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

• Published in: Anti-cancer drugs Vol. 12; no. 7; pp. 591 - 593
• Main Authors: Malingré, Mirte M, Ten Bokkel Huinink, Wim W, Duchin, Ken, Schellens, Jan HM, Beijnen, Jos H
• Format: Journal Article
• Language: English
• Published: England Lippincott Williams & Wilkins, Inc 01-08-2001
• Subjects: Absorption; Administration, Oral; Antineoplastic Agents, Phytogenic - administration & dosage; Area Under Curve; Biological Availability; Cyclosporine - pharmacokinetics; Drug Therapy, Combination; Enzyme Inhibitors - pharmacokinetics; Humans; Neoplasms - drug therapy; Neoplasms - metabolism; Paclitaxel - administration & dosage
• ISSN: 0959-4973; 1473-5741
• DOI: 10.1097/00001813-200108000-00005

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 in combination with a dose of oral CsA of 15 mg/kg. Dose escalation of paclitaxel from 60 to 300 mg/m 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.