Pharmacokinetics and Tissue Distribution of Amoxicillin plus Clavulanic Acid after Oral Administration in Man

Abstract

Augmentin (875 amoxicillin and 125 mg potassium clavulanate) was administered orally to patients with chronic bronchitis. Concentrations of amoxicillin and clavulanic acid were measured in serum, sputum and urine. Peak serum levels for amoxicillin of 11.23 +/- 2.61 micrograms/ml were observed at 2 hours and for clavulanic acid of 2.55 +/- 0.54 micrograms/ml at 1 hour. After 9 hours, 50% of the amoxicillin and 39% of the clavulanic acid had been renally excreted. The peak sputum concentration of amoxicillin was 1.31 +/- 0.42 micrograms/ml at 4 hours and of clavulanate was 0.79 +/- 0.23 micrograms/ml at 2 hours. Patients awaiting surgery received an oral dose of augmentin as above. Samples of lung, tonsil, middle ear mucosa and prostate were obtained and tissue concentrations of both compounds measured. Peak levels of amoxicillin ranged from 0.87 micrograms/g (tonsil) to 2.56 micrograms/g (lung) and of clavulanic acid from 0.20 micrograms/g (prostate) to 0.56 micrograms/g (lung) between 3 and 4 hours after dosing.

Evaluation of amoxicillin plasma and tissue levels in pediatric patients undergoing tonsillectomy

“…Serum amoxicillin concentration found in this study is comparable to levels previously reported [18][19][20][21]; however, what is remarkable here is the high prevalence of children with low plasma levels. Although delays in collecting blood samples cannot be excluded, we ascribe it to a low compliance of the patient to the chemoprophylaxis protocol (i.e.…”

“…Department of ''Amedeo Avogadro'' University of Eastern Piedmont in Novara for elective tonsillectomy. All tonsils were removed by cold dissection tonsillectomy, with a mean surgery time of 20 min (range [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]. Previously, patients were treated with 3 doses of amoxicillinclavulanic acid given orally the day before plus a further dose given 2 h before admittance into the operating theatre.…”

“…Since few previous studies have assessed the effectiveness of prophylaxis by direct measurement of antibiotic levels both in plasma and tissue [18][19][20][21], we designed an experimental study to quantitatively evaluate amoxicillin concentrations in children ready for tonsillectomy and to compare these plasma and tissue levels with the Minimal Inhibitory Concentrations (MIC) of the bacteria more commonly involved in the upper airways infections.…”

β-Lactam Activity against Penicillin-Resistant <i>Streptococcus pneumoniae</i> Strains Exhibiting Higher Amoxicillin versus Penicillin Minimum Inhibitory Concentration Values: An in vitro Pharmacodynamic Simulation

“…against strain 2, between cefditoren and all other regimens against strains 3 and 4, and between cefuroxime versus both amoxicillin/clavulanic acid regimens against strain 3. Table 2 shows T 1 MIC and log 10 reductions at selected timepoints (8,12 and 24 h), together with the maximal reduction obtained. Bactericidal activity ( 6 3 log 10 reduction) at 12 and 24 h was obtained against all strains with cefditoren, against strains 1 and 2 with cefuroxime and amoxicillin/clavulanic acid t.i.d., but only against strain 1 with amoxicillin/clavulanic acid b.i.d.. Bactericidal activity at 24 h was obtained when T 1 MIC was 1 30% of the dosing interval, a reduction of 1.7-2.0 log 10 was obtained with T 1 MIC of 20-30%, and !…”

“…[10][11][12][13] were simulated over 24 h. The target total drug pharmacokinetic parameters, based on mean values reported in humans, were as follows: C max = 4.20 g/ml, T max = 2.75 h, and t 1/2 = 1.55 h for cefditoren [6,7] , and C max = 7.70 g/ml, T max = 3.0 h, and t 1/2 = 1.10 h for cefuroxime [8] . For the amoxicillin/clavulanic acid combinations, the half-life and T max of clavulanic acid were employed: T max = 1.0 h, and t 1/2 = 1.1 h [10,11] ; the target C max for amoxicillin was 10.30 g/ml [10,12,13] and for clavulanic acid 2.40 g/ml [10,11] .…”