Context: Teicoplanin is a fermentative antibiotic consisting of several active components that contribute similarly to the antibacterial activity, but exhibit different pharmacokinetic properties. Differences in systemic exposure between batches of teicoplanin are possible within pharmacopeial specifications as the proportion of subcomponents may vary from batch to batch.
Objective: The aim of this paper is to study the possible modification of the present pharmacopeial specification for teicoplanin composition to ensure an a priori pharmacokinetic equivalence between all pharmacopoeial-compliant batches.
Methods: The expectable whole Area Under the Curve (AUC) of plasma levels of teicoplanin was predicted for different experimental batches and also for the theoretical extreme batches within pharmacopeial specifications. Calculations were done based on the AUC of each teicoplanin active subcomponent. Subsequently, the equivalence between a generic teicoplanin and a reference drug product was investigated by means of the ratio of AUCs.
Results: Batches under study, complying with current pharmacopoeial specifications, showed a maximum predicted difference in AUC slightly larger than 40%. The observed variability in teicoplanin compositions surpasses the conventional ±5% specification used for drugs obtained by chemical synthesis, but no 5% differences have been observed for any of the AUC means of the reference product when compared with the whole pooled data.
Discussion and conclusion: Alternative specifications of actives composition can be defined to ensure that all batches complying with the pharmacopoeia are inside ±10% interval between them.
Keywords: Analytical specification; antibiotics; pharmacopoeia; relative bioavailability; teicoplanin.