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A comparison of the pharmacokinetics of oral metronidazole, after a single dose of 30 mg/kg body weight, was done in two groups of subjects: group I consisted of 10 severely malnourished children, aged 4 to 43 months; group II consisted of 10 children, aged 3 to 25 months, who were studied after nutritional rehabilitation. The biologic half-life of elimination was significantly longer (p less than 0.01) in severely malnourished children (median, 10.21 hours; range, 4.89 to 22.93 hours) than in rehabilitated children (median, 5.09 hours; range, 2.61 to 8.75 hours). Metabolic clearance of metronidazole was significantly lower in group I (p less than 0.01; median, 0.077 L/kg/hr; range, 0.033 to 0.192 L/kg/hr) than in nutritionally rehabilitated children (median, 0.166 L/kg/hr; range, 0.105 to 0.300 L/kg/hr). Volume of distribution was not different between groups I and II, although both showed higher values than the values reported for children who were not malnourished. These findings suggest that the dose of metronidazole should be reduced in malnourished children, and the therapeutic regimen should be individualized for each patient.

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The use of metronidazole for the treatment of intestinal parasitosis has increased markedly, particularly in developing countries, where the association of malnutrition and parasitosis is very common. Since biotransformation of metronidazole is significantly affected by severe malnutrition, and undesirable effects of the drug seem to be related to its plasma concentration, it was decided to carry out a study to establish a dosing-regimen of metronidazole in severely malnourished children. A single dose of 30 mg/kg body weight, and computer simulation of a steady-state was studied in 10 malnourished and in 10 patients undergoing nutritional rehabilitation. Due to ethical considerations (refusal of parents to allow a second dose of metronidazole) acute malnourished children and rehabilitated patients are 2 distinct groups. The results indicate that a predicted drug cumulation would occur in malnourished children with the ordinary dosage regimen (30 mg/kg/day). Based on the clearance data, daily maintenance doses for pediatric patients with severe malnutrition should be 12.0 mg/kg/day, corresponding to a 60% reduction of the common dose calculated to achieve and maintain a plasma concentration of 6.0 micrograms/ml of metronidazole. The study illustrates the need for pharmacokinetic data to establish the individual dose of a drug particularly under conditions that alter biotransformation processes.