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%).