The effect of a gastric bypass on the pharmacokinetics of citalopram

Rationale: Psychiatric disorders, including depression, are common in people
with morbid obesity. The Roux- and Y gastric bypass (RYGB) operation causes a
drastic change in the gastrointestinal tract, which may lead to a change in
drug levels. Possibly the changing conditions for drug dissolution and a
decrease of absorption in the intestinal area may play a role. Some small-scale
studies show that bioavailability decreases in some drugs. However, there is
insufficient data available on the effect of a gastric bypass surgery on the
pharmacokinetics of citalopram. Further research is needed to adequately map
the effect of a RYGB operation on the pharmacokinetics, so that optimal
pharmacotherapy treatment can be given to patients after a bariatric procedure.

Primary objective: Determine whether a RYGB operation causes a clinically
significant decrease in AUC (area under serum concentration-time curve) of
citalopram three months after surgery in comparison with the situation before
the operation.

Secondary objectives:
Validation of the pharmacokinetic model of citalopram (based on data from the
CITA I study) in obese and bariatric patients with the optimal sampling
strategy created from this data. Determine whether the citalopram
pharmacokinetic parameters Cmax (maximal concentration), Tmax (time of maximal
serum concentration) and T1/2 (half-life)) of citalopram before and after
surgery differ significantly after one and three months compared to the
situation before RYGB. Compare the citalopram trough levels after one and three
months to the trough levels before the RYGB.

Study design: pre- / post study; Prospective, observational research.

The burden of participation in the study is high for the participants. In
total, they will spend three days in the Maasstad Ziekenhuis or the Franciscus
Gasthuis. The preoperative visit and the visit one month postoperatively are
additional visits for the patient. Participation in this study three months
postoperatively is combined with the regular follow-up of the surgeon and
dietician.


De bloedafname zal plaatsvinden volgens de venapunctie methode of de venflon
methode. Hieronder zullen de twee methodes worden toegelicht.

Venapunction method
On the research day the participant will receive a venapunction at three
different times during each research day, 4 ml of blood will be taken at these
times. In this way the participant is not burdened with a venflon and there is
no risk of clogging of the venflon.

Venflon method
On the research day the participant will receive a venflon. In this way, the
participant only has to be injected once. Blood samples are taken via the
venflon. 4 ml of blood will be taken at three different times during each
research day.

Risks of participation in the research are small for the participants: research
is done with a registered drug whose dose and composition will not be adjusted
for the study. Chances of AEs and SAEs are not greater than in standard
treatment. The results of this research may provide data that may lead to new
pharmacological insights and further scientific research.