Effect of Ciprofloxacin on the Plasma Concentration of Doxorubicin, Following Acute and Chronic Dose Protocol in Sprague Dawley Rats

Abstract

The objectives of the present study were to evaluate an interaction at plasma level between doxorubicin (Doxo) and ciprofloxacin (Cipro) and to determine schedule dependent (acute-chronic) effect of Doxo alone and in combination with Cipro on the plasma concentration of male adult Sprague,Dawley rats. In the chronic protocol, rats were randomized to receive intra-peritoneal (i.p.) injections of 1, or 2.5 mg kg(-1) (twice a week) of Doxo alone and in combination with Cipro (20 mg kg(-1) daily) for the duration of 3 weeks along with a placebo control. For acute schedule, rats were subjected to receive Doxo alone (6 or SS mg kg(-1)) or in combination with Cipro (20 mg kg) as a single injection and placebo treatment with saline (control). The plasma levels of Doxo were measured by using Enzyme-Linked Immuno Sorbent Assay (ELISA) technique. The plasma concentration of Doxo after the treatment with Doxo alone or in combination with Cipro (20 mg kg(-1)) significantly increased than that of control (p<0.0001). Cipro (20 mg kg) significantly increased the plasma concentration of Doxo following chronic and acute protocols (1 or 6 mg kg) by 26 and 23%, respectively. The plasma concentration of Doxo in acute (15 mg kg) and chronic (2.5 mg kg) group was significantly increased by 16.4 and 14.3%, respectively. Whereas, acute or chronic dose protocol did not show any significant differences. The increase in plasma concentration with Doxo +Cipro can be subjected to the inhibition of CYP3A4 and CYP1A2 isoenzyme by Cipro which is thought to be responsible for metabolism of Doxo. The increase in plasma concentration can lead to unforeseen toxicities. The present study also stresses on the pharmacolcinetic investigation in human and the population where the drug is to be employed clinically because of polymorphism and inter-individual variation.