Pharmacokinetics of amoxicillin in obese and nonobese subjects

Aims To compare the pharmacokinetics of amoxicillin (AMX) in obese and nonobese subjects, given as single dose 875-mg tablets. Methods A prospective, single-centre, open-label, clinical study was carried out involving 10 nonobese and 20 obese subjects given a dose of an AMX 875-mg tablet. Serial blood samples were collected between 0 and 8 hours after administration of AMX and plasma levels were quantified by liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters (PK) were calculated by noncompartmental analysis and means of the 2 groups were compared using Student t-test. Analysis of correlation between covariates and PK was performed using Pearson's correlation coefficient. Results Ten nonobese subjects (mean age 30.6 +/- 7.12 y; body mass index 21.56 +/- 1.95 kg/m(2)) and 20 obese subjects (mean age 34.47 +/- 7.03 y; body mass index 33.17 +/- 2.38 kg/m(2)) participated in the study. Both maximum concentration (C-max; 12.12 +/- 4.06 vs. 9.66 +/- 2.93 mg/L) and area under the curve (AUC)(0-inf) (34.18 +/- 12.94 mg.h/L vs. 26.88 +/- 9.24 mg.h/L) were slightly higher in nonobese than in obese subjects, respectively, but differences were not significant. The volume of distribution (V/F) parameter was statistically significantly higher in obese compared to nonobese patients (44.20 +/- 17.85 L vs. 27.57 +/- 12.96 L). Statistically significant correlations were observed for several weight metrics vs. AUC, C-max, V/F and clearance, and for creatinine clearance vs. AUC, C-max and clearance. Conclusion In obese subjects, the main altered PK was V/F as a consequence of greater body weight. This may result in antibiotic treatment failure if standard therapeutic regimens are administered.