Pharmacokinetics of metronidazole in patients with enteric disease compared to normal volunteers

Abstract

Tablets of 500 mg metronidazole were given to 24 patients with intestinal diseases and to 10 healthy volunteers. The diagnoses included coeliac disease, ulcerative colitis, jejunoileal shunt, ileostomy, and Crohn's disease. Both normal subjects and patients exhibited considerable variation in serum metronidazole concentrations. This applied particularly to the patients who had somewhat slower absorption and later occurrence of serum peaks than did the normal subjects. No major deviation occurred within any of the diagnostic groups. All but the ileostomy patients exhibited a lag before apparent absorption. The individual peaks occurred after 1.5-2.0 h and was 12.7 +/- 2.1 microgram/ml in all disease groups, except the ileostomy patients who exhibited a mean of 16.2 microgram/ml. In the healthy subjects, the mean peak was 12.1 +/- 4.6 microgram/ml. A major finding was the observation that the patients as a group had a higher total area under the serum curves (AUC) than the volunteers. The AUC of normal volunteers was 108.1 microgram . h . ml-1 compared to 260.5 microgram . h. ml-1 in the patients with ileostomy and 147.6 microgram . h . ml-1 for the others. The higher AUC values in the ileostomy group were associated with longer serum half-life values. The serum half-life was 8.3 in the normals, 11.9 with ileostomy and 7.2 h in the remainder. The normal individuals and the patients with ulcerative colitis had higher rates of absorption, those with coeliac disease or ileostomy lower absorption rates than was found elsewhere. The relative volume of distribution (the distribution coefficient) was the same in the healthy individuals as in each patients group, except for the ileostomy patients. The total body clearance was 1.94 liters/h in ileostomy, 3.68 liters/h in the other patients, and 5.43 liters/h in the normal subjects.