Extrapolation of preclinical pharmacokinetic data to therapeutic drug use.
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.
Rahmani
R
R
INSERM U-278, Laboratoire Hospitalo-Universitaire de Pharmacocinétique et de Toxicocinétique, Faculté de Pharmacie, Marseille, France.
Richard
B
B
Fabre
G
G
Cano
J P
JP
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
D014748:Vinca Alkaloids; D001569:Benzodiazepines; D008942:Mitoxantrone