Is the penetration of clindamycin into the masseter muscle really enough to treat odontogenic infections?

Abstract

This study aims to determine the penetration of clindamycin into the masseter muscle of rats by microdialysis and correlate with the main microorganisms involved in odontogenic infections. Tissue concentrations of clindamycin in healthy muscle tissue were measured by microdialysis after administration of a single intravenous dose of 51 mg/kg and multiple doses of 17 mg/kg (8/8 h). It was quantified in plasma after a single administration of 51 mg/kg. Microdialysis samples were collected at 30-min intervals and clindamycin was assayed by LC-MS. Pharmacokinetic parameters and tissue penetration were determined. Pharmacokinetic/pharmacodynamic index (ƒ%T > minimum inhibitory concentration (MIC)) was considered to assess dosing regimens. The pharmacokinetic parameters determined by non-compartmental plasma analysis for the dose of 51 mg/kg were similar to that determined by compartmental analysis. The maximum free interstitial concentration (Cmax) of clindamycin in muscle tissue was 14.20 (10.63-14.89) and 4.82 (3.35-6.66) mg/L for 51 mg/kg and 17 mg/kg 8/8 h, respectively. In addition, the area under the curve (AUC0-inf) for plasma and tissue of clindamycin were 44.78 (28.82-65.65) and 16.54 (13.83-18.35) h.mg/L for 51 mg/kg, respectively, and the tissue penetration factor determined was 1.10. Considering that the main bacteria that cause odontogenic infections generally present MIC ≤ 0.5 mg/L, the ƒ%T > MIC index is reached when the dose regimen of 17 mg/kg 8/8 h is employed. This investigation showed that clindamycin excellently penetrates muscle tissue of rats. It provides effective antibacterial concentrations at the target site when 17 mg/kg 8/8 h is employed and can be applied to treat the main bacteria causing odontogenic infections. It reinforces the use of clindamycin in odontogenic infections with significant tissue penetration.