Pharmacokinetic Analysis of a Single 2000-mg Dose of Metronidazole

Introduction: Evidence suggests that concentrations of metronidazole greater than 20 µg/ml may be required to penetrate bacterial plaque biofilms (Wright et al 1997). Investigation of a treatment strategy based on systemic medication requires a means to evaluate the effects of high concentrations. Objective: To develop methods that measure blood, saliva and gingival crevice fluid (GCF) concentrations following a single 2000 mg oral dose of metronidazole. Methods: After the administration of metronidazole, concentration was measured from blood and saliva samples taken every 15 min for the first 4 hr. Saliva samples were also taken for the next 48 hr. Centrifuged saliva or serum (300 µL) were mixed with 300 µL of acetonitrile, vortexed for 30 sec and kept at 27 C for 15 min and centrifuged (12000xg/10min). GCF samples taken at 0, 0.5, 2 and 4 hr on filter paper strips were eluted with 40 µL of acetonitrile. 20µL aliquots of extracts were injected into the HPLC. Results: Evaluation as a first-order two-compartment model indicated that the concentration of metronidazole in blood reached a maximum of 72.2 µg/ml 0.9 hrs following administration with an absorption half-time (Ta) of 14 min. The concentration in saliva reached a maximum of 25.7 µg/ml 1.6 hrs after administration with a Ta of 17 min. The concentration in GCF reached a maximum of 34.7 µg/ml 1.5 hrs after administration with a Ta of 25 min. The average excretion half-time was 6 hrs. Conclusions: Following a single dose of 2,000 mg of metronidazole, the concentration in blood, GCF and saliva achieved levels that appear sufficient to penetrate dental plaque biofilms.