EFFECT OF OFLOXACIN ON TIZANIDINE PHARMACOKINETICS IN RATS

Dipika S. Sherkar, Vaibhav G. Bhamre, Deelip V. Derle, Minal R. Narkhede, Jitesh H. Shet and Amit Tiwari

Objective of this work was to study the effect of ofloxacin on bioavailability and other pharmacokinetic parameters of tizanidine in rats. A single dose parallel design was used with 36 animals randomly divided in reference group and test group. All the rats received 7 mg tizanidine orally and in test group 200 mg ofloxacin was co-administered with tizanidine. Nine blood samples were collected from each animal over a 24-hour period. Plasma tizanidine concentrations were determined by HPTLC using UV detection, and pharmacokinetic parameters were determined by non-compartmental method. The mean value of the peak plasma concentration (Cmax) of tizanidine decreased significantly (8.47%, P value <0.001; 90% CI, 91.32% -91.72%) in animals who had given the drug with ofloxacin (Cmax , 31.54 ± 0.16 μg/mL) than those who had given the drug with water (Cmax, 34.46 ± 0.07 μg/mL). The area under the plasma concentration time curve from t=0 to time of the last measureable concentration (AUC0-t) was also increased significantly (17.17%, P value <0.001; 90% CI, 116.99% -117.34%). Similarly, the value of area under the concentration-time curve from t=0 to infinity (AUC0-∞) value was increased significantly (5.24% %, P value <0.001; 90% CI, 103.77% -104.83%); these changes were not within the 90% CI range of 80.000 - 125.000 % which is the acceptable range of bioequivalence. Tmax, T1/2, terminal elimination rate constant (λz), CL/F value, Vd/F value, AUMC0-t and AUMC0-∞ values, MRT0-t and MRT0-∞ values and % relative bioavailability (Fr) value for test group were also determined and compared with reference group. Form results the values of Cmax and AUC0-∞ were not within the bioequivalence acceptable range and from statistical analysis the reference and test samples were found to be bio-in-equivalent, suggesting the improved tizanidine oral bioavailability and therapeutic efficacy due to co-administration of ofloxacin