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

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.