Ototoxicity of a new glycopeptide, norvancomycin with multiple intravenous administrations in guinea pigs.

Time courses of plasma concentration of a new glycopeptide, norvancomycin (NVCM) after single intravenous (iv) and intraperitoneal (ip) injection, and the peak plasma concentrations (Cmax's) of this drug at various doses after single iv injection were determined in guinea pigs. There were significant differences in pharmacokinetic parameters between the two routes of administration and the Cmax linearly increased with the dose used increasing. Guinea pigs with normal hearing were then used to investigate ototoxic liability of NVCM after multiple intravenous administrations (54, 108, 216mg/kg, qd for 14 days). Postrotatory vestibular nystagmus (PRN), auditory brainstem response (ABR) and electron microscopy (SEM TEM) results showed that, similarly to vancomycin, there was no functional or morphological evidence of ototoxicity of NVCM at the dose of 54, 108 mg/kg. In the high dose group (216 mg/kg), there was a 0 approximately 4 dB elevation of hearing threshold but no morphological changes. The results suggested that the ototoxicity of NVCM is absent or minimal after multiple iv administrations within this dose range.