Salivary pharmacokinetic of metronidazole in smokers and non-smokers

Objectives: To evaluate the effect of smoking on the bioavailability of metronidazole. Methods: Twelve heavy-smokers (Group 1) and twelve non-smokers (Group 2) subjects received a single 750-mg oral dose of metronidazole. Saliva samples (1 ml) were collected at 0, 30min, 1h, 1h30min, 2h, 4h, 6h, 8h and 12h after drug administration. High-performance liquid chromatography (HPLC) with UV detection was used to quantify salivary metronidazole concentrations. The chromatographic separations were carried out using a Lichrospher column 100 RP18 (125mm x 4mm x 5µm, Merck, Darnstadt, Germany). The samples were submitted to extraction by using perchloric acid solution. The mobile phase consisted of aqueous solution of 0.01M sodium monophosphate (pH=4.7) and acetonitrile (85:15 v/v). The flow-rate was 1.0mL/min and the wavelength was set at 320nm. The pharmacokinetic parameters AUC, Cmax and Tmax were analyzed by Wilcoxon test (p<0.05). Results: For Group 1 (median, 1st – 3rd quartiles) AUC0-12, Cmax and Tmax values were 3.4 (3.2 - 4.2) µg-min/ml, 7.7 (6.2 - 9.8) µg/ml and 90 (60 - 120) min, respectively, and for Group 2, 3.4 (2.2 - 5.3) µg-min/ml, 8.0 (4.6 - 13.7) µg/ml and 90 (75 - 120) min. The pharmacokinetic parameters showed no statistically significant differences (p>0.05) between the two groups. Conclusion: Smoking does not interfere in the bioavailability of metronidazole in saliva. Supported by FAPESP #07/50427-0.