Oral bioavailability of a novel paclitaxel formulation (Genetaxyl) administered with cyclosporin A in cancer patients

Zyting Chu, Jen Shi Chen, Chi Ting Liau, Hung Ming Wang, Yung Chang Lin, Muh Hwa Yang, Po Min Chen, Erin R. Gardner, William D. Figg, Alex Sparreboom*

*此作品的通信作者

研究成果: Article同行評審

30 引文 斯高帕斯(Scopus)

摘要

The formulation excipient Cremophor EL (CrEL) is known to limit the absorption of oral paclitaxel given together with cyclosporin A. We hypothesized that the use of oral Genetaxyl, a paclitaxel formulation containing only 20% CrEL would have an improved oral bioavailability. Cohorts of six patients were treated with oral Genetaxyl at a dose of 60, 120, or 180 mg/m 2 and 10 mg/kg of oral cyclosporin A in cycle 1. In cycle 2, patients received intravenous (i.v.) Genetaxyl (175 mg/m 2, 3-h infusion). Three additional patients received one dose of generic i.v. paclitaxel (Genaxol, containing 50% CrEL; 175 mg/m 2, 3-h infusion). The median area under the plasma concentration-time curve (AUC) and peak concentration of total paclitaxel following i.v. Genetaxyl were lower than those for i.v. Genaxol, as a result of significantly increased clearance (P=0.017), and the AUC ratio for unbound to total paclitaxel for i.v. Genetaxyl was about two times higher than that for i.v. Genaxol (P=0.0077). After oral administration of Genetaxyl at doses of 60, 120, and 180 mg/m 2, the median total paclitaxel AUCs were 1.29, 1.60, and 1.85(μg ×h/ml, respectively, suggesting a less than proportional increase in systemic exposure with increasing doses. The corresponding median values for the apparent bioavailability of oral Genetaxyl were similar when compared with i.v. Genetaxyl, when calculated either on the basis of data for total paclitaxel (30.1%) or unbound paclitaxel (30.6%).

原文English
頁(從 - 到)275-281
頁數7
期刊Anti-Cancer Drugs
19
發行號3
DOIs
出版狀態Published - 3月 2008

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