Pénétration intra-auriculaire d'Augmentin ®: Forme pédiatrique per os (100 mg–12,5 mg/ml d'amoxicilline/acide clavulanique) administrée à la posologie de 80 mg–10 mg kg –1 j –1 en 3 prises

Abstract

Objectives – The authors wanted to assess the pharmacokinetic/pharmacodynamic parameters of Augmentin ® in its pediatric formulation by measuring amoxicillin and clavulanic acid concentration in blood and middle ear fluid. Methods – A multicenter, open pharmacokinetic study, randomized in 5 groups according to sampling time was made on 36 children treated with 80/10 mg kg –1 d –1 for 3 days in 3 intakes per day. Blood and bilateral middle ear fluid samples were drawn simultaneously. Concentrations were measured by HPLC. They were used to calculate amoxicillin and clavulanic acid penetration coefficient in the middle ear fluid; middle ear fluid inhibitory quotient on each sampling; time above MICs according to various MICs; time with middle ear fluid inhibitory quotient above 5; ratio of area under curves to MICs, in both serum and middle ear fluid. Results – Amoxicillin concentrations in middle ear fluid were 7.23, 7.4, 7.08, 6.01, and 3.31 mg/l at respectively 1, 2, 3, 8, and 12h. Serum concentration values ranged from 14.5 mg/l (1 h) to 0.46 mg/l (12 h). For a MIC of 1 mg/l ( S. pneumoniae MIC 90 value), the calculated ratios were : time above MIC of 66% in blood and 100% in middle ear fluid ; inhibitory quotient up to 7.5 in middle ear fluid. Clavulanic acid concentration in middle ear fluid were 0.58, 0.94, 0.62, 0.11, and 0.11 mg/l respectively at the same periods as above. These were above those required in vitro to inhibit beta-lactamase produced by H. influenzae and M. catarrhalis. Conclusion – The studied dosage is adequate for the pharmacodynamic prerequisite of beta-lactams.