Group A2 Analogs of Innovator Teicoplanin: Variability of their Ratio during Treatment Time Course in Human Blood; Consequences for the Generics

Abstract

Absence of therapeutic equivalence (TE) of generic antibiotics versus the innovator has been reported, even in case of pharmaceutical equivalence (PE).The pharmaceutically active principle of teicoplanin is mainly represented by the A2 group analogs (A2-1 to A2-2) which exist in given ratios in the innovator.We studied the evolution of these ratios in humans volunteers receiving 2 dosage regimen (6mg/kg IV every 12 hours, 3 times, and then 6 mg/kg per day for ten days -group1-, and 12 mg/kg IV every 12h, 3 times, followed by 15 mg/kg every other day till D11 -group 2-), by a specific HPLC methodology, after single dose (D1) and at steady state at day 11(D11).The less lipophilic analogs A2-1, A2-2, and A2-3 percentage decreases respectively were 18%, 11%, and 21% (group 1) and 34%, 14%, and 15% (group 2) between D1 and D11 for trough concentrations. At the same time, the more lipophilic A2-4 and A2-5 analogs ratio increases respectively were 15% and 19% (group 1) and 13% and 30% (group 2). These variations raise the problem of generics having the same global qualitative composition of analogs (PE) but with differing initial ratios. The bactericidal activity of innovator teicoplanin is optimal at its own ratios of the different analogs that act in a synergistic manner. Regarding generics, it would lead to final ratio in blood and tissues that are at risk of a sub optimal bactericidal activity. Thus, concluding in bioequivalence and therapeutic equivalence of these generics with the innovator remains highly questionable.