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.
Malingré
M M
MM
Department of Medical Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, The Netherlands. apmmg@slz.nl
Ten Bokkel Huinink
W W
WW
Duchin
K
K
Schellens
J H
JH
Beijnen
J H
JH
D000042:Absorption; D000284:Administration, Oral; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D019540:Area Under Curve; D001682:Biological Availability; D016572:Cyclosporine / Q000493:pharmacokinetics*; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D017239:Paclitaxel / Q000008:administration & dosage*
D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D016572:Cyclosporine; D017239:Paclitaxel