Disintegration of the oral drug formulation
The first step in the absorption of solid formulations like tablets and capsules, is disintegration in the GI tract. Disintegration is affected by several variables, such as gastric volume and mixing, which can be both diminished after bariatric surgery 15,16. Due to a reduced volume, it is often assumed that tablets, may not fully dissolve, resulting in altered exposure of the drug17,18. For this reason, administration of oral liquids is often proposed after bariatric surgery, even though hard evidence to support this statement is lacking. A disadvantage of liquid formulations like suspensions is that these formulations may contain sugars, which may, in large amounts, lead to the dumping syndrome19.
Montanha et al. investigated the effect of RYGB on the bioavailability of amoxicillin tablets versus suspension 20. A lower Area Under the Curve (AUC) for tablets (23.10 ± 7.41 mg.h/L) was found as compared to the suspension (27.59 ± 8.32 mg.h/L) , corresponding to a relative biological availability of 83%. The higher AUC of the suspension resulted from a higher Cmax (8.73 ± 3.26 vs 7.42 ± 2.99 mg/L) and lower Tmax compared to tablets (1.7 ± 0.86 vs 2 ± 0.76 hours). While no clinical outcome measures were reported, for both formulations, the time above the minimum inhibitory concentration (MIC) for pathogens with an MIC <4mg/l was attained, and therefore effectiveness seems to be guaranteed for both oral drug formulations.
Schulman et al. investigated the effect of RYGB surgery on Proton Pump Inhibitor (PPI) in Open Capsule (OC) versus Intact Capsule (IC) form21. They showed a significantly shorter healing time (median healing time of 91 days vs. 342 days) in the OC PPI group compared to the IC PPI group. There was, however, a significantly larger percentage of sucralfate use in the OC group and a larger non-significant percentage non-steroidal anti-inflammatory drug (NSAID) use in the IC group, which may have contributed to the reported difference in effect 21.
From these reports, it seems that suspensions may lead to a higher exposure but may not always be preferable because of sugar loads, and that open capsules may lead to more effective treatment than intact capsules after RYGB surgery. With increased exposure upon the use of the amoxicillin suspension, earlier and higher peak concentrations were observed. Such early and high peak concentrations may be undesirable for certain drugs like morphine, for which upon use of an oral solution yielded a three-fold increased Cmax, lower Tmax and increased AUC at six months after bariatric surgery 22. Additionally, midazolam was reported to have an earlier and 1.5 fold higher peak concentration after oral administration 23.