DISPOSITION OF INTRAVENOUS METRONIDAZOLE IN ASIAN SURGICAL PATIENTS

Steady-state peak and trough concentrations of metronidazole and its m etabolites were measured in the sera of 54 surgical patients who were on intravenous metronidazole, 500 mg every 8 h, These patients had no significant renal or hepatic impairment, High-pressure liquid chromato graphy was used to determine the concentrations of metronidazole and i ts metabolites, The mean peak and trough metronidazole concentrations were 28.9 +/- 11.0 and 18.0 +/- 9.9 mu g/ml, respectively. The acid me tabolite was not detectable in all the blood specimens, The mean peak concentration of the hydroxy metabolite (MH) was 6.6 +/- 4.3 mu g/ml, the mean trough concentration of MH was 6.2 +/- 4.2 mu g/ml, and the M H concentration/metronidazole concentration ratio was 0.4 +/- 0.24, Us ing a population-based method for the pharmacokinetic analysis and ste pwise regression between parameters and covariables (sex, age, and wei ght), we found that weight showed the highest correlation with the tot al body clearance (CL), The mean CL was 0.89 +/- 0.3 ml min(-1) kg(-1) (3.029 liters/h), the mean volume of distribution was 0.73 +/- 0.14 l iter/kg, and the mean elimination half-life was 10.6 +/- 4.5 h, For th e patients in our study, the CL was lower and the elimination half-lif e was longer compared with those for healthy volunteers, but the value s of these parameters were comparable to those found for hospitalized patients, There was an inverse correlation between age and CL.