Effect of cyclosporine, a P-glycoprotein inhibitor, on the pharmacokinetics of cefepime in rat blood and brain: a microdialysis study.
In clinical application, cefepime and cyclosporine are regularly combined in the treatment of organ transplant patients, so the interaction of these two drugs can be hypothesized. Therefore, the pharmacokinetics of cefepime alone and in combination with cyclosporine in rat using microdialysis coupled with HPLC-UV on-line system was evaluated in the study. Cefepime at three doses (20, 50, and 100 mg/kg) showed linear kinetics. After addition of cyclosporine, the mean residence time was increased from 34.9 min to 48.6 min (p<0.05, n=6), and the area under the concentration versus time curve (AUC) increased from 4775 min microg/ml to 6960 min microg/ml (p<0.01, n=6). While in the brain, AUC increased from 64.3 min microg/ml to 110.2 min microg/ml. In summary, cyclosporine (20 mg/kg) could significantly alter the simultaneously administered cefepime (50 mg/kg) unbound drug pharmacokinetic parameters in both blood and brain.
Chang
Y L
YL
Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
Chou
M H
MH
Lin
M F
MF
Chen
C F
CF
Tsai
T H
TH
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D000818:Animals; D019540:Area Under Curve; D001921:Brain / Q000378:metabolism*; D000077723:Cefepime; D002511:Cephalosporins / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000494:pharmacology*; D004347:Drug Interactions; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002511:Cephalosporins; D007166:Immunosuppressive Agents; D000077723:Cefepime; D016572:Cyclosporine