Assessment of Key Pharmacokinetic Variables of Bioequivalent and Non-bioequivalent Enrofloxacin Preparations under Various Water Management Conditions

Considering that a study of bioequivalence is not compulsory for drug registration in many Latin-American countries, a trial using a bioequivalent preparation of enrofloxacin (bENR) and a non-bioequivalent one (nbENR) was carried out in broilers to assess the maximum serum concentrations (Cmax) and area under the plasma drug-concentration vs. time profiles (AUC) obtained. Three levels of drug handling when delivering the medicated water to the birds have been identified in poultry producing units in Mexico i.e., poor, medium and high. The trial was carried out in eight thousand, divided in six groups with three replicates per group. Variables included in handing the medicated water were grouped to integrate the poor, medium and high groups. The highest AUC and Cmax values were obtained with the bENR handled under high standards (P<0.05). The nbENR, similarly handled, failed to achieve adequate values in these variables. Medium and poor drug management either with bENR or nbENR resulted in low to very low Cmax and AUC values, reaching a lowest value of Cmax of 0.17μg/mL, equivalent to 7% of the best Cmax (2.43μg/mL). It is concluded that excepting in the bENR handled with high standards, all groups showed insufficient Cmax/MIC and AUC/MIC ratios. Relevance of these findings for clinical efficacy and for the emergence of bacterial resistant strains is discussed.