Aims. Cremophor EL (CrEL) (polyoxyethylene glycerol triricinoleate 35) is used as a pharmaceutical vehicle for the formulation of several drugs, including the anticancer agent paclitaxel (Taxolt). This excipient has been associated with hypersensitivity reactions and affects the pharmacokinetic properties of paclitaxel, especially in patients with hepatic dysfunction. In this study, we investigated the pharmacokinetics of CrEL in a specific population of patients.
Methods. Patients were stratified in five cohorts based on hepatic function, received paclitaxel for metastatic disease, and were monitored pharmacokinetically during course 1 and course 2. CrEL levels were measured and related to the extent of hepatic dysfunction.
Results. A total of 46 courses were measured from 27 patients. CrEL pharmacokinetic parameters in patients with mild hepatic dysfunction (cohorts I-III) were not significantly different from patients with normal hepatic function, whereas the patients with moderate to severe hepatic dysfunction (cohorts IV and V) displayed a different pharmacokinetic profile.
Conclusions. The results indicate a nonlinear pharmacokinetic behavior of CrEL. No differences were found for CrEL pharmacokinetics when course 1 was compared with course 2 per cohort. A possible influence of the specific characteristics of patients with severe hepatic dysfunction, such as altered physiologic and metabolic states, could play a role in the deposition of CrEL.
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