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Bitespiramycin is a macrolide antibiotic consisting of a mixture of some nine spiramycin ester derivatives. It has a similar spectrum of antibiotic activity to that of spiramycin but has superior pharmacokinetic properties. In this study, a rapid and facile LC/ESI-MSn method was applied to study the metabolism of bitespiramycin in rat following a single oral dose (80 mg kg-1). Concentrations of parent drug constituents and metabolites were determined in plasma, urine, feces and bile. Concentrations of parent drug constituents and metabolites in plasma were very low. In urine, feces and bile, parent drug constituents and 38 metabolites were identified on the basis of their chromatographic and mass spectrometric properties. The identity of 17 metabolites was confirmed by comparison with reference substances. The principal metabolites were the corresponding spiramycins formed by hydrolysis of the 4''-(3-methylbutanoate) groups. Other important metabolic pathways were: hydrolytic loss of the forosamine and mycarose sugars; aldehyde reduction; cysteine conjugation of the aldehyde group; and hydrolysis of the lactone ring. Products formed by lactone ring opening were found only in urine, and those formed by aldehyde reduction were found only in feces. Aldehyde reduction and hydrolytic loss of forosamine represent novel biotransformation pathways for spiramycin derivatives.

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