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Pharmacologic study of Cremophor EL in cancer patients with impaired hepatic function receiving paclitaxel

Department of Medical Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands, Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam, The Netherlands

Manon T Huizing, MD, PhD

Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam, The Netherlands

Olaf van Tellingen, PhD

Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam, The Netherlands

Robert A Hakvoort, MD

Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam, The Netherlands

Pax H B Willemse, MD, PhD

Department of Medical Oncology, Academic Hospital Groningen, Groningen, The Netherlands

Alexander De Graeff, MD, PhD

Department of Medical Oncology, Academic Hospital Utrecht, Utrecht, The Netherlands

Jan B Vermorken, MD, PhD

Department of Medical Oncology, University Hospital Antwerpen, Edegem, Belgium

Jos H Beijnen, PhD

Department of Medical Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands, 2Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute/Slotervaart Hospital, Amsterdam, The Netherlands, Department of Pharmaceutical Analysis and Toxicology, Faculty of Pharmacy, State University of Utrecht, Utrecht, The Netherlands

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.

Key Words: Cremophor EL • liver function • pharmacokinetics • paclitaxel

Journal of Oncology Pharmacy Practice, Vol. 5, No. 2, 83-86 (1999)
DOI: 10.1177/107815529900500204


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