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Clinical evaluation of metronidazole in gel and tablet formulation in smokers with chronic periodontitis

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Author(s):
Cristiane de Cassia Bergamaschi Motta
Total Authors: 1
Document type: Doctoral Thesis
Press: Piracicaba, SP.
Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Odontologia de Piracicaba
Defense date:
Examining board members:
Francisco Carlos Groppo; Thomaz Wassall; Sinvaldo Baglie; José Ranali; Gilson Cesar Nobre Franco
Advisor: Francisco Carlos Groppo
Abstract

The aim of this study were 1) to compare the effect of metronidazole (Mtz) gel and tablet on debridement periodontal (DP) in smokers; 2) to compare Mtz gel and tablet concentrations in both blood plasma and saliva; 3) to determine the pharmacokinetic profile of Mtz tablet; and 4) to verify the effect of cigarette smoking on bioavailability of Mtz tablet. This study was divided in three chapters. Chapter 1: 30 patients smokers with chronic periodontitis were randomly assigned into 3 groups: PD combined with 3 g placebo gel; PD combined with daily topical application of 3 g Mtz benzoate gel (15%); and PD combined with a daily single dose of 750 mg Mtz (Flagyl®). Clinical parameters evaluated were visible plaque index (VPI), gingival bleeding index (GBI), probing pocket depth (PPD) and relative attachment level (RAL) which were assessed preoperatively, baseline, and after 1, 3 and 6 months after PD. No significant difference was observed among the groups, considering all parameters tested (p>0.05). In all groups was observed a significant reduction in GBI, PPD and RAL, at all times compared to baseline (p<0.05). Chapter 2: 13 volunteers randomly received 750 mg single oral dose FLagyl® and 3 g Mtz benzoate gel (15%). Blood and saliva samples were collected in different times after gel application and oral administration of Mtz. High-performance liquid chromatography (HPLC) was used to quantify plasmatic (PC) and salivary (SC) concentrations of Mtz. Pharmacokinetic parameters determined were: the highest concentration (Cmax), the time at which Cmax ocurred (Tmax), the area under concentration-time curve from zero to infinity (AUC0-¥), the area under concentration-time curve from zero to t (AUC0-t), distribution volume (VD) and renal clearance (CL). Plasma showed higher Mtz concentration from 6 to 24 hours after drug administration and the highest values concerning Tmax, AUC0-48h and AUC0-¥ than those obtained in saliva (p<0.05). No significant difference was observed between SC and PC for Mtz gel considering all periods tested (p>0.05). Chapter 3: 13 smokers (S) and 13 non-smokers (NS) received a single oral dose of 750 mg Mtz tablet. Blood and saliva samples were collected in different times after oral administration of Mtz. HPLC was used to quantify plasmatic and salivary Mtz concentrations. Pharmacokinetic parameters (ASC, Cmax, Tmax, VD and CL) were determined. A significant reduction in plasmatic Mtz concentration was observed in S compared to NS at 1, 1.5 and 2 hours after administration and in Cmax to plasma (p<0.05). No significant difference was observed in Mtz concentration and pharmacokinetic parameters in saliva (p>0.05). Conclusions: 1) Mtz did not improve the clinical outcomes provided by PD alone; 2) Gel and tablet formulations had similar Mtz bioavailability in plasma and saliva; 3) Some pharmacokinetic parameters were higher in plasma than in saliva concerning Mtz tablet. 4) Smoking interfered with the plasmatic Mtz bioavailability but not the salivary. (AU)