High-performance liquid chromatographic assay for taxol in human plasma and urine and pharmacokinetics in a phase I trial.
Taxol is a unique antineoplastic agent which appears to exert its cytotoxic action as a result of interference with microtubular structure and function. Clinical development of this drug will be facilitated by the availability of sensitive and specific methods for its quantitation in biological fluids. We have developed a reverse-phase high-performance liquid chromatographic assay for taxol capable of detecting concentrations as low as 50 nM, which can be automated using readily available equipment. With this assay we have performed pharmacologic studies of taxol during the conduct of a phase I trial of this compound at The Johns Hopkins Oncology Center. Following a 60- to 360-minute infusion, the plasma disappearance is biexponential, with harmonic mean alpha half-life and beta half-life values of 16.2 minutes and 6.4 hours, respectively. Volumes of distribution for the theoretical central compartment (VDc) and at steady state (VDss) were 8.6 and 67.1 L/m2. Mean plasma clearance was 253 ml/minute/m2. Urinary clearance was 29.3 ml/minute/m2 and 5.9% +/- 8.8% of the drug was identified in 48-hour urine collections. No metabolites have been identified. Over the 18-fold dose range studied, there was no evidence of nonlinearity or dose-dependent behavior. A rough correlation between area under the plasma disappearance curve and hematologic toxicity was observed.
D000470:Alkaloids / Q000009:adverse effects / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004341:Drug Evaluation; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008657:Metabolic Clearance Rate; D009369:Neoplasms / Q000378:metabolism; D017239:Paclitaxel; D011786:Quality Control; D012984:Software
D000470:Alkaloids; D017239:Paclitaxel