity , 2010, Drug Metabolism and Disposition.

[66]  R. Collins,et al.  Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials , 2010, The Lancet.

[67]  M. Joyner,et al.  The curse of the sympathetic nervous system: are men or women more unfortunate? , 2010, The Journal of physiology.

[68]  L. Sinoway,et al.  Coronary vasoconstrictor responses are attenuated in young women as compared with age‐matched men , 2010, The Journal of physiology.

[69]  S. Nattel,et al.  Gender-related differences in ion-channel and transporter subunit expression in non-diseased human hearts. , 2010, Journal of molecular and cellular cardiology.

[70]  J. Ivanov,et al.  Cardiac-specific sympathetic activation in men and women with and without heart failure , 2010, Heart.

[71]  James Brian Byrd,et al.  Sex-dependent and race-dependent association of XPNPEP2 C-2399A polymorphism with angiotensin-converting enzyme inhibitor-associated angioedema , 2010, Pharmacogenetics and genomics.

[72]  P. Nilsson,et al.  Physicians’ gender is associated with risk factor control in patients on antihypertensive and lipid lowering treatment , 2010, Blood pressure.

[73]  S. Millasseau,et al.  Aortic wave reflection in women and men. , 2010, American journal of physiology. Heart and circulatory physiology.

[74]  R. O. Godinho,et al.  Gender-related differences in circadian rhythm of rat plasma acetyl- and butyrylcholinesterase: effects of sex hormone withdrawal. , 2010, Chemico-biological interactions.

[75]  G. Gillies,et al.  Estrogen Actions in the Brain and the Basis for Differential Action in Men and Women: A Case for Sex-Specific Medicines , 2010, Pharmacological Reviews.

[76]  D. Jacobowitz,et al.  Gender Dependence for a Subset of the Low-Abundance Signaling Proteome in Human Platelets , 2010, Human genomics and proteomics : HGP.

[77]  I. Tate Gender Differences in Management and Outcome of Acute Myocardial Infarctions Treated in 2006–2007 , 2010 .

[78]  R. Alaghehbandan,et al.  Adverse Drug Events in Adult Patients Leading to Emergency Department Visits , 2010, The Annals of pharmacotherapy.

[79]  J. Morais,et al.  The new European Medicines Agency guideline on the investigation of bioequivalence. , 2010, Basic & clinical pharmacology & toxicology.

[80]  Yasuo Ohashi,et al.  Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials , 2010, The Lancet.

[81]  M. Woodward,et al.  Effectiveness of blood pressure lowering: evidence-based comparisons between men and women , 2010, Expert review of cardiovascular therapy.

[82]  A. Curtis,et al.  Sex differences in arrhythmias , 2010, Current opinion in cardiology.

[83]  M. Quilliam,et al.  Pharmacokinetics and metabolism of diltiazem in healthy males and females following a single oral dose , 1993, European Journal of Drug Metabolism and Pharmacokinetics.

[84]  S. Nattel,et al.  Ion-channel mRNA-expression profiling: Insights into cardiac remodeling and arrhythmic substrates. , 2010, Journal of molecular and cellular cardiology.

[85]  Darrell R. Abernethy,et al.  Effect of Obesity on the Pharmacokinetics of Drugs in Humans , 2010, Clinical pharmacokinetics.

[86]  Alessandro Filippi,et al.  Adherence to Antihypertensive Medications and Cardiovascular Morbidity Among Newly Diagnosed Hypertensive Patients , 2009, Circulation.

[87]  M. Zubaid,et al.  Comparison of men and women with acute coronary syndrome in six Middle Eastern countries. , 2009, The American journal of cardiology.

[88]  A. Seeringer,et al.  Sex-specific differences in side effects of psychotropic drugs: genes or gender? , 2009, Pharmacogenomics.

[89]  E. Olshansky,et al.  Women's mental health: depression and anxiety. , 2009, The Nursing clinics of North America.

[90]  G. Onder,et al.  Heart Failure and Adverse Drug Reactions Among Hospitalized Older Adults , 2009, Clinical pharmacology and therapeutics.

[91]  Yan Jiang,et al.  Age- and Sex-Related Expression and Activity of Carboxylesterase 1 and 2 in Mouse and Human Liver , 2009, Drug Metabolism and Disposition.

[92]  M. Good,et al.  Distal upper and lower limb fractures associated with thiazolidinedione use. , 2009, The American journal of managed care.

[93]  V. Bittner Postmenopausal hormone therapy and the risk of cardiovascular disease , 2009, Expert opinion on pharmacotherapy.

[94]  D. Waxman,et al.  Sex Differences in the Expression of Hepatic Drug Metabolizing Enzymes , 2009, Molecular Pharmacology.

[95]  Salman Akhtar,et al.  Multi-locus interactions of vascular homeostasis genes in essential hypertension: a gender-based study. , 2009, Clinica chimica acta; international journal of clinical chemistry.

[96]  K. Johnell,et al.  Sex Differences in Inappropriate Drug Use: a Register-Based Study of Over 600,000 Older People , 2009, The Annals of pharmacotherapy.

[97]  M. Bebawy,et al.  Gender differences in p-glycoprotein expression and function: effects on drug disposition and outcome. , 2009, Current drug metabolism.

[98]  N. Danchin,et al.  Combined secondary prevention after hospitalization for myocardial infarction in France: analysis from a large administrative database. , 2009, Archives of cardiovascular diseases.

[99]  J. Hare,et al.  Sex‐Specific Impact of Aldosterone Receptor Antagonism on Ventricular Remodeling and Gene Expression after Myocardial Infarction , 2009, Clinical and translational science.

[100]  P. Matarrese,et al.  Cell sex: a new look at cell fate studies , 2009, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[101]  A. Parekh,et al.  Increasing participation of women in early phase clinical trials approved by the FDA. , 2009, Women's health issues : official publication of the Jacobs Institute of Women's Health.

[102]  D. Mattison,et al.  Sex Differences in Pharmacokinetics and Pharmacodynamics , 2009, Clinical pharmacokinetics.

[103]  Yibo Wang,et al.  Sex Differences in Blood Pressure Response to Antihypertensive Therapy in Chinese Patients with Hypertension , 2008, The Annals of pharmacotherapy.

[104]  W. Rogers,et al.  Trends in quality of care for patients with acute myocardial infarction in the National Registry of Myocardial Infarction from 1990 to 2006. , 2008, American heart journal.

[105]  M. Woodward,et al.  Do men and women respond differently to blood pressure-lowering treatment? Results of prospectively designed overviews of randomized trials. , 2008, European heart journal.

[106]  K. Någren,et al.  Effects of intravenous placebo with glucose expectation on human basal ganglia dopaminergic function , 2008, Synapse.

[107]  G. Remuzzi,et al.  Angiotensin converting enzyme insertion/deletion polymorphism and renoprotection in diabetic and nondiabetic nephropathies. , 2008, Clinical journal of the American Society of Nephrology : CJASN.

[108]  M. Flaten,et al.  The Roles of Physiological and Subjective Stress in the Effectiveness of a Placebo on Experimentally Induced Pain , 2008, Psychosomatic medicine.

[109]  A. Basit,et al.  Polyethylene Glycol 400 Enhances the Bioavailability of a BCS Class III Drug (Ranitidine) in Male Subjects but Not Females , 2008, Pharmaceutical Research.

[110]  A. Freyer Drug-prescribing challenges during pregnancy , 2008 .

[111]  Helen Y. Lee,et al.  Use of Secondary Prevention Drug Therapy in Patients With Acute Coronary Syndrome After Hospital Discharge , 2008, Journal of managed care pharmacy : JMCP.

[112]  J. Zbilut,et al.  Women tolerate drug therapy for coronary artery disease as well as men do, but are treated less frequently with aspirin, beta-blockers, or statins. , 2008, Gender medicine.

[113]  A. Joe,et al.  Prevention of bone loss after withdrawal of tamoxifen. , 2008, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[114]  Ping Li,et al.  Prevalence, Predictors, and Outcomes of Primary Nonadherence After Acute Myocardial Infarction , 2008, Circulation.

[115]  M. Piquette-Miller,et al.  Pharmacokinetic Studies in Pregnant Women , 2008, Clinical pharmacology and therapeutics.

[116]  C. Klaassen,et al.  Gender Differences in mRNA Expression of ATP-Binding Cassette Efflux and Bile Acid Transporters in Kidney, Liver, and Intestine of 5/6 Nephrectomized Rats , 2008, Drug Metabolism and Disposition.

[117]  S. Allender,et al.  European cardiovascular disease statistics , 2008 .

[118]  G. Seghieri,et al.  Are the available experimental models of type 2 diabetes appropriate for a gender perspective? , 2008, Pharmacological research.

[119]  V. Miller,et al.  Estrogen, inflammation, and platelet phenotype. , 2008, Gender medicine.

[120]  Tracy Budesa,et al.  Gender Influence on Perceptions of Healthy and Unhealthy Lifestyles , 2008 .

[121]  L. Arendt-Nielsen,et al.  Studying sex and gender differences in pain and analgesia: A consensus report , 2007, PAIN.

[122]  A. Dorrance,et al.  Intact female stroke-prone hypertensive rats lack responsiveness to mineralocorticoid receptor antagonists. , 2007, American journal of physiology. Regulatory, integrative and comparative physiology.

[123]  Josip Car,et al.  Trends in hospital admissions for adverse drug reactions in England: analysis of national hospital episode statistics 1998–2005 , 2007, BMC clinical pharmacology.

[124]  Rainer Schwaab,et al.  Gender specific differences in levels of DNA methylation at selected loci from human total blood: a tendency toward higher methylation levels in males , 2007, Human Genetics.

[125]  J. Schwartz The Current State of Knowledge on Age, Sex, and Their Interactions on Clinical Pharmacology , 2007, Clinical pharmacology and therapeutics.

[126]  J. Hancox,et al.  Recent advances in understanding sex differences in cardiac repolarization. , 2007, Progress in biophysics and molecular biology.

[127]  E. Vittinghoff,et al.  Effect of genetic variations in platelet glycoproteins Ibalpha and VI on the risk for coronary heart disease events in postmenopausal women taking hormone therapy. , 2007, Blood.

[128]  V. Cuomo,et al.  Gender differences in drug responses. , 2007, Pharmacological research.

[129]  C. Klaassen,et al.  Tissue- and Gender-Specific mRNA Expression of UDP-Glucuronosyltransferases (UGTs) in Mice , 2007, Drug Metabolism and Disposition.

[130]  S. Sadeghian,et al.  The effect of gender on the pharmacokinetics of verapamil and norverapamil in human , 2006, Biopharmaceutics & drug disposition.

[131]  T. Saikawa,et al.  Influence of Menstrual Cycle on QT Interval Dynamics , 2006, Pacing and clinical electrophysiology : PACE.

[132]  Christina N. Lessov-Schlaggar,et al.  Female sex and oral contraceptive use accelerate nicotine metabolism , 2006, Clinical pharmacology and therapeutics.

[133]  Silvia G Priori,et al.  Cardiovascular diseases in women: a statement from the policy conference of the European Society of Cardiology. , 2006, European heart journal.

[134]  S. Wright,et al.  Sex Differences in the mRNA, Protein, and Functional Expression of Organic Anion Transporter (Oat) 1, Oat3, and Organic Cation Transporter (Oct) 2 in Rabbit Renal Proximal Tubules , 2006, Journal of Pharmacology and Experimental Therapeutics.

[135]  Arturas Petronis,et al.  Complex disease, gender and epigenetics , 2006, Annals of medicine.

[136]  L. Becquemont,et al.  Pharmacogénétique et variabilité inter individuelle de la réponse aux traitements : l’exemple du Cytochrome P-450 2C9 et des anticoagulants coumariniques. , 2006 .

[137]  D. Vaughan,et al.  Angiotensin-Converting Enzyme Inhibition Increases Basal Vascular Tissue Plasminogen Activator Release in Women But Not in Men , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[138]  P. Bray,et al.  Aggregometry detects platelet hyperreactivity in healthy individuals. , 2005, Blood.

[139]  H. Friess,et al.  Gender‐specific expression of liver organic anion transporters in rat , 2005, European journal of clinical investigation.

[140]  M. Walton,et al.  Contraceptive Choices: Is the Future with Men? , 2005, Women's health.

[141]  A. Enomoto,et al.  Roles of organic anion transporters (OATs) and a urate transporter (URAT1) in the pathophysiology of human disease , 2005, Clinical and Experimental Nephrology.

[142]  G. Baumann,et al.  Female-specific aspects in the pharmacotherapy of chronic cardiovascular diseases. , 2005, European heart journal.

[143]  R. Karas,et al.  Molecular and Cellular Basis of Cardiovascular Gender Differences , 2005, Science.

[144]  F. Vallée,et al.  Assessment of sex differences in pharmacokinetics and pharmacodynamics of amlodipine in a bioequivalence study. , 2005, Pharmacological research.

[145]  A. V. van Kuilenburg,et al.  Pyrimidine Degradation Defects and Severe 5‐Fluorouracil Toxicity , 2004, Nucleosides, nucleotides & nucleic acids.

[146]  K. Carroll,et al.  The effects of gender, age, ethnicity, and liver cirrhosis on cytochrome P450 enzyme activity in human liver microsomes and inducibility in cultured human hepatocytes. , 2004, Toxicology and applied pharmacology.

[147]  M. Pirmohamed,et al.  Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients , 2004, BMJ : British Medical Journal.

[148]  R. Paoletti,et al.  Safety of Statins: Focus on Clinical Pharmacokinetics and Drug Interactions , 2004, Circulation.

[149]  J. Murabito,et al.  Relations of Serum Aldosterone to Cardiac Structure: Gender-Related Differences in the Framingham Heart Study , 2004, Hypertension.

[150]  D. Duprez Is the female heart more sensitive to aldosterone for early remodeling? , 2004, Hypertension.

[151]  Charles Antzelevitch,et al.  Cellular and ionic basis for the sex-related difference in the manifestation of the Brugada syndrome and progressive conduction disease phenotypes. , 2003, Journal of electrocardiology.

[152]  L. Leinwand,et al.  Sex is a potent modifier of the cardiovascular system. , 2003, The Journal of clinical investigation.

[153]  B. Pitt,et al.  Eplerenone , a Selective Aldosterone Blocker , in Patients with Left Ventricular Dysfunction after Myocardial Infarction , 2003 .

[154]  H. Lee,et al.  Gender Differences in the Membrane Transport of Endogenous and Exogenous Compounds , 2003, Pharmacological Reviews.

[155]  Paul G Shekelle,et al.  Efficacy of angiotensin-converting enzyme inhibitors and beta-blockers in the management of left ventricular systolic dysfunction according to race, gender, and diabetic status: a meta-analysis of major clinical trials. , 2003, Journal of the American College of Cardiology.

[156]  Guangping Chen,et al.  Tamoxifen induction of aryl sulfotransferase and hydroxysteroid sulfotransferase in male and female rat liver and intestine. , 2003, Drug metabolism and disposition: the biological fate of chemicals.

[157]  B. Pitt,et al.  Eplerenone, a Selective Aldosterone Blocker, in Patients with Left Ventricular Dysfunction after Myocardial Infarction , 2003 .

[158]  C. Reid,et al.  A comparison of outcomes with angiotensin-converting--enzyme inhibitors and diuretics for hypertension in the elderly. , 2003, The New England journal of medicine.

[159]  L. Becker,et al.  Platelet hyperreactivity in women from families with premature atherosclerosis. , 2003, Journal of the American Medical Women's Association.

[160]  Kazuhiro Yoshida,et al.  Gender differences in the dihydropyrimidine dehydrogenase expression of colorectal cancers. , 2002, Cancer letters.

[161]  Javed Butler,et al.  Outpatient adherence to beta-blocker therapy after acute myocardial infarction. , 2002, Journal of the American College of Cardiology.

[162]  E. Boerwinkle,et al.  Interacting effects of gender and genotype on blood pressure response to hydrochlorothiazide. , 2002, Kidney international.

[163]  Andrew C. Zygmunt,et al.  Ionic and Cellular Basis for the Predominance of the Brugada Syndrome Phenotype in Males , 2002, Circulation.

[164]  H. Melhus,et al.  The CYP2C9 genotype predicts the blood pressure response to irbesartan: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs Atenolol (SILVHIA) trial , 2002, Journal of hypertension.

[165]  Ning Li,et al.  Tissue expression, ontogeny, and inducibility of rat organic anion transporting polypeptide 4. , 2002, The Journal of pharmacology and experimental therapeutics.

[166]  S. Choudhuri,et al.  Gender-specific and developmental influences on the expression of rat organic anion transporters. , 2002, The Journal of pharmacology and experimental therapeutics.

[167]  R. Blumenthal,et al.  Interaction of hemostatic genetics with hormone therapy: new insights to explain arterial thrombosis in postmenopausal women. , 2002, Chest.

[168]  W. Koch,et al.  Male and female mice overexpressing the β2-adrenergic receptor exhibit differences in ischemia/reperfusion injury: Role of nitric oxide , 2002 .

[169]  M. Fischer,et al.  Renin angiotensin system and gender differences in the cardiovascular system. , 2002, Cardiovascular research.

[170]  S. Oparil,et al.  Sex hormones and hypertension. , 2002, Cardiovascular research.

[171]  D. Wolbrette Gender differences in the proarrhythmic potential of QT-prolonging drugs. , 2002, Current women's health reports.

[172]  James A. Blumenthal,et al.  Depression, Heart Rate Variability, and Acute Myocardial Infarction , 2001, Circulation.

[173]  C. Stier,et al.  Pathophysiological effects of aldosterone in cardiovascular tissues , 2001, Trends in Endocrinology & Metabolism.

[174]  T. Kocarek,et al.  Sex-dependent regulation by dexamethasone of murine hydroxysteroid sulfotransferase gene expression. , 2001, Toxicology letters.

[175]  J. Thom,et al.  The influence of menstrual cycle phase on skeletal muscle contractile characteristics in humans , 2001, The Journal of physiology.

[176]  M. Drici,et al.  Is Gender a Risk Factor for Adverse Drug Reactions? , 2001, Drug safety.

[177]  V. Miller,et al.  Gender-related differences in proliferative responses of vascular smooth muscle cells to endothelin-1. , 2001, Endothelium : journal of endothelial cell research.

[178]  A. Steptoe,et al.  Mental Stress Induces Transient Endothelial Dysfunction in Humans , 2000, Circulation.

[179]  R. MacCallum,et al.  Chronic Stress Modulates the Immune Response to a Pneumococcal Pneumonia Vaccine , 2000, Psychosomatic medicine.

[180]  M. Pfeffer,et al.  Sex-related differences in the use and adverse effects of angiotensin-converting enzyme inhibitors in heart failure: the study of patients intolerant of converting enzyme inhibitors registry. , 2000, The American journal of medicine.

[181]  P. Chowienczyk,et al.  Gender differences in sensitivity to adrenergic agonists of forearm resistance vasculature. , 2000, Journal of the American College of Cardiology.

[182]  J. Schwartz,et al.  Faster clearance of sustained release verapamil in men versus women: Continuing observations on sex‐specific differences after oral administration of verapamil , 2000, Clinical pharmacology and therapeutics.

[183]  P. Bray Platelet glycoprotein polymorphisms as risk factors for thrombosis , 2000, Current opinion in hematology.

[184]  G. Ness,et al.  Feedback and Hormonal Regulation of Hepatic 3-Hydroxy-3-Methylglutaryl Coenzyme a Reductase: The Concept of Cholesterol Buffering Capacity (44508) , 2000 .

[185]  A. Zanchetti,et al.  Influence of gender and age on preventing cardiovascular disease by antihypertensive treatment and acetylsalicylic acid. The HOT study , 2000 .

[186]  C. Moser,et al.  Prospective Analysis after Coronary-artery Bypass Grafting: Platelet GP IIIa Polymorphism (HPA-1b /PlA2) Is a Risk Factor for Bypass Occlusion, Myocardial Infarction, and Death , 2000, Thrombosis and Haemostasis.

[187]  A. Zanchetti,et al.  Influence of gender and age on preventing cardiovascular disease by antihypertensive treatment and acetylsalicylic acid. The HOT study. Hypertension Optimal Treatment. , 2000, Journal of hypertension.

[188]  P. Hjemdahl,et al.  Gender-related differences in response to placebo in benzodiazepine withdrawal: a single-blind pilot study , 2000, Psychopharmacology.

[189]  G. Ness,et al.  Feedback and hormonal regulation of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase: the concept of cholesterol buffering capacity. , 2000, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[190]  Michael F. Wilson,et al.  Gender‐related effects on metoprolol pharmacokinetics and pharmacodynamics in healthy volunteers , 1999, Clinical pharmacology and therapeutics.

[191]  B. Pitt,et al.  The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. , 1999, The New England journal of medicine.

[192]  R. Mann,et al.  Cough and angiotensin II receptor antagonists: cause or confounding? , 1999, British journal of clinical pharmacology.

[193]  G. L. Kedderis,et al.  Sex-dependent metabolism of xenobiotics. , 1998, Drug metabolism reviews.

[194]  P. Bray,et al.  Gender Differences in Platelet GPIIb-IIIa Activation , 1997, Thrombosis and Haemostasis.

[195]  P. Mills,et al.  The effects of the menstrual cycle, race, and gender on adrenergic receptors and agonists , 1996, Clinical pharmacology and therapeutics.

[196]  J. Weiss,et al.  A polymorphism of a platelet glycoprotein receptor as an inherited risk factor for coronary thrombosis. , 1996, The New England journal of medicine.

[197]  R. Kloner,et al.  Sex- and age-related antihypertensive effects of amlodipine , 1996 .

[198]  R. Kloner,et al.  Sex- and age-related antihypertensive effects of amlodipine. The Amlodipine Cardiovascular Community Trial Study Group. , 1996, The American journal of cardiology.

[199]  T. Powles,et al.  Effect of tamoxifen on bone mineral density measured by dual-energy x-ray absorptiometry in healthy premenopausal and postmenopausal women. , 1996, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[200]  G. Klassen,et al.  Gender Differences in Exercise and Recovery Blood Pressure Responses in Normal Volunteers Given Diltiazem , 1995, Journal of clinical pharmacology.

[201]  E. Schuetz,et al.  Interindividual variation in expression of P-glycoprotein in normal human liver and secondary hepatic neoplasms. , 1995, The Journal of pharmacology and experimental therapeutics.

[202]  J. Longstreth,et al.  Age and gender related changes in stereoselective pharmacokinetics and pharmacodynamics of verapamil and norverapamil. , 1995, British journal of clinical pharmacology.

[203]  M. Barbanoj,et al.  Gender related pharmacokinetics of diltiazem in healthy subjects. , 1995, International journal of clinical pharmacology and therapeutics.

[204]  B. Lipworth,et al.  Influence of sex-steroid hormones on the regulation of lymphocyte beta 2-adrenoceptors during the menstrual cycle. , 1994, British journal of clinical pharmacology.

[205]  J. Muller,et al.  Triggers, acute risk factors and vulnerable plaques: the lexicon of a new frontier. , 1994, Journal of the American College of Cardiology.

[206]  F. Dove Drug-induced lupus , 1982 .

[207]  W. Inman,et al.  Clinical profile of angioedema associated with angiotensin converting-enzyme inhibition. , 1988, JAMA.

[208]  K. Dickstein,et al.  Clinical pharmacokinetics in heart failure. An updated review. , 1988, Clinical pharmacokinetics.

[209]  T. Dembroski,et al.  Extent of coronary atherosclerosis, type A behavior, and cardiovascular response to social interaction. , 1981, Psychophysiology.

[210]  P. Ramwell,et al.  Sex and age differences in human platelet aggregation , 1975, Nature.

[211]  B. Brodie,et al.  Species, strain and sex differences in metabolism of hexobarbitone, amidopyrine, antipyrine and aniline , 1958 .

[212]  D. H. Barron,et al.  THE USE OF SODIUM AMYTAL IN THE PRODUCTION OF ANESTHESIA IN THE RAT , 1932 .