Perspectives on the history and scientific contributions of Gerhard Levy

Gerhard Levy (Fig. 1) was born February 12, 1928 in Wollin, Germany, and obtained his early education in China. An oral history of his childhood experiences in Nazi Germany and China is available online (http://collections. ushmm.org/search/catalog/irn511804). Gary attended the University of California at San Francisco earning the BS in Pharmacy in 1955 and PharmD in 1958. Nearly his entire career was spent at the University of Buffalo (UB) having joined as Assistant Professor of Pharmacy in 1958 and retiring as University Distinguished Professor of Pharmaceutics in 2000. His own personal perspectives on his career and the development of pharmacodynamics as a pharmaceutical science were published in the Annals of Pharmacotherapy in 2006 [1]. Gary accumulated a lengthy list of national and international professional awards including the Høst Madsen Medal from the International Pharmaceutical Federation (FIP) in 1978, the Oscar Hunter Award in Experimental Therapeutics in 1982 from the American Society for Pharmacology and Experimental Therapeutics, the Volwiler Award in 1982 from the American Association of Colleges of Pharmacy, the Takeru Higuchi Research Prize in 1983 from the American Pharmaceutical Association, the Lifetime Achievement Award in Pharmaceutical Sciences in 1994 from the FIP, plus 20 honorary lectureships at various universities and venues and 6 Doctor Honoris Causae Awards. He fondly describes the impressive ceremony with a massive cannon discharge when his honorary doctorate was bestowed in Uppsala, Sweden in 1975. We have his cannon shell, top hat, and certificate on display in our building. His proceeds from the Higuchi Prize were deposited into a university account and have funded the Buffalo Pharmaceutics Scholar Award, which to date has recognized 32 outstanding students in the Buffalo PhD program. Their names and photographs are displayed in our primary graduate classroom, The Gerhard Levy Seminar Room (Kapoor 443). Gary was also the first pharmacist named to the prestigious Institute of Medicine, National Academy of Sciences, in 1980. We host the annual Gerhard Levy Distinguished Lectureship each fall, with several of the recipients contributing their comments in this article.

[1]  G. Levy,et al.  Kinetics of the anticoagulant effect of bishydroxycoumarin in man , 1970, Clinical pharmacology and therapeutics.

[2]  A. Yacobi,et al.  Comparative pharmacokinetics of coumarin anticoagulants XXIX: Elimination kinetics and anticoagulant activity of (S)-(-)-warfarin in rats before and after chronic administration. , 1977, Journal of pharmaceutical sciences.

[3]  G Levy,et al.  Kinetics of drug action in disease states. XIV. Effect of infusion rate on pentylenetetrazol concentrations in serum, brain and cerebrospinal fluid of rats at onset of convulsions. , 1985, The Journal of pharmacology and experimental therapeutics.

[4]  G. Levy,et al.  Comparative pharmacokinetics of salicylate elimination in man and rats. , 1966, The Journal of pharmacology and experimental therapeutics.

[5]  G. Levy,et al.  Letter: Determination of salicylate and its metabolites in urine. , 1976, Clinical chemistry.

[6]  W. Jusko,et al.  EFFECT OF VISCOSITY ON DRUG ABSORPTION. , 1965, Journal of pharmaceutical sciences.

[7]  C. Regårdh,et al.  Drug biotransformation interactions in man. V. Acetaminophen and salicylic acid. , 1971, Journal of pharmaceutical sciences.

[8]  G Levy,et al.  Pharmacokinetic evidence for saturable renal tubular reabsorption of riboflavin. , 1970, Journal of pharmaceutical sciences.

[9]  L. Whitfield,et al.  Relationship between concentration and anticoagulant effect of heparin in plasma of normal subjects: Magnitude and predictability of interindividual differences * , 1980, Clinical pharmacology and therapy.

[10]  G. Levy,et al.  Effect of folic acid on the pharmacokinetics of acutely administered phenytoin in pregnant and nonpregnant rats. , 1984, Journal of pharmaceutical sciences.

[11]  D. Greenblatt,et al.  Pharmacokinetics in clinical practice , 1985 .

[12]  G. Levy,et al.  Physicochemical basis of the buffered acetylsalicylic acid controversy. , 1960, The New England journal of medicine.

[13]  Kelly Fellows,et al.  Bayesian population modeling of drug dosing adherence , 2015, Journal of Pharmacokinetics and Pharmacodynamics.

[14]  W. Jusko,et al.  Effect of age on intestinal absorption of riboflavin in humans. , 1970, Journal of pharmaceutical sciences.

[15]  G. Levy,et al.  Drug biotransformation interactions in man VI: acetaminophen and ascorbic acid. , 1971, Journal of pharmaceutical sciences.

[16]  G Levy,et al.  Comparative pharmacokinetics of coumarin anticoagulants. XLIX: Nonlinear tissue distribution of S-warfarin in rats. , 1989, Journal of pharmaceutical sciences.

[17]  M. Danhof Kinetics of drug action in disease states: towards physiology-based pharmacodynamic (PBPD) models , 2015, Journal of Pharmacokinetics and Pharmacodynamics.

[18]  G Levy,et al.  Renal clearance and serum protein binding of acetaminophen and its major conjugates in humans. , 1984, Journal of pharmaceutical sciences.

[19]  W. Jusko,et al.  Factors affecting the absorption of riboflavin in man. , 1966, Journal of pharmaceutical sciences.

[20]  W. Hayton,et al.  Effect of complex formation on drug absorption. XII. Enhancement of intestinal absorption of prednisone and prednisolone by dialkylpropionamides in rats. , 1972, Journal of pharmaceutical sciences.

[21]  G Levy,et al.  Predicting Effective Drug Concentrations for Individual Patients , 1998, Clinical pharmacokinetics.

[22]  G. Levy,et al.  Relationship between effect of activated charcoal on drug absorption in man and its drug adsorption characteristics in vitro. , 1972, Journal of pharmaceutical sciences.

[23]  D. Perrier,et al.  Effect of product inhibition on kinetics of drug elimination , 1973, Journal of Pharmacokinetics and Biopharmaceutics.

[24]  G Levy,et al.  Multicompartment pharmacokinetic models and pharmacologic effects. , 1969, Journal of pharmaceutical sciences.

[25]  L. Hollister,et al.  Variation in Rate of Salicylate Elimination by Humans , 1964, British medical journal.

[26]  G. Levy EFFECT OF PROTEIN BINDING ON THE PHARMACOLOGIC ACTIVITY OF DRUGS AS EXEMPLIFIED BY WARFARIN , 2009 .

[27]  Torsten Teorell,et al.  Kinetics of distribution of substances administered to the body, II : The intravascular modes of administration , 1937 .

[28]  D. Shah Pharmacokinetic and pharmacodynamic considerations for the next generation protein therapeutics , 2015, Journal of Pharmacokinetics and Pharmacodynamics.

[29]  G. Levy,et al.  Kinetics of pharmacologic effects in man: The anticoagulant action of warfarin , 1969, Clinical pharmacology and therapeutics.

[30]  G. Levy,et al.  Pharmacokinetics of succinylcholine in newborns. , 1970, Anesthesiology.

[31]  G. Levy,et al.  Inhibition of drug metabolism by hydroxylated metabolites: cross-inhibition and specificity. , 1975, Journal of pharmaceutical sciences.

[32]  Richard P. Lewis,et al.  Pharmacokinetics of digoxin: Relationship between response intensity and predicted compartmental drug levels in man , 1979, Journal of Pharmacokinetics and Biopharmaceutics.

[33]  M. Wientjes,et al.  Nonlinear pharmacokinetics of aspirin in rats. , 1988, The Journal of pharmacology and experimental therapeutics.

[34]  C. Regårdh Pharmacokinetics and biopharmaceutics of some adrenergic beta-receptor antagonists with special emphasis on alprenolol and metoprolol. , 2009, Acta pharmacologica et toxicologica.

[35]  G Levy,et al.  Case history of a pharmaceutical formulation failure , 1967, Clinical pharmacology and therapeutics.

[36]  G. Levy Comparison of dissolution and absorption rates of different commercial aspirin tablets. , 1961, Journal of pharmaceutical sciences.

[37]  J. Slattery,et al.  Acetaminophen kinetics in acutely poisoned patients , 1979, Clinical pharmacology and therapeutics.

[38]  F. H. Dost,et al.  Der Blutspiegel : Kinetik der Konzentrationsabläufe in der Kreislaufflüssigkeit , 1953 .

[39]  M. Gibaldi,et al.  Pharmacokinetics in clinical practice. I. Concepts. , 1976, JAMA.

[40]  G Levy,et al.  Kinetics of drug action in disease states. XXV. Effect of experimental hypovolemia on the pharmacodynamics and pharmacokinetics of desmethyldiazepam. , 1988, The Journal of pharmacology and experimental therapeutics.

[41]  G. Levy,et al.  RELATIONSHIP BETWEEN ELIMINATION RATE OF DRUGS AND RATE OF DECLINE OF THEIR PHARMACOLOGIC EFFECTS. , 1964, Journal of pharmaceutical sciences.

[42]  K. Giacomini,et al.  Pharmacokinetic studies of propoxyphene I:Effect of portacaval shunt on systemic availability in dogs. , 1980, Journal of pharmaceutical sciences.

[43]  G. Levy,et al.  Effect of ethanol on theophylline absorption in humans. , 1975, Journal of pharmaceutical sciences.

[44]  G. Levy,et al.  Kinetics of drug action in disease states. 45. Effect of elevated plasma creatinine concentrations on the hypnotic action of phenobarbital in normal rats. , 1994, Journal of pharmaceutical sciences.

[45]  G Levy,et al.  Kinetics of drug action in disease states. I. Effect of infusion rate on phenobarbital concentrations in serum, brain and cerebrospinal fluid of normal rats at onset of loss of righting reflex. , 1984, The Journal of pharmacology and experimental therapeutics.

[46]  G. Levy,et al.  The Study of Salicylate Pharmacokinetics in Intoxicated Infants and Children , 1968 .

[47]  Brian K. Shoichet,et al.  Prediction and validation of enzyme and transporter off-targets for metformin , 2015, Journal of Pharmacokinetics and Pharmacodynamics.

[48]  W. Jusko,et al.  Developing compliance instructions for drug labeling , 2000, Clinical pharmacology and therapeutics.

[49]  L B Sheiner,et al.  Simultaneous modeling of pharmacokinetics and pharmacodynamics: application to d-tubocurarine. , 1980, Clinical pharmacology and therapeutics.

[50]  W. Jusko,et al.  Mechanism-based mathematical modeling of combined gemcitabine and birinapant in pancreatic cancer cells , 2015, Journal of Pharmacokinetics and Pharmacodynamics.

[51]  G. Levy,et al.  Effect of heparin or salicylate infusion on serum protein binding and on concentrations of phenytoin in serum, brain and cerebrospinal fluid of rats. , 1981, The Journal of pharmacology and experimental therapeutics.

[52]  G. Levy,et al.  The role of dosage form in aspirin‐induced gastrointestinal bleeding , 1967, Clinical pharmacology and therapeutics.

[53]  G. Levy,et al.  Limited capacity for salicyl phenolic glucuronide formation and its effect on the kinetics of salicylate elimination in man , 1972, Clinical pharmacology and therapeutics.

[54]  M. Morris,et al.  Semi-mechanistic kidney model incorporating physiologically-relevant fluid reabsorption and transporter-mediated renal reabsorption: pharmacokinetics of γ-hydroxybutyric acid and l-lactate in rats , 2015, Journal of Pharmacokinetics and Pharmacodynamics.

[55]  G. Levy,et al.  Salicylate accumulation kinetics in man. , 1972, New England Journal of Medicine.

[56]  W. Krzyzanski Pharmacodynamic models of age-structured cell populations , 2015, Journal of Pharmacokinetics and Pharmacodynamics.

[57]  Jerome J. Schentag,et al.  Relationship between concentration and anticoagulant effect of heparin in plasma of hospitalized patients: Magnitude and predictability of interindividual differences * , 1980, Clinical pharmacology and therapeutics.

[58]  R E Notari,et al.  Role of pharmacokinetics in drug dosage adjustment. I. Pharmacologic effect kinetics and apparent volume of distribution of digoxin. , 1973, The Journal of clinical pharmacology and new drugs.

[59]  Lloyd Ms,et al.  Relationship between concentration and anticoagulant effect of heparin in plasma of normal subjects: Magnitude and predictability of interindividual differences * , 1980, Clinical pharmacology and therapeutics.

[60]  G LEVY,et al.  A method for the measurement of lubricating property of medicinal products. , 1957, Journal of the American Pharmaceutical Association. American Pharmaceutical Association.

[61]  L. Paalzow,et al.  Serum and brain concentrations of pentazocine in relation to analgesic activity in mice , 1972, The Journal of pharmacy and pharmacology.

[62]  Biopharmaceutical aspects of aspirin-induced gastrointestinal blood loss in man. , 1969, Journal of pharmaceutical sciences.

[63]  Vlad Ichim,et al.  MALCOLM GLADWELL, OUTLIERS. THE STORY OF SUCCESS , LITTLE, BROWN AND COMPANY, NEW YORK, 2008. , 2015 .

[64]  G. Levy,et al.  Pharmacokinetics of theophylline in children with asthma. , 1976, Pediatrics.

[65]  Scale-up of a physiologically-based pharmacokinetic model to predict the disposition of monoclonal antibodies in monkeys , 2015, Journal of Pharmacokinetics and Pharmacodynamics.

[66]  G. Levy,et al.  Pharmacokinetics of acetaminophen in the human neonate: formation of acetaminophen glucuronide and sulfate in relation to plasma bilirubin concentration and D-glucaric acid excretion. , 1975, Pediatrics.

[67]  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.

[68]  G. Levy The Pharm.D.: All or Some? , 1991, DICP : the annals of pharmacotherapy.

[69]  L. Hollister,et al.  FAILURE OF U.S.P. DISINTEGRATION TEST TO ASSESS PHYSIOLOGIC AVAILABILITY OF ENTERIC COATED TABLETS. , 1964, New York state journal of medicine.

[70]  G. Levy,et al.  Pharmaceutical formulation and therapeutic efficacy. , 1961, JAMA.

[71]  G Levy,et al.  Pharmacologic target‐mediated drug disposition , 1994, Clinical pharmacology and therapeutics.

[72]  W. Jusko,et al.  Comparative pharmacokinetics of coumarin anticoagulants L: Physiologic modeling of S-warfarin in rats and pharmacologic target-mediated warfarin disposition in man. , 2003, Journal of pharmaceutical sciences.

[73]  G Levy,et al.  Kinetics of pharmacologic effects , 1966, Clinical pharmacology and therapeutics.

[74]  W. Hayton,et al.  Effect of complex formation on drug absorption. XI. Complexation of prednisone and prednisolone with dialkylpropionamides and its effect on prednisone transfer through an artificial lipoid barrier. , 1972, Journal of pharmaceutical sciences.

[75]  G. Levy Using Other People's Data in Publications , 1998 .

[76]  G Levy,et al.  Effect of plasma protein binding on renal clearance of drugs. , 1980, Journal of pharmaceutical sciences.

[77]  D. Mager,et al.  Physiologically-based pharmacokinetic modeling of target-mediated drug disposition of bortezomib in mice , 2015, Journal of Pharmacokinetics and Pharmacodynamics.

[78]  G. Levy,et al.  Comparative pharmacokinetics of coumarin anticoagulants XXXVII: Simultaneous in vivo displacement of dicumarol from serum protein and tissue binding sites by tolbutamide in rats. , 1978, Journal of pharmaceutical sciences.

[79]  J. Wagner,et al.  Kinetics of pharmacologic response. I. Proposed relationships between response and drug concentration in the intact animal and man. , 1968, Journal of theoretical biology.

[80]  J. Lin,et al.  Pharmacokinetic consequences and toxicologic implications of endogenous cosubstrate depletion. , 1982, Drug metabolism reviews.

[81]  G. Levy,et al.  Effect of complex formation on drug absorption. IV. Role of intragastric diffusion in the absorption of free and caffeine-complexed salicylic acid from the rat stomach. , 1967, Journal of pharmaceutical sciences.

[82]  C. DeVane Parents and Mentors May Be Gone but They Are Never Forgotten , 2015, Pharmacotherapy.

[83]  G. Levy ASPIRIN: ABSORPTION RATE and ANALGESIC EFFECT , 1965, Anesthesia and analgesia.

[84]  G. Levy,et al.  Interindividual differences in the effect of drugs on bilirubin plasma binding in newborn infants and in adults , 1977, Clinical pharmacology and therapeutics.

[85]  G. Levy,et al.  Comparative pharmacokinetics of coumarin anticoagulants. I. Unusual interaction of bishydroxycoumarin with plasma proteins--development of a new assay. , 1968, Journal of pharmaceutical sciences.

[86]  J. Wagner Biopharmaceutics: absorption aspects. , 1961, Journal of pharmaceutical sciences.

[87]  G. Levy,et al.  Drug absorption and exsorption kinetics in goldfish. , 1965, Journal of pharmaceutical sciences.

[88]  G. Levy,et al.  Drug biotransformation interactions in man. II. A pharmacokinetic study of the simultaneous conjugation of benzoic and salicylic acids with glycine. , 1969, Journal of pharmaceutical sciences.

[89]  M. Gibaldi,et al.  Pharmacokinetics in clinical practice. 2. Applications. , 1976, JAMA.