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.