Abstract
We investigated the effects of antibacterial and nonsteroidal anti-inflammatory drugs [bacampicillin (BAPC), cefaclor (CCL), acetylsalicylic acid (ASA), indomethacin (IDM)] in different diets on pharmacokinetics in young rats with malocclusion. Five-week-old male Wistar rats were divided into groups of 8 and fed a solid (Solid-G) or mud (Mud-G) diet for 10 weeks. All molars in rats receiving Mud-G were extracted to induce malocclusion. BAPC and CCL concentrations in rat plasma after oral administrations of those (20 mg/kg) were measured using a paper disk method. The plasma concentration of the unchanged form was determined serially by HPLC for 12 hours after a single oral dose of ASA (20 mg/kg) and IDM (10 mg/kg). For pharmacokinetic analysis, BAPC, CCL, and ASA in a one-compartment model, and IDM in a two-compartment model were applied to the time course of plasma levels. Values for the following pharmacokinetic parameters were obtained. BAPC : Cmax (6.85 μg/ml) of Mud-G was significantly higher than that of Solid-G (5.34 μg/ml,p＜0.01), Tmax of Solid-G and Mud-G was 23.3 and 37.5 minutes, respectively, and AUC of Solid-G and Mud-G was 10.4 and 14.5 μg・hour/ml, respectively. CCL : Cmax (7.17 μg/ml) of Mud-G was significantly higher than that of Solid-G (5.44 μg/ml,p＜0.01), Tmax of Solid-G and Mud-G was 44.4 and 51.0 minutes, respectively, and ke of Solid-G and Mud-G was 1.14 and 0.69 hours-1, respectively. The levels of Cmax, Tmax, t1/2, and AUC in the pharmacokinetics of ASA and IDM in Mud-G were higher than that of Solid-G, while ASA and IDM in Mud-G were not significantly different than those of Solid-G. Furthermore, Cmax, Tmax, t1/2, and AUC levels in the pharmacokinetics of BAPC and CCL with Mud-G showed a remarkably significant increase in comparison with Solid-G, while there was no significant difference regarding ASA and IDM observed between Solid-G and Mud-G. These results suggest that a high drug concentration in plasma and slow disappearance resulted in a longer duration with the Mud-G diet.
