Abstract

The pharmacokinetics and bioavailability of four major gentamicin components (C 1 , C 1a , C 2 and C 2a ) in chicken plasma administered at 5 mg/kg body weight by different routes of administration (IV, IM, SC and oral) was determined using reversed-phase high performance liquid chromatography (RP-HPLC) and pre-column derivatization with Phenylisocyanate (PIC). All the components, except for C 1a were well absorbed (bioavailability of 60% or greater) following administration by the IM and SC routes. The bioavailability of C 1a was 58% and 35% following IM and SC administration, respectively. The apparent volume of distribution (V ss and Vd area ) for the C 1 component was significantly smaller than for any of the other components individually or combined. In addition, the C 1 component had a significantly shorter t½β and MRT following intravenous administration and a higher C max /Dose following intramuscular administration. This study showed significant differences in some pharmacokinetics parameters between four gentamicin components (C 1a , C 2a , C 1 and C 2 ) after administration of single mixture of gentamicin by different routes in chickens. The differences may have clinical and toxicological implications, and could explain the high variation in total gentamicin pharmacokinetics.

Highlights

  • The pharmacokinetics and bioavailability of four major gentamicin components (C1, C1a, C2 and C2a) in chicken plasma administered at 5 mg/kg body weight by different routes of administration (IV, IM, SC and oral) was determined using reversed-phase high performance liquid chromatography (RP-HPLC) and pre-column derivatization with Phenylisocyanate (PIC)

  • European Pharmacopoeia [7] determines the amount of C1, C1a and the sum of C2 and C2a were limited to 20-35, 10-30 and 40-60%, respectively

  • A representative HPLC chromatogram of blank chicken plasma containing PIC and TEA without gentamicin and the separation of the gentamicin components in chicken plasma are illustrated in figures 1A and 1B, respectively

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Summary

Introduction

The pharmacokinetics and bioavailability of four major gentamicin components (C1, C1a, C2 and C2a) in chicken plasma administered at 5 mg/kg body weight by different routes of administration (IV, IM, SC and oral) was determined using reversed-phase high performance liquid chromatography (RP-HPLC) and pre-column derivatization with Phenylisocyanate (PIC). Gentamicin is a broad-spectrum bactericidal aminoglycoside antibiotic, produced by fermentation of Micromonospora purpura or M. echinospora. It is effective against wide variety of serious bacterial infections caused by susceptible gram-negative and some grampositive aerobic bacteria [1,2]. Gentamicin has no UV or visible absorbing chromophores and cannot be detected by traditional techniques without derivatisation [11,12]. Gentamicin has been derivatised previously with O-phthalaldehyde (OPA), dansyl chloride, fluorescamine, 9-fluorenylmethyl chloroformate (FMOC-CI), 1-fluoro-2, 4-dinitrobenzene (DNFB) and 2,4,6-trinotrobenzenesulfonic acid (TNBS) [11]

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