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Article Title

Absorption and disposition kinetics of trimethoprim following intramuscular injection in rabbits

Abstract

The absorption and disposition kinetics of an antimicrobial agent, trimethoprim (TMP) were investigated using New Zealand white male rabbits. The blood and plasma concentration-time curves obtained subsequent to the intravenous administration of trimethoprim lactate solution (TMP 15.3 mg/kg body weight) were fitted to a two-compartment body model (C = Ae(-λ1t) + Be(-λ2t). The rate constants of TMP based on the blood data were λ1: 6.72 ± 2.37 h-1 (mean ± SD); λ2 = 0.898 ± 0.149 h-1; k10: 1.81 ± 0.24 h-1; k12: 2.48 ± 1.25 h-1; k21: 3.34 ± 1.31 h-1 and the volumes of distribution were V1: 1.87 ± 0.21 l and V2: 1.39 ± 0.91 (2.67 ± 0.16 kg body weight). The body clearance of TMP was 1.25 ± 0.12 l/h/kg. The availability of TMP in lactate (TMPL) and in glyconfurol (TMPG) solutions administered to the vastus leteralis muscle was equivalent to that of the intravenous administration at the same dosage. However, the mean absorption time (MAT) of TMP from muscle was significantly shorter with TMPL solution (0.4 ± 0.1 h) than with TMPG solution (1.0 ± 0.1 h). The mean C(max) obtained with TMPL (8.91 ± 1.48 mg/l) was higher than that obtained with TMPG (5.97 ± 0.88 mg/l). The fraction of TMP in the rabbit blood cells averaged 0.388 ± 0.15 (i.v.) and 0.279 ± 0.019 (i.m.).

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