Bioanalysis, pharmacokinetics, and pharmacodynamics of the novel anticancer drug paclitaxel (Taxol).
Several high-performance liquid chromatographic assays have been reported for the analysis of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in biologic matrices. The recently developed method of using solid-phase extraction as a sample pretreatment is preferred, as it is the most sensitive assay and is also capable of detecting metabolites in the plasma of treated patients. The pharmacokinetics of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), administered in different doses and schedules, has been studied using this method. After cessation of the infusion, a three-phasic decay of plasma concentrations has been found. There are indications for nonlinear pharmacokinetics when paclitaxel is administered as a short infusion and at higher doses. Different metabolic products of paclitaxel have been detected in the plasma of treated patients. Three hydroxylated metabolites have been identified so far. Pharmacokinetics have been related with pharmacodynamics. Neuropathy, mucositis, and leukopenia correlate with pharmacokinetic parameters such as area under the plasma concentration time curve and steady-state paclitaxel levels. The hematologic toxicity of paclitaxel also has been modelled with a sigmoidal maximum effect equation with the time spent above the biologically active threshold concentration of 0.1 mumol/L as a pharmacokinetic parameters.
Beijnen
J H
JH
European Cancer Centre, Amsterdam, The Netherlands.
Huizing
M T
MT
ten Bokkel Huinink
W W
WW
Veenhof
C H
CH
Vermorken
J B
JB
Giaccone
G
G
Pinedo
H M
HM
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D006801:Humans; D008099:Liver / Q000378:metabolism; D051379:Mice; D017239:Paclitaxel / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D013997:Time Factors
D017239:Paclitaxel