Pharmacokinetic drug–drug interaction study between clindamycin and cyclosporin in rabbits

Abstract
Cyclosporine A (CSA) is an immunosuppressant drug, metabolized mainly by CYP3A4 that is one of the CytochromeP450 enzymes. Clindamycin (CLN) is a lincosamide antibiotic, inducing CYP3A4 activity in vitro, and thereby mayalter CSA pharmacokinetics (PK). The current research was performed to investigate the PK parameters changes ofCSA up on co-administrating with CLN in healthy male rabbits. Twelve healthy male rabbits randomly were selectedand divided into two groups: Control set (n = 6) in which the rabbits were received oral normal saline CSA solution(10 mg/kg/day), meanwhile rabbits in the test group (n = 6) were treated with oral normal saline CSA solution (10 mg/kg/day) concomitantly with normal saline solution of CLN (8 mg/kg/day) at the same time for 7 days. Blood samples(2 ml) were collected and CSA concentrations were measured in whole blood at the predetermined time points byusing Chemiluminescent Immunoassay (CLIA) detection kit. PK profiles of CSA for both groups in the control andtest groups including Cmax, tmax, AUC0-24, the area under the blood concentration–time curve from 0 hour to infinity(AUC0-∞), t½, and Ke were compared. The results showed a statistically insignificant differences in the PK parametersof CSA alone or combined with CLN with p > 0.05. In conclusion, it has been found that CLN does not affect the CSAPK. Further confirmation of our findings is requiered in humans before these results can be applied in patient care.
Description
Keywords
Cyclosporine, clindamycin, drug interaction, pharmacokinetic, CYP3A4.
Citation
Issam Mohammed Abushammala, Lama Attef El Gussein, Badea Elzaman Zomlot, Kamal Fakher Abushammalleh, Mohammed Mahmoud Taha, Mohammed Yousef Miqdad. Pharmacokinetic drug–drug interaction study between clindamycin and cyclosporin in rabbits. Journal of Applied Pharmaceutical Science. 2020 Feb; 2020 Feb: 108-111