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.