Lack of bioequivalence of two oxytetracycline formulations in the rabbit

Chong, W; Kim, Y J; Kim, S D; Han, S K; Ryu, P D

Abstract

Oxytetracycline (OTC) has been used for over 40 years in veterinary medical field. Various forms of oxytetracycline preparations have been marketed, but little information is available on the bioequivalence of OTC preparations. This study was conducted to evaluate the bioequivalence of two OTC powder preparations available in Korea. Fourteen rabbits were randomly allocated into two groups. During the first period, a dose (200 mg/kg) of reference product was orally administered to the rabbits in Group A and test product to those in Group B. After 7-day washout period the reference and test products were given in group B and A, respectively. Blood samples were drawn at 17 points during 48 hours after administration and plasma OTC concentrations were measured by using HPLC. The solution concentrations of OTC dissolved from two products were not significantly different in the dissolution test. The mean area under the curve (AUC0-∞) and peak plasma concentration (Cmax) values for test and reference OTCs were 7.22 +/- 3.90 and 11.04 +/- 7.37 microgram h/ml, 1.11 +/- 0.65 and 1.85 +/- 1.15 microgram/ml, respectively. The relative bioavailability and Cmax of test product to those of reference product was 65.4% and 60.0%, respectively. The ranges of AUC and Cmax of test drug compared to those of reference drug under 90% confidence limits were 27 104% and 28 91.5%, respectively. The results of statistical analysis indicate that the two pivotal pharmacokinetic parameters, AUC and Cmax of test product are not within the 20% of those of the reference, suggesting that the test OTC is not bioequivalent to the reference OTC.