Pharmacokinetics of a new oral formulation of amoxicillin

Abstract

The bioavailability of the recently developed 1 g dispersible tablet form of amoxicillin (B) and the 1 g dispersible tablet in suspension form (C) were compared to that of the 1 g standard reference formulation (A). Twelve healthy volunteers were involved in this single-dose, open, randomized, three-way cross-over study. The mean peak serum levels were 14.1 +/- 4.1 micrograms/ml after A, 15.1 +/- 3.1 micrograms/ml after B and 15.1 +/- 5.4 micrograms/ml after C. The area under the drug concentration versus time curves were 47.6 +/- 12.0 micrograms.h/ml after A, 52.8 +/- 10.2 micrograms.h/ml after B and 51.1 +/- 13.8 micrograms.h/ml after C. On the basis of these two pharmacokinetic parameters, the three formulations were found to be bioequivalent. In addition, the predicted serum concentrations during multiple dosing (3 times a day), derived from the corresponding mean concentrations after a single 1 g dose of C showed that 8 hourly administration would yield therapeutic serum concentrations for infections such as uncomplicated community-acquired pneumonia due to susceptible or less susceptible strains in otherwise healthy subjects.

Development and Validation of Limited-Sampling Strategies for Predicting Amoxicillin Pharmacokinetic and Pharmacodynamic Parameters

“…A large number of plasma samples (n ϭ 1,152) collected from 48 closely monitored, healthy volunteers in two bioequivalence studies allowed the development and subsequent validation of LSS models by using several different procedures. The results show that the AUC 0-ϱ of amoxicillin, following administration of single oral doses (500 ) for amoxicillin in 11 previously published studies (1,3,7,10,13,14,(17)(18)(19)(20)26), and the corresponding AUC 0-ϱ derived from the three-point LSS model developed for the reference capsule formulation in the present study (Table 3, (Table 2). The statistical principle of parsimony advises in favor of models with fewer parameters; thus, we settled for three-sample regressions for independent estimation of amoxicillin's AUC 0-ϱ .…”

“…The robustness of the three-point LSS regression equation derived from the capsule formulation data set as a predictor of the plasma amoxicillin AUC 0-ϱ was confirmed when tested on data from 11 published studies (1,3,7,10,13,14,(17)(18)(19)(20)26), encompassing a large range of amoxicillin single doses (250 to 1,000 mg) and AUC 0-ϱ 's (9 to 55 g ⅐ h ⅐ ml Ϫ1 ). This result not only validates our proposed three-point LSS model but also extends its applicability to a variety of experimental conditions, both clinical and analytical, which prevailed in the 11 studies examined.…”

“…Amoxicillin concentrations were determined by a validated microbiological method (agar well diffusion) using Micrococcus luteus (ATCC 9341) as the test organism (6,20) and Antibiotic Medium 2 (Difco Laboratories). Fresh stock solutions of amoxicillin at 1,000 g/ml were made up in 0.1 M phosphate buffer (pH 6.0) for each set of assays.…”

“…As a third test of the validity of the LSS models developed for estimating amoxicillin's AUC 0-ϱ , the most informative three-point LSS equation derived for the training data set (reference capsule formulation) was used to estimate the AUC 0-ϱ of subjects enrolled in 11 previously published studies after administration of single oral doses (250 to 1,000 mg) of various amoxicillin formulations (1,3,7,10,13,14,(17)(18)(19)(20)26). Scanned plots of the published AUCs were used to obtain the data points employed for the LSS-derived AUC 0-ϱ 's and to obtain the best estimated AUC 0-ϱ 's by means of the trapezoidal method.…”

Comparative Pharmacokinetics of Two Tablet Formulations of Amoxicillin: Bioequivalence Assessment

“…The drug is generally active against Gram-negative and Gram-positive susceptible bacteria. The antibacterial activity furthermore encompasses microorganisms commonly involved in infections of the skin, soft tissue, urinary tract and upper respiratory tract [1].…”