@article {Gelderblom1300, author = {Hans Gelderblom and Jaap Verweij and Eric Brouwer and Marrimuthoo Pillay and Peter de Bruijn and Kees Nooter and Gerrit Stoter and Alex Sparreboom}, title = {Disposition of [G-3H]paclitaxel and Cremophor EL in a Patient with Severely Impaired Renal Function}, volume = {27}, number = {11}, pages = {1300--1305}, year = {1999}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {In the present work, we studied the pharmacokinetics and metabolic disposition of [G-3H]paclitaxel in a female patient with recurrent ovarian cancer and severe renal impairment (creatinine clearance: \~{}20 ml/min) due to chronic hypertension and prior cisplatin treatment. During six 3-weekly courses of paclitaxel at a dose level of 157.5 mg/m2 (viz. a 10\% dose reduction), the renal function remained stable. Pharmacokinetic evaluation revealed a reproducible and surprisingly high paclitaxel area under the plasma concentration-time curve of 26.0 {\textpm} 1.11 μM.h (mean {\textpm} S.D.; n = 6; c.v. = 4.29\%), and a terminal disposition half-life of \~{}29 h. Both parameters are substantially increased (\~{}1.5-fold) when compared with kinetic data obtained from patients with normal renal function. The cumulative urinary excretion of the parent drug was consistently low and averaged 1.58 {\textpm} 0.417\% ({\textpm} S.D.) of the dose. Total fecal excretion (measured in one course) was 52.9\% of the delivered radioactivity, and mainly comprised known mono- and dihydroxylated metabolites, with unchanged paclitaxel accounting for only 6.18\%. The plasma area under the plasma concentration-time curve of the paclitaxel vehicle Cremophor EL, which can profoundly alter the kinetics of paclitaxel, was 114.9 {\textpm} 5.39 μl.h/ml, and not different from historic data in patients with normal or mild renal dysfunction. Urinary excretion of Cremophor EL was less than 0.1\% of the total amount administered. These data indicate that the substantial increase in systemic exposure of the patient to paclitaxel relates to decreased renal metabolism and/or urinary elimination of polar radioactive species, most likely lacking an intact taxane ring fragment. The American Society for Pharmacology and Experimental Therapeutics}, issn = {0090-9556}, URL = {https://dmd.aspetjournals.org/content/27/11/1300}, eprint = {https://dmd.aspetjournals.org/content/27/11/1300.full.pdf}, journal = {Drug Metabolism and Disposition} }