A comprehensive quantitative and qualitative evaluation of extrapolation of intravenous pharmacokinetic parameters from rat, dog, and monkey to humans. I. Clearance.

This study was conducted to comprehensively survey the available literature on intravenous pharmacokinetic parameters in the rat, dog, monkey, and human, and to compare common methods for extrapolation of clearance, to identify the most appropriate species to use in pharmacokinetic lead optimization, and to ascertain whether adequate prospective measures of predictive success are currently available. One hundred three nonpeptide xenobiotics were identified with intravenous pharmacokinetic data in rat, dog, monkey, and human; both body weight- and hepatic blood flow-based methods were used for scaling of clearance. Allometric scaling approaches, particularly those using data from only two of the preclinical species, were less successful at predicting human clearance than methods based on clearance as a set fraction of liver blood flow from an individual species. Furthermore, commonly used prospective measures of allometric scaling success, including correlation coefficient and allometric exponent, failed to discriminate between successful and failed allometric predictions. In all instances, the monkey tended to provide the most qualitatively and quantitatively accurate predictions of human clearance and also afforded the least biased predictions compared with other species. Additionally, the availability of data from both common nonrodent species (dog and monkey) did not ensure enhanced predictive quality compared with having only monkey data. The observations in this investigation have major implications for pharmacokinetic lead optimization and for prediction of human clearance from in vivo preclinical data and support the continued use of nonhuman primates in preclinical pharmacokinetics.

[1]  R. Kato,et al.  Disposition and enterohepatic circulation of diclofenac in dogs. , 1980, Arzneimittel-Forschung.

[2]  Roger L. Black,et al.  Goodman and Gilman's The Pharmacological Basis of Therapeutics , 1991 .

[3]  F. Balis,et al.  Effect of Fluconazole on the Pharmacokinetics of Doxorubicin in Nonhuman Primates , 2000, Antimicrobial Agents and Chemotherapy.

[4]  Paul W. Buehler,et al.  Comparison of Oral Absorption and Bioavailability of Drugs Between Monkey and Human , 2002, Pharmaceutical Research.

[5]  M. Root,et al.  Comparative pharmacokinetics of vindesine, vincristine and vinblastine in patients with cancer. , 1980, Cancer treatment reviews.

[6]  Y. Sawada,et al.  Prediction of the pharmacokinetics of cefodizime and cefotetan in humans from pharmacokinetic parameters in animals. , 1990, Journal of pharmacobio-dynamics.

[7]  F. Balis,et al.  Cerebrospinal fluid and plasma pharmacokinetics of morphine infusions in pediatrie cancer patients and rhesus monkeys , 1987, Pain.

[8]  D J Rance,et al.  The prediction of human pharmacokinetic parameters from preclinical and in vitro metabolism data. , 1997, The Journal of pharmacology and experimental therapeutics.

[9]  W. Krause,et al.  Pharmacokinetics and biotransformation of the prostacyclin analogue, ZK 36 374, in the monkey (Macaca fascicularis). , 1983, Prostaglandins, leukotrienes, and medicine.

[10]  K. Bischoff,et al.  Methotrexate pharmacokinetics. , 1971, Journal of pharmaceutical sciences.

[11]  F. Tse,et al.  Disposition of fluvastatin, an inhibitor of HMG-COA reductase, in mouse, rat, dog, and monkey. , 1990, Biopharmaceutics & drug disposition.

[12]  D. Margolskee,et al.  Dose-dependent kinetics of the enantiomers of MK-571, an LTD4-receptor antagonist , 2005, European Journal of Clinical Pharmacology.

[13]  R. Ings,et al.  Interspecies scaling and comparisons in drug development and toxicokinetics. , 1990, Xenobiotica; the fate of foreign compounds in biological systems.

[14]  J. Cullen,et al.  Antipyrine and caffeine dispositions in clinically normal dogs and dogs with progressive liver disease. , 1994, American journal of veterinary research.

[15]  W. H. Barr,et al.  Cocaine inhalation in the rat: pharmacokinetics and cardiovascular response. , 1991, The Journal of pharmacology and experimental therapeutics.

[16]  J. D. Baggot,et al.  Pharmacokinetics and cardiopulmonary effects of fentanyl in isoflurane-anesthetized rhesus monkeys (Macaca mulatta). , 2000, American journal of veterinary research.

[17]  G. Drusano,et al.  Dose ranging study and constant infusion evaluation of ciprofloxacin , 1986, Antimicrobial Agents and Chemotherapy.

[18]  E. Swabb,et al.  Prediction of aztreonam pharmacokinetics in humans based on data from animals , 1983, Journal of Pharmacokinetics and Biopharmaceutics.

[19]  J. Balian,et al.  Interspecies scaling: a comparative study for the prediction of clearance and volume using two or more than two species. , 1996, Life sciences.

[20]  H. Yamamoto,et al.  Effects of adrenalectomy on pharmacokinetics and antinociceptive activity of morphine in rats. , 1988, Japanese journal of pharmacology.

[21]  H. El-kashef,et al.  Effect of streptozotocin-induced hyperglycaemia on intravenous pharmacokinetics and acute cardiotoxicity of doxorubicin in rats. , 2000, Pharmacological research.

[22]  John F. Young,et al.  Interspecies comparison of in vivo caffeine pharmacokinetics in man, monkey, rabbit, rat, and mouse. , 1984, Drug metabolism reviews.

[23]  D. Campbell Can Allometric Interspecies Scaling be Used to Predict Human Kinetics? , 1994 .

[24]  J. Ilkiw,et al.  Comparative study of the pharmacokinetics of alfentanil in rabbits, sheep, and dogs. , 1991, American journal of veterinary research.

[25]  M. Cayen,et al.  Species differences in the pharmacokinetics of recainam, a new anti‐arrhythmic drug , 1990, Biopharmaceutics & drug disposition.

[26]  K. Goa,et al.  Iloprost. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in peripheral vascular disease, myocardial ischaemia and extracorporeal circulation procedures. , 1992, Drugs.

[27]  D. Greenblatt,et al.  Effect of propranolol on pharmacokinetics and acute electrocardiographic changes following intravenous quinidine in humans. , 1978, Pharmacology.

[28]  H. Boxenbaum,et al.  Interspecies pharmacokinetic scaling and the Dedrick plots. , 1983, The American journal of physiology.

[29]  J. Lima,et al.  Evaluation of dose-dependent pharmacokinetics of cocaethylene and cocaine in conscious dogs. , 1997, Life sciences.

[30]  J. Grygiel,et al.  Pharmacokinetics of tiazofurin in the plasma and cerebrospinal fluid of rhesus monkeys. , 1985, Cancer research.

[31]  R. Fruncillo,et al.  Pharmacokinetics of pentobarbital, quinidine, lidocaine, and theophylline in the thermally injured rat. , 1984, Journal of pharmaceutical sciences.

[32]  R. H. Reuning,et al.  Disposition and pharmacokinetics of naltrexone after intravenous and oral administration in rhesus monkeys. , 1989, Drug metabolism and disposition: the biological fate of chemicals.

[33]  L. Sansom,et al.  Human pharmacokinetics of tiludronate. , 1995, Bone.

[34]  D. Benziger,et al.  Metabolism and disposition of amifloxacin in laboratory animals , 1985, Antimicrobial Agents and Chemotherapy.

[35]  E. Vesell,et al.  Pharmacokinetics of nicotine and 12 metabolites in the rat. Application of a new radiometric high performance liquid chromatography assay. , 1988, Drug metabolism and disposition: the biological fate of chemicals.

[36]  H. Lode Pharmacokinetics and clinical results of parenterally administered new quinolones in humans. , 1989, Reviews of infectious diseases.

[37]  D. Pettibone,et al.  The Role of Drug Metabolism in Drug Discovery: A Case Study in the Selection of an Oxytocin Receptor Antagonist for Development , 1995, Toxicologic pathology.

[38]  G. Preston,et al.  First Time in Human for GV196771: Interspecies Scaling Applied on Dose Selection , 1999, Journal of clinical pharmacology.

[39]  R. Levy,et al.  Pharmacokinetic profile of valproic acid in rhesus monkeys following single bolus and constant rate intravenous administrations. , 1980, Therapie.

[40]  J. Balian,et al.  Interspecies scaling: predicting clearance of drugs in humans. Three different approaches. , 1996, Xenobiotica; the fate of foreign compounds in biological systems.

[41]  N. Ishikawa,et al.  Pharmacokinetics of a new quinolone, AM-833, in mice, rats, rabbits, dogs, and monkeys , 1986, Antimicrobial Agents and Chemotherapy.

[42]  E. Hussey,et al.  Interspecies Scaling and Pharmacokinetic Parameters of 3TC in Humans , 1994, Journal of clinical pharmacology.

[43]  T. Lavé,et al.  Animal Pharmacokinetics and Interspecies Scaling from Animals to Man of Lamifiban, a New Platelet Aggregation Inhibitor , 1996, The Journal of pharmacy and pharmacology.

[44]  D. Shand,et al.  The disposition of propranolol. 3. Decreased half-life and volume of distribution as a result of plasma binding in man, monkey, dog and rat. , 1973, The Journal of pharmacology and experimental therapeutics.

[45]  So H. Kim,et al.  Interspecies pharmacokinetic scaling of a new carbapenem, DA‐1131, in mice, rats, rabbits and dogs, and prediction of human pharmacokinetics , 1998, Biopharmaceutics & drug disposition.

[46]  M. Delp,et al.  Physiological Parameter Values for Physiologically Based Pharmacokinetic Models , 1997, Toxicology and industrial health.

[47]  K. Melmon,et al.  DISPOSITION KINETICS OF LIDOCAINE IN NORMAL SUBJECTS * , 1971, Annals of the New York Academy of Sciences.

[48]  M. McLean Clinical pharmacokinetics of gabapentin , 1994, Neurology.

[49]  P. Conlon,et al.  Pharmacokinetics of ketorolac after intravenous and oral single dose administration in dogs. , 1999, Journal of veterinary pharmacology and therapeutics.

[50]  T. Horie,et al.  In vivo and in vitro trimethadione oxidation activity of the liver from various animal species including mouse, hamster, rat, rabbit, dog, monkey and human , 1999, Human & experimental toxicology.

[51]  Baggot Jd Application of interspecies scaling to the bispyridinium oxime HI-6. , 1994 .

[52]  A. White,et al.  Bactericidal effects of amoxycillin/clavulanic acid and ticarcillin/clavulanic acid in in-vitro kinetic models. , 1985, The Journal of antimicrobial chemotherapy.

[53]  P. Held,et al.  931-115 Phase I Studies on Inogatran, a New Selective Thrombin Inhibitor , 1995 .

[54]  K. Coleman,et al.  Pharmacokinetic studies and renal dehydropeptidase stability of the new beta-lactamase inhibitor BRL 42715 in animals , 1991, Antimicrobial Agents and Chemotherapy.

[55]  N. Kaplowitz,et al.  Metabolic clearance of furosemide in the rat. , 1977, The Journal of pharmacology and experimental therapeutics.

[56]  Koichi Takahashi,et al.  Effect of Age on the Gastrointestinal Absorption of Acyclovir in Rats , 1991, The Journal of pharmacy and pharmacology.

[57]  G. Robbie,et al.  Correlation of Plasma Clearance of 54 Extensively Metabolized Drugs Between Humans and Rats: Mean Allometric Coefficient of 0.66 , 1998, Pharmaceutical Research.

[58]  B. Duce,et al.  Oral absorption and disposition kinetics of lidocaine hydrochloride in dogs. , 1970, The Journal of pharmacology and experimental therapeutics.

[59]  J. Hsieh,et al.  Interspecies differences in stereoselective protein binding and clearance of MK-571. , 1990, Drug metabolism and disposition: the biological fate of chemicals.

[60]  W. Jusko,et al.  Nonlinear pharmacokinetics and interconversion of prednisolone and prednisone in rats , 1990, Journal of Pharmacokinetics and Biopharmaceutics.

[61]  P. Marrari,et al.  Pharmacokinetics of iododoxorubicin in the rat, dog, and monkey. , 1991, Drug metabolism and disposition: the biological fate of chemicals.

[62]  I Mahmood,et al.  Allometric issues in drug development. , 1999, Journal of pharmaceutical sciences.

[63]  S. Cherkofsky 1-Aminocyclopropanecarboxylic acid: mouse to man interspecies pharmacokinetic comparisons and allometric relationships. , 1995, Journal of pharmaceutical sciences.

[64]  U. Klotz,et al.  The effect of cirrhosis on the disposition and elimination of meperidine in man , 1974 .

[65]  D. Türck,et al.  Disposition of gabapentin (neurontin) in mice, rats, dogs, and monkeys. , 1995, Drug metabolism and disposition: the biological fate of chemicals.

[66]  D. Jung,et al.  Pharmacokinetics of ketorolac tromethamine in humans after intravenous, intramuscular and oral administration , 2004, European Journal of Clinical Pharmacology.

[67]  M. Mandelli,et al.  Pharmacokinetics and tolerance of a new penem antibiotic, FCE 22101, in healthy volunteers after a single intravenous dose , 2004, European Journal of Clinical Pharmacology.

[68]  I Mahmood,et al.  Interspecies scaling of renally secreted drugs. , 1998, Life sciences.

[69]  G. Harper,et al.  The disposition and metabolism of tiazofurin in rodents, rabbits, and dogs. , 1984, Drug metabolism and disposition: the biological fate of chemicals.

[70]  G. S. Duthu Interspecies correlation of the pharmacokinetics of erythromycin, oleandomycin, and tylosin. , 1985, Journal of pharmaceutical sciences.

[71]  M. Williams,et al.  Interspecies comparison of acivicin pharmacokinetics. , 1988, Drug metabolism and disposition: the biological fate of chemicals.

[72]  Y. Sugiyama,et al.  Prediction of the disposition of nine weakly acidic and six weakly basic drugs in humans from pharmacokinetic parameters in rats , 1985, Journal of Pharmacokinetics and Biopharmaceutics.

[73]  K. Fredricson Overø Kinetics of citalopram in test animals; drug exposure in safety studies. , 1982, Progress in neuro-psychopharmacology & biological psychiatry.

[74]  B. D. Anderson,et al.  Uptake kinetics of 2',3'-dideoxyinosine into brain and cerebrospinal fluid of rats: intravenous infusion studies. , 1990, The Journal of pharmacology and experimental therapeutics.

[75]  A. Atkinson,et al.  Amphotericin B Pharmacokinetics in Humans , 1978, Antimicrobial Agents and Chemotherapy.

[76]  M. Sáez,et al.  Disposition of ciprofloxacin following intravenous administration in dogs. , 1994, Journal of veterinary pharmacology and therapeutics.

[77]  A. Breckenridge,et al.  Drug-protein conjugates--IV. The effect of acute renal failure on the disposition of [14C]captopril in the rat. , 1983, Biochemical pharmacology.

[78]  Y. Sugiyama,et al.  Pharmacokinetics of CPT-11 in rhesus monkeys , 1997, Cancer Chemotherapy and Pharmacology.

[79]  G. Wagner,et al.  Pharmacokinetics and interspecies scaling of a novel VEGF receptor inhibitor, SU5416 , 2001, The Journal of pharmacy and pharmacology.

[80]  H. Tokiwa,et al.  Prediction of human pharmacokinetics of panipenem-betamipron, a new carbapenem, from animal data , 1992, Antimicrobial Agents and Chemotherapy.

[81]  C. Spurr,et al.  Pharmacokinetics of vincristine, vinblastine, and vindesine in rhesus monkeys , 2004, Cancer Chemotherapy and Pharmacology.

[82]  A. Hayes Principles and methods of toxicology , 1982 .

[83]  S. Liao,et al.  Pharmacokinetics and bioavailability of zidovudine in humans. , 1988, The American journal of medicine.

[84]  M. Hümpel,et al.  Investigations of pharmacokinetics of ethinyloestradiol to specific consideration of a possible first-pass effect in women. , 1979, Contraception.

[85]  M. Chaplin,et al.  Absorption, distribution, metabolism, and excretion of naproxen in various laboratory animals and human subjects. , 1972, Journal of pharmaceutical sciences.

[86]  F. Balis,et al.  Cerebrospinal fluid and plasma pharmacokinetics of morphine infusions in pediatric cancer patients and rhesus monkeys. , 1987, Pain.

[87]  J. Gallo,et al.  High-performance liquid chromatographic determination of the calcium channel blocker nimodipine in monkey plasma. , 1992, Journal of chromatography.

[88]  Harold Boxenbaum,et al.  Interspecies scaling, allometry, physiological time, and the ground plan of pharmacokinetics , 1982, Journal of Pharmacokinetics and Biopharmaceutics.

[89]  Franco Lombardo,et al.  Prediction of volume of distribution values in humans for neutral and basic drugs using physicochemical measurements and plasma protein binding data. , 2002, Journal of medicinal chemistry.

[90]  R. Branch,et al.  The influence of indomethacin on the pharmacokinetics, diuretic response and hemodynamics of furosemide in the dog. , 1978, The Journal of pharmacology and experimental therapeutics.

[91]  McLean Mj Clinical pharmacokinetics of gabapentin. , 1994 .

[92]  S. E. el Dareer,et al.  Distribution and metabolism of prednisone in mice, dogs, and monkeys. , 1977, Cancer treatment reports.

[93]  M. Hayashi,et al.  Species differences in oral bioavailability of methotrexate between rats and monkeys. , 2000, Biological & pharmaceutical bulletin.

[94]  B. Phillips,et al.  Influence of the cardioprotective agent dexrazoxane on doxorubicin pharmacokinetics in the dog , 2004, Cancer Chemotherapy and Pharmacology.

[95]  Interspecies Scaling of Tebufelone Pharmacokinetic Data and Application to Preclinical Toxicology , 1995, Pharmaceutical Research.

[96]  W. Löscher,et al.  Clinical pharmacokinetics of phenytoin in the dog: a reevaluation. , 1980, American journal of veterinary research.

[97]  Tim Morris,et al.  Physiological Parameters in Laboratory Animals and Humans , 1993, Pharmaceutical Research.

[98]  J. M. Shaw,et al.  Disposition of [14C]aztreonam in rats, dogs, and monkeys , 1984, Antimicrobial Agents and Chemotherapy.

[99]  A. Karim,et al.  Pharmacokinetics and steady-state myocardial uptake of disopyramide in the dog. , 1978, Drug metabolism and disposition: the biological fate of chemicals.

[100]  U. Täuber,et al.  Half-lives in plasma and bioavailability of ethinylestradiol in laboratory animals. , 1986, Arzneimittel-Forschung.

[101]  J. M. Shaw,et al.  Pharmacokinetics of captopril in dogs and monkeys. , 1981, Journal of pharmaceutical sciences.

[102]  E. W. Swenson,et al.  Flunisolide metabolism and dynamics of a metabolite , 1980, Clinical pharmacology and therapeutics.

[103]  J. Meyer,et al.  Animal pharmacokinetics and interspecies scaling of Ro 25-6833 and related (lactamylvinyl)cephalosporins. , 1998, Journal of pharmaceutical sciences.

[104]  W. Löscher Serum protein binding and pharmacokinetics of valproate in man, dog, rat and mouse. , 1978, The Journal of pharmacology and experimental therapeutics.

[105]  K. Bischoff,et al.  Interspecies correlation of plasma concentration history of methotrexate (NSC-740). , 1970, Cancer chemotherapy reports.

[106]  S. Sisenwine,et al.  Plasma concentrations and urinary excretion of isosorbide dinitrate and its metabolites in the dog. , 1971, The Journal of pharmacology and experimental therapeutics.

[107]  E. Eschenhof [Studies on the disposition of the anticonvulsant clonazepam in the organisms of rat, dog, and man]. , 1973, Arzneimittel-Forschung.

[108]  B. R. Kuhnert,et al.  Disposition of Intrapartum Narcotic Analgesics in Monkeys , 1988, Anesthesia and analgesia.

[109]  Keith W Ward,et al.  A comprehensive quantitative and qualitative evaluation of extrapolation of intravenous pharmacokinetic parameters from rat, dog, and monkey to humans. II. Volume of distribution and mean residence time. , 2004, Drug metabolism and disposition: the biological fate of chemicals.

[110]  H Boxenbaum,et al.  Interspecies pharmacokinetic scaling and the evolutionary-comparative paradigm. , 1984, Drug metabolism reviews.

[111]  Hyunyoung Jeong,et al.  Evaluation of Using Dog as an Animal Model to Study the Fraction of Oral Dose Absorbed of 43 Drugs in Humans , 2000, Pharmaceutical Research.

[112]  C. K. Chu,et al.  Pharmacokinetics and saturable renal tubular secretion of zidovudine in rats. , 1989, Journal of pharmaceutical sciences.

[113]  J. Salmon,et al.  Pharmacokinetics and metabolism of moxestrol in animals--rat, dog and monkey. , 1983, Journal of Steroid Biochemistry.

[114]  P. Hoeprich,et al.  Comparative Pharmacology of Amphotericin B and Amphotericin B Methyl Ester in the Non-Human Primate, Macaca mulatta , 1977, Antimicrobial Agents and Chemotherapy.

[115]  J. Kutcher,et al.  Pharmacological studies with vinblastine in the dog. , 1975, Cancer research.

[116]  T. Taylor,et al.  Pharmacokinetics of isosorbide dinitrate after intravenous infusion in human subjects , 1980, Biopharmaceutics & drug disposition.

[117]  C. Weber,et al.  Hemodynamics, biochemical effects, and pharmacokinetics of the renin inhibitor remikiren in healthy human subjects , 1993, Clinical pharmacology and therapeutics.

[118]  H. Fung,et al.  Pharmacokinetic/pharmacodynamic relationship of the duration of vasodilating action of organic mononitrates in rats. , 1992, Journal of Pharmacology and Experimental Therapeutics.

[119]  J. Miller,et al.  Comparative pharmacokinetics of frusemide in female rhesus monkeys, cynomolgus monkeys and baboons. , 1982, Comparative biochemistry and physiology. C: Comparative pharmacology.

[120]  K. Strein,et al.  Pharmacokinetic aspects of isosorbide-5-mononitrate in dogs. , 1984, The Journal of pharmacology and experimental therapeutics.

[121]  A. Nitenberg,et al.  Reversibility by dipyridamole of thallium-201 myocardial scan defects in patients with sarcoidosis. , 1988, The American journal of medicine.

[122]  N. Benowitz,et al.  Lidocaine disposition kinetics in monkey and man; I. Prediction by a perfusion model , 1974, Clinical pharmacology and therapeutics.

[123]  R. C. Chou,et al.  Pharmacokinetics of remikiren, a potent orally active inhibitor of human renin, in rat, dog and primates. , 1996, Xenobiotica; the fate of foreign compounds in biological systems.

[124]  P. Sanwald-Ducray,et al.  Prediction of the pharmacokinetic parameters of reduced-dolasetron in man using in vitro-in vivo and interspecies allometric scaling. , 1997, Xenobiotica; the fate of foreign compounds in biological systems.

[125]  M. Nishida,et al.  Pharmacokinetics of ceftizoxime in animals after parenteral dosing , 1980, Antimicrobial Agents and Chemotherapy.

[126]  K. Sasahara,et al.  Dosage form design for improvement of bioavailability of levodopa IV: Possible causes of low bioavailability of oral levodopa in dogs. , 1981, Journal of pharmaceutical sciences.

[127]  B. York,et al.  Interspecies comparison of the pharmacokinetics of aldose reductase inhibitors. , 1990, Drug metabolism and disposition: the biological fate of chemicals.

[128]  M. Danhof,et al.  Studies on the different metabolic pathways of antipyrine in rats: influence of phenobarbital and 3-methylcholanthrene treatment. , 1979, Xenobiotica; the fate of foreign compounds in biological systems.

[129]  L. F. Chasseaud,et al.  Isosorbide 5-mononitrate pharmacokinetics in humans. , 1981, Biopharmaceutics & drug disposition.

[130]  H. Bhargava,et al.  Pharmacodynamics and pharmacokinetics of intravenously administered morphine in spontaneously hypertensive and normotensive Wistar-Kyoto rats. , 1992, Journal of Pharmacology and Experimental Therapeutics.

[131]  J. Nutt,et al.  L‐Dopa pharmacokinetics in plasma and cisternal and lumbar cerebrospinal fluid of monkeys , 1990, Annals of neurology.

[132]  J. Mandema,et al.  Pharmacodynamic model for acute tolerance development to the electroencephalographic effects of alfentanil in the rat. , 1995, The Journal of pharmacology and experimental therapeutics.

[133]  K. Koch,et al.  Phenytoin–Valproic Acid Interaction in Rhesus Monkey , 1981, Epilepsia.

[134]  W. Kyner,et al.  Effects of ethinyl estradiol on pharmacokinetics of meperidine and pentobarbital in the rat. , 1982, The Journal of pharmacology and experimental therapeutics.

[135]  H. Matsui,et al.  Comparative pharmacokinetics of YM-13115, ceftriaxone, and ceftazidime in rats, dogs, and rhesus monkeys , 1984, Antimicrobial Agents and Chemotherapy.

[136]  F. Balis,et al.  Pharmacokinetics of lamivudine and BCH-189 in plasma and cerebrospinal fluid of nonhuman primates , 1995, Antimicrobial agents and chemotherapy.

[137]  C. Scripture,et al.  Clinical Pharmacokinetics of Fluvastatin , 2001, Clinical pharmacokinetics.

[138]  D. Azarnoff,et al.  Clinical pharmacokinetics of disopyramide , 1982, Journal of Pharmacokinetics and Biopharmaceutics.

[139]  D. Loebenberg,et al.  Comparative pharmacokinetics of Sch 28191 and amphotericin B in mice, rats, dogs, and cynomolgus monkeys , 1984, Antimicrobial Agents and Chemotherapy.

[140]  R. Miller,et al.  Interaction of diclofenac and quinidine in monkeys: stimulation of diclofenac metabolism. , 1999, The Journal of pharmacology and experimental therapeutics.

[141]  S. Kaul,et al.  Pharmacokinetics of 2',3'-dideoxyinosine (BMY-40900), a new anti-human immunodeficiency virus agent, after administration of single intravenous doses to beagle dogs , 1991, Antimicrobial Agents and Chemotherapy.

[142]  L. McCoy,et al.  Analysis of amifloxacin in plasma and urine by high-pressure liquid chromatography and intravenous pharmacokinetics in rhesus monkeys , 1985, Antimicrobial Agents and Chemotherapy.

[143]  D. Fish,et al.  Pharmacokinetics of Intravenous Trovafloxacin in Critically Ill Adults , 2000, Pharmacotherapy.

[144]  R. Portmann,et al.  Interspecies Pharmacokinetic Comparisons and Allometric Scaling of Napsagatran, a Low Molecular Weight Thrombin Inhibitor , 1999, The Journal of pharmacy and pharmacology.

[145]  R. Portmann,et al.  Single- and multiple-dose pharmacokinetics of fleroxacin, a trifluorinated quinolone, in humans , 1987, Antimicrobial Agents and Chemotherapy.

[146]  N. Benowitz,et al.  Disposition kinetics of nicotine and cotinine enantiomers in rabbits and beagle dogs. , 1988, Journal of pharmaceutical sciences.

[147]  E. Doyle,et al.  Comparative pharmacokinetics of antipyrine (phenazone) in the baboon, cynomolgus monkey and rhesus monkey. , 1981, Toxicology.

[148]  A. Somogyi,et al.  The disposition of morphine and its 3- and 6-glucuronide metabolites in humans and animals, and the importance of the metabolites to the pharmacological effects of morphine. , 1996, Drug metabolism reviews.

[149]  Ulf Bredberg,et al.  Animal pharmacokinetics of inogatran, a low‐molecular‐weight thrombin inhibitor with potential use as an antithrombotic drug , 1998, Biopharmaceutics & drug disposition.

[150]  D. Turner Influence of route of administration on metabolism of [14C]nicotine in four species. , 1975, Xenobiotica; the fate of foreign compounds in biological systems.

[151]  C. Hug,et al.  Tissue Redistribution of Fentanyl and Termination of Its Effects in Rats , 1981, Anesthesiology.

[152]  K. Pittman,et al.  Pharmacokinetics of the novel cephalosporin cefepime (BMY-28142) in rats and monkeys , 1987, Antimicrobial Agents and Chemotherapy.

[153]  J. Gallo,et al.  Pharmacokinetics of 2',3'-dideoxyinosine in monkeys , 1991, Antimicrobial Agents and Chemotherapy.

[154]  K. Ward,et al.  Preclinical pharmacokinetics and interspecies scaling of a novel vitronectin receptor antagonist. , 1999, Drug metabolism and disposition: the biological fate of chemicals.

[155]  P. Bonate,et al.  Critique of Prospective Allometric Scaling: Does the Emperor Have Clothes? , 2000, Journal of clinical pharmacology.

[156]  W. Ritschel,et al.  Meperidine pharmacokinetics following intravenous, peroral and buccal administration in beagle dogs. , 1987, Methods and findings in experimental and clinical pharmacology.

[157]  D. McClain,et al.  Dose‐independent Pharmacokinetics of Fentanyl , 1982, Anesthesiology.

[158]  Y. Sugiyama,et al.  Prediction of the disposition ofβ-lactam antibiotics in humans from pharmacokinetic parameters in animals , 1984, Journal of Pharmacokinetics and Biopharmaceutics.

[159]  D. V. Von Hoff,et al.  Phase I evaluation and pharmacokinetics of tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide, NSC 286193). , 1985, Cancer research.

[160]  J. Garrelts,et al.  The Pharmacokinetics, Safety, and Tolerance of Cefepime Administered as an Intravenous Bolus or as a Rapid Infusion , 1999, The Annals of pharmacotherapy.

[161]  F. De Smet,et al.  Aging and the pharmacokinetics and metabolism of metoprolol enantiomers in the rat. , 1993, Journal of gerontology.

[162]  K. Overø Kinetics of citalopram in test animals; drug exposure in safety studies , 1982, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[163]  R. Levy,et al.  Pharmacokinetic profile of clonazepam in rhesus monkeys. , 1978, Journal of pharmaceutical sciences.

[164]  D. E. Duggan,et al.  The effects of probenecid upon the individual components of indomethacin elimination. , 1977, The Journal of pharmacology and experimental therapeutics.

[165]  Mossad A. El Sayed Pharmacokinetics of ethosuximide in the dog. , 1978 .

[166]  E. Perucca,et al.  Pharmacokinetics of valproic acid after oral and intravenous administration , 1978 .

[167]  A G Renwick,et al.  The effect of age on the pharmacokinetics of levodopa administered alone and in the presence of carbidopa. , 1989, British journal of clinical pharmacology.

[168]  M. Hildebrand Inter-species extrapolation of pharmacokinetic data of three prostacyclin-mimetics. , 1994, Prostaglandins.

[169]  J. Sassard,et al.  Chronopharmacokinetics of indomethacin in rats. , 1987, Arzneimittel-Forschung.

[170]  G. Robbie,et al.  Elucidation of Human Amphotericin B Pharmacokinetics: Identification of a New Potential Factor Affecting Interspecies Pharmacokinetic Scaling , 1998, Pharmaceutical Research.

[171]  I. Patel,et al.  Pharmacokinetic Properties of Ethosuximide in Monkeys. I. Single‐Dose Intravenous and Oral Administration , 1975, Epilepsia.

[172]  R. Parrish,et al.  Pharmacokinetics of naloxone and naltrexone in the dog. , 1979, The Journal of pharmacology and experimental therapeutics.

[173]  J. Macgregor,et al.  Comparative physiological disposition of N-(phosphonacetyl)-L-aspartate in several animal species after intravenous and oral administration. , 1982, Cancer research.

[174]  L. Peterson,et al.  Pharmacokinetics, protein binding, and extravascular distribution of ceftizoxime in normal subjects , 1982, Antimicrobial Agents and Chemotherapy.

[175]  M. Iwaki,et al.  A pharmacokinetic model for the percutaneous absorption of indomethacin and the prediction of drug disposition kinetics. , 1989, Journal of pharmaceutical sciences.

[176]  T. Miura,et al.  Pharmacokinetic study of biapenem. , 1994 .

[177]  G. Bonadonna,et al.  Pharmacology and clinical toxicity of 4'-iodo-4'-deoxydoxorubicin: an example of successful application of pharmacokinetics to dose escalation in phase I trials. , 1990, Journal of the National Cancer Institute.

[178]  W. Hardwick,et al.  Phencyclidine pharmacokinetic scaling among species. , 1987, The Journal of pharmacology and experimental therapeutics.

[179]  E. U. Kölle,et al.  Pharmacokinetics and metabolism of gabapentin in rat, dog and man. , 1986, Arzneimittel-Forschung.

[180]  I. Påhlman,et al.  Pharmacokinetics of Susalimod, a Highly Biliary‐excreted Sulphasalazine Analogue, in Various Species. Nonpredictable Human Clearance by Allometric Scaling , 1998 .

[181]  D. Maruhn,et al.  Pharmacokinetics of nimodipine. I. Communication: absorption, concentration in plasma and excretion after single administration of [14C]nimodipine in rat, dog and monkey. , 1985, Arzneimittel-Forschung.

[182]  C. Marsden,et al.  Peripheral Pharmacokinetic Handling and Metabolism of L‐Dopa in the Rat: The Effect of Route of Administration and Carbidopa Pretreatment , 1991, The Journal of pharmacy and pharmacology.

[183]  M. S. Langley,et al.  Nimodipine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in cerebrovascular disease. , 1989, Drugs.

[184]  S. Higuchi,et al.  Comparative pharmacokinetics of nicardipine hydrochloride, a new vasodilator, in various species. , 1980, Xenobiotica; the fate of foreign compounds in biological systems.

[185]  H L Fung,et al.  Isosorbide dinitrate disposition in the rat: metabolite pharmacokinetics and interactions. , 1984, The Journal of pharmacology and experimental therapeutics.

[186]  D. A. Page,et al.  Species differences in the disposition of acyclovir. , 1982, The American journal of medicine.

[187]  F. Sarnquist,et al.  Ketorolac tromethamine absorption, distribution, metabolism, excretion, and pharmacokinetics in animals and humans. , 1987, Drug metabolism and disposition: the biological fate of chemicals.

[188]  K. Ward,et al.  SB-242235, a selective inhibitor of p38 mitogen-activated protein kinase. II: In vitro and in vivo metabolism studies and pharmacokinetic extrapolation to man , 2002, Xenobiotica; the fate of foreign compounds in biological systems.

[189]  A. Yacobi,et al.  Comparative pharmacokinetics of coumarin anticoagulants. XIV: relationship between protein binding, distribution, and elimination kinetics of warfarin in rats. , 1975, Journal of pharmaceutical sciences.

[190]  T. Izumi,et al.  Prediction of the human pharmacokinetics of troglitazone, a new and extensively metabolized antidiabetic agent, after oral administration, with an animal scale-up approach. , 1996, The Journal of pharmacology and experimental therapeutics.

[191]  R. Schinazi,et al.  Comparative pharmacokinetics and interspecies scaling of 3'-azido-3'-deoxythymidine (AZT) in several mammalian species. , 1990, Journal of pharmacobio-dynamics.

[192]  G. Levy,et al.  Comparative pharmacokinetics of coumarin anticoagulants. V. Kinetics of warfarin elimination in the rat, dog, and rhesus monkey compared to man. , 1969, Journal of pharmaceutical sciences.

[193]  M. Papich,et al.  Comparison of cefepime pharmacokinetics in neonatal foals and adult dogs. , 2001, Journal of veterinary pharmacology and therapeutics.

[194]  L. Mellett Comparative drug metabolism. , 1969, Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques.

[195]  C. T. Ueda,et al.  Concentration-time effects of quinidine disposition kinetics in rhesus monkeys. , 1977, The Journal of pharmacology and experimental therapeutics.

[196]  W. Krause,et al.  Pharmacokinetics of rolipram in the rhesus and cynomolgus monkeys, the rat and the rabbit. Studies on species differences. , 1988, Xenobiotica; the fate of foreign compounds in biological systems.

[197]  S. E. el Dareer,et al.  Distribution and metabolism of vincristine in mice, rats, dogs, and monkeys. , 1977, Cancer treatment reports.

[198]  I. Mahmood,et al.  Interspecies scaling of biliary excreted drugs. , 2002, Journal of pharmaceutical sciences.

[199]  A. Karim,et al.  Pharmacokinetics of a Novel Antiarrhythmic Drug, Actisomide , 1993, Pharmaceutical Research.

[200]  S. Moss,et al.  The disposition and metabolism of meropenem in laboratory animals and man. , 1989, The Journal of antimicrobial chemotherapy.

[201]  T. Gootz,et al.  Pharmacokinetics of trovafloxacin (CP-99,219), a new quinolone, in rats, dogs, and monkeys , 1996, Antimicrobial agents and chemotherapy.

[202]  C. Kohlsdorfer,et al.  Pharmacokinetics of the 8-methoxyquinolone, moxifloxacin: a comparison in humans and other mammalian species. , 1999, The Journal of antimicrobial chemotherapy.