Pharmacokinetic/pharmacodynamic modelling in oncological drug development.
For many oncological agents, myelosuppression is the dose-limiting toxicity and the quantitative characterisation of the relationship between drug dose, plasma concentration and haematological toxicity is of importance in the drug development. Mechanism-based population pharmacokinetic-pharmacodynamic models have been developed for this purpose and the applications of these in candidate selection, first-in-man studies, prodrug and formulation development, dose finding, schedule optimisation, assessing influence of modifying agents, drug combination studies, subgroup identification and feedback individualisation are reviewed.
Karlsson
Mats O
MO
Division of Pharmacokinetics and Drug Therapy, Department of Pharmaceutical Biosciences, Faculty of Pharmacy, Uppsala University, Box 591, SE-751 24 Uppsala, Sweden. mats.karlsson@farmbio.uu.se
Anehall
Therese
T
Friberg
Lena E
LE
Henningsson
Anja
A
Kloft
Charlotte
C
Sandström
Marie
M
Xie
Rujia
R
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical; D004334:Drug Administration Schedule; D015195:Drug Design; D004359:Drug Therapy, Combination; D006801:Humans; D008954:Models, Biological; D011355:Prodrugs / Q000493:pharmacokinetics
D000970:Antineoplastic Agents; D011355:Prodrugs