Beta-lactam antibiotics (amoxicillin, penicillin and ampicillin)
To date, five studies have been published regarding the pharmacokinetics of oral beta-lactam antibiotics. Two studies, i.e. Terry et al. and Miskowiak et al., describe the pharmacokinetics of oral phenoxymethylpenicillin after gastroplasty and jejunoileal bypass, procedures that are to date not often applied any more44,45. Miskowiak et al. evaluated the effect of gastroplasty on the absorption of phenoxymethylpenicillin when given as a non-coated tablet or as an aqueous solution (one-week washout) in eight female bariatric surgery patients before and three months after gastroplasty surgery. In this study, no significant changes in plasma concentrations, Cmax, T1/2, Tmax and AUC were found before versus after surgery. 44. There were also no significant differences in AUC between tablet and aqueous solution. Terry et al. studied the oral absorption of a single administration of 1 gram phenoxymethylpenicillin in three subjects before and three months after jejunoileal bypass and in five subjects three months after jejunoileal bypass 45. In the group with AUC measurements before and after surgery, a substantially increased AUC after surgery (176.8 ± 98.1 vs. 17.1 ± 5.9 units/ml * hour) was demonstrated. However, in the group where AUC was only measured after surgery, the AUC was 46.2 ± 30.4 units/ml * hour, illustrating a large interindividual variability in the AUC after jejunoileal bypass surgery. Peak serum concentration also increased significantly. The authors explained the enhanced absorption of penicillin by the lack of degradation which generally occurs in acid gastric contents.
The pharmacokinetics of oral amoxicillin after RYGB surgery was studied by Rocha et al. and Montanha et al. 46,47. Rocha et al. studied eight obese subjects receiving an amoxicillin 500mg capsule before and two months after RYGB surgery 47. They found a large and significant rise in AUC (7.21 ± 5.13 vs. 2.03 ± 0.77 ug.h/ml) and Cmax (1.77 ± 1.19 vs. 0.62 ± 0.22) after surgery whereas Tmax and t1/2 were not significantly altered. All of these values were however substantially lower compared to non-obese subjects who had AUCC0–tlast values of 12.44 – 12.05 ug.h/ml and a Cmax ranging from 4.94 to 5.31 ug/ml.
As previously stated, Montanha et al. reported a higher AUC for amoxicillin suspension compared to amoxicillin tablets in 20 RYGB surgery patients 46. This higher AUC was predominantly explained by the higher Cmax observed after the suspension. When comparing these results to amoxicillin absorption rates in non-bariatric and non-obese subjects, the total absorbed amount of amoxicillin appeared 40% lower the suspension group and 50% lower for the tablets. Even though no clinical outcome measures were reported, for both formulations, the time above the MIC for pathogens with a MIC <4mg/l was attained in the study of Montanha et al. Therefore, it seems that oral amoxicillin can be used in post RYGB surgery patients, despite the fact that the AUC is lower in comparison to normal weight subjects.
Kampmann studied oral absorption of ampicillin in six patients with morbid obesity undergoing jejunoileostomy 48. Before surgery and 1-2 weeks, 6 months and 12 months postoperatively, patients received 500 mg ampicillin intravenously and 700 mg of oral pivampicillin (the pivaloylmethylesther of ampicillin) on separate days. A significant decrease in bioavailability was reported at 1-2 weeks (65 ± 18%), 6 months (66 ± 36%) and at 12 months (41 ± 30 %) after surgery compared to preoperative bioavailability (109 ± 44 %). However, as the bioavailability in healthy normal-weight subjects was 50%, these lower values might not have implications for antibiotic therapy. The authors suggest that the impeded absorption compared to pre-surgery in morbidly obese patients which may have several explanations including: a change in bile acid metabolism; an increased number of enterobacteriae; premature splitting of the lipophilic part of pivampicillin; and/or an elevated mucosal enzyme level participating in the hydrolysis of pivampicillin 48. No explanations were given for the higher bioavailability of pivampicillin in morbidly obese patients before surgery compared to healthy volunteers (109 vs 50%).