作者
Huixin Yu, Julie M Janssen, Emilia Sawicki, JG Coen van Hasselt, Vincent A de Weger, Bastiaan Nuijen, Jan HM Schellens, Jos H Beijnen, Alwin DR Huitema
发表日期
2020/3
期刊
The Journal of Clinical Pharmacology
卷号
60
期号
3
页码范围
340-350
简介
Oral administration of docetaxel is an attractive alternative for conventional intravenous (IV) administration. The low bioavailability of docetaxel, however, hinders the application of oral docetaxel in the clinic. The aim of the current study was to develop a population pharmacokinetic (PK) model for docetaxel and ritonavir based on the phase 1 studies and to support drug development of this combination treatment. PK data were collected from 191 patients who received IV docetaxel and different oral docetaxel formulations (drinking solution, ModraDoc001 capsule, and ModraDoc006 tablet) coadministered with ritonavir. A PK model was first developed for ritonavir. Subsequently, a semiphysiological PK model was developed for docetaxel, which incorporated the inhibition of docetaxel metabolism by ritonavir. The uninhibited intrinsic clearance of docetaxel was estimated based on data on IV docetaxel as 1980 L/h …
引用总数
20202021202220232321
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