Comparative Pharmacokinetics of Metronidazole and Tinidazole and Their Tissue Penetration

Abstract

Since metronidazole and tinidazole are used prophylactically against infections after colorectal surgery, their pharmacokinetics and that of hydroxy-metronidazole were compared in 34 such patients. Seventeen patients received a single dose of 1.5 g (50-min infusion) of either agent 1 h before the operation. The concentrations of serum and tissue homogenates (subcutaneous fat, omentum, peritoneum, ileum, appendix, colon) were assayed by high-pressure liquid chromatography. The serum concentrations 1 h after start of infusion were 34.1 ± 6.7mg/l of metronidazole, 2.3 ± 1.2 mg/l of OH-metronidazole, and 35.2 ± 6.3 mg/l of tinidazole. OH-metronidazole and tinidazole were detectable for 72 h and metronidazole for 48 h. The ranges of serum and tissue concentrations (subcutaneous fat, omentum, peritoneum, ileum, appendix, colon) overlapped (within one single standard deviation). The tissue concentrations were high, particularly in intestinal tissues, except that the levels were low in subcutaneous tissue. The serum half-life of metronidazole was 9.0 ± 1.6 h, of OH-metronidazole 14.8 ± 7.4 h, and of tinidazole 16.4 ± 3.8 h. The terminal-phase distribution volume was 35.8 ± 10.01 for metronidazole and 40.6 ± 9.91 for tinidazole, and the total body clearance 2.7 ± 1.2 1/h and 1.8 ± 0.5 1/h, respectively. The slower disposition of OH-metronidazole, which inhibits anaerobic bacteria, prolongs the duration of bioactivity in the body after metronidazole to that reached by tinidazole. OH-tinidazole was not detected in patient specimens (assay standards ensured that it could be assayed). The suitability of 1.5g of metronidazole or tinidazole prophylactically follows from the present demonstration that serum and tissue levels would remain above the minimum inhibitory concentration of relevant target organisms for 48–72 h.

Key Words:

• Intestinal surgery
• metronidazole
• pharmacokinetics
• prophylaxis
• tinidazole