title: Extrapolation of preclinical pharmacokinetic data to therapeutic drug use.
abstract: 1. Preclinical in vivo and in vitro studies are fundamental to the safe and effective development of new drugs. 2. Pharmacokinetic and metabolic research is essential to a better understanding of the pharmacological and toxicological activities of drugs and their metabolites. 3. Data generated by such a strategy can be used to improve Phase I trials, particularly those for anticancer drugs. 4. Human and animal in vitro models are potentially powerful preclinical tools in: (i) The prediction of the pharmacological behaviour of analogues belonging to the same family, e.g. vinca alkaloids; (ii) The selection of the animal species most closely related to humans on the basis of metabolic pattern; (iii) The assessment of the duration of drug action--particularly those drugs exhibiting different metabolic clearances (e.g. benzodiazepines); (iv) The understanding and prediction of drug interactions, i.e. those described for cyclosporin A and macrolide antibiotics; and (v) The explanation of the metabolic origins of interindividual variabilities in pharmacological activity.
authors.affiliation: INSERM U-278, Laboratoire Hospitalo-Universitaire de Pharmacocinétique et de Toxicocinétique, Faculté de Pharmacie, Marseille, France.
authors.forename: R
authors.initials: R
authors.lastname: Rahmani
authors.forename: B
authors.initials: B
authors.lastname: Richard
authors.forename: G
authors.initials: G
authors.lastname: Fabre
authors.forename: J P
authors.initials: JP
authors.lastname: Cano
mesh_terms: D000818:Animals; D001569:Benzodiazepines / Q000378:metabolism; D001711:Biotransformation; D004341:Drug Evaluation; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D004358:Drug Therapy; D006801:Humans; D008107:Liver Diseases / Q000378:metabolism; D008297:Male; D008942:Mitoxantrone / Q000009:adverse effects / Q000378:metabolism; D010599:Pharmacokinetics; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D014748:Vinca Alkaloids / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D014748:Vinca Alkaloids; D001569:Benzodiazepines; D008942:Mitoxantrone