口服环孢素A与紫杉醇联合给药时的药代动力学，以增强紫杉醇的口服吸收。

Pharmacokinetics of oral cyclosporin A when co-administered to enhance the oral absorption of paclitaxel.

作者信息

Malingré M M, Ten Bokkel Huinink W W, Duchin K, Schellens J H, Beijnen J H

机构信息

Department of Medical Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, The Netherlands.

出版信息

Anticancer Drugs. 2001 Aug;12(7):591-3. doi: 10.1097/00001813-200108000-00005.

DOI:10.1097/00001813-200108000-00005

PMID:11487715

Abstract

The objective of this study was to evaluate the pharmacokinetics of oral cyclosporin A (CsA) when co-administered to enhance the oral absorption of paclitaxel. Patients received oral paclitaxel in doses of 60-360 mg/m(2) in combination with a dose of oral CsA of 15 mg/kg. Dose escalation of paclitaxel from 60 to 300 mg/m(2) resulted in a significant decrease in the area under the concentration-time curve (AUC) of CsA from 24.4+/-9.9 to 17.6+/-2.8 mg/l.h (p=0.03) (n=28). In conclusion, increases in the paclitaxel dose resulted in a decrease in the AUC of CsA. This observation may be explained by the increase in the co-solvent Cremophor EL of paclitaxel causing reduced absorption of CsA.

摘要

本研究的目的是评估口服环孢素A（CsA）与紫杉醇合用时的药代动力学，以增强紫杉醇的口服吸收。患者接受剂量为60 - 360 mg/m²的口服紫杉醇，并联合15 mg/kg的口服CsA。紫杉醇剂量从60 mg/m²增加到300 mg/m²导致CsA的浓度-时间曲线下面积（AUC）从24.4±9.9降至17.6±2.8 mg/l·h（p = 0.03）（n = 28）。总之，紫杉醇剂量增加导致CsA的AUC降低。这一观察结果可能是由于紫杉醇的助溶剂聚氧乙烯蓖麻油（Cremophor EL）增加，导致CsA吸收减少所致。