Disposition of [G-(3)H]paclitaxel and cremophor EL in a patient with severely impaired renal function.

摘要: In the present work, we studied pharmacokinetics and metabolic disposition of [G-(3)H]paclitaxel in a female patient with recurrent ovarian cancer severe renal impairment (creatinine clearance: approximately 20 ml/min) due to chronic hypertension prior cisplatin treatment. During six 3-weekly courses paclitaxel at dose level 157.5 mg/m(2) (viz. 10% reduction), function remained stable. Pharmacokinetic evaluation revealed reproducible surprisingly high area under plasma concentration-time curve 26.0 +/- 1.11 microM.h (mean S.D.; n = 6; c.v. 4.29%), terminal half-life 29 h. Both parameters are substantially increased ( 1.5-fold) when compared kinetic data obtained from patients normal function. The cumulative urinary excretion parent drug was consistently low averaged 1.58 0.417% (+/- S.D.) dose. Total fecal (measured one course) 52.9% delivered radioactivity, mainly comprised known mono- dihydroxylated metabolites, unchanged accounting for only 6.18%. vehicle Cremophor EL, which can profoundly alter kinetics paclitaxel, 114.9 5.39 microl.h/ml, not different historic or mild dysfunction. Urinary EL less than 0.1% total amount administered. These indicate that substantial increase systemic exposure relates decreased metabolism and/or elimination polar radioactive species, most likely lacking an intact taxane ring fragment.