Effect of bariatric surgery on the pharmacokinetics of drugs used for attention-deficit hyperactivity disorder-A case series

Abstract

Background: Changes in gastrointestinal physiology following bariatric surgery may affect the pharmacokinetics of drugs. Data on the impact of bariatric surgery on drugs used for attention-deficit/hyperactivity disorder (ADHD) are limited.

Methods: In patients treated with ADHD medication and undergoing bariatric surgery, serial drug concentrations were measured for 24 h preoperatively and one, six and 12 months postoperatively. Primary outcome was change in area under the concentration-time curve from 0 to 24 h (AUC_0-24), with other pharmacokinetic variables as secondary outcomes.

Results: Eight patients treated with lisdexamphetamine (n = 4), dexamphetamine (n = 1), methylphenidate (n = 1) and atomoxetine (n = 2) were included. In total, 409 samples were analysed. Patients underwent sleeve gastrectomy (n = 5) and Roux-en-Y gastric bypass (n = 3). AUC_0-24 and C_max of dexamphetamine increased after surgery in those using the prodrug lisdexamphetamine. There was no clear-cut reduction in t_max postoperatively. For ritalinic acid and atomoxetine, no changes in AUC_0-24 were observed, but for atomoxetine, a higher C_max and a shorter t_max were observed postoperatively.

Conclusion: Bariatric surgery may increase the systemic exposure of dexamphetamine after intake of lisdexamphetamine. Patients using lisdexamphetamine should be followed with regard to adverse drug reactions after bariatric surgery, and, if available, therapeutic drug monitoring should be considered.

Keywords: attention‐deficit hyperactivity disorder; bariatric surgery; case series; dexamphetamine; methylphenidate.

FIGURE 1

Individual time‐concentration plots at baseline (preoperatively; red squares) and 1 month (yellow diamonds), 6 months (green circles) and 12 months (brown triangles) postoperatively. In a patient not using the same daily dose during the study, concentrations were adjusted to the main dose for that subject (Table 1). Note that the scale on the y‐axis varies between subjects. RYGB, Roux‐en‐Y gastric bypass; SG, sleeve gastrectomy.

FIGURE 2

Body mass index (BMI), body fat, AUC_0–24, C_max, Cl/F, t_1/2, t_max and V_d/F at baseline (preoperatively) and 1, 6 and 12 months after bariatric surgery in four patients treated with lisdexamphetamine undergoing sleeve gastrectomy (patients 1–3) or Roux‐en‐Y gastric bypass (patient 4), and one patient treated with dexamphetamine undergoing sleeve gastrectomy (patient 5). Values for t_max are not shown for patient 2 and 5 since these patients took their drugs twice daily and the time intervals between intakes varied between study days.

FIGURE 3

Body mass index (BMI), body fat, AUC_0–24, C_max, Cl/F, t_1/2, t_max and V_d/F at baseline (preoperatively) and 1, 6 and 12 month after bariatric surgery in one patient treated with methylphenidate and undergoing sleeve gastrectomy (patient 6), one patient treated with atomoxetine and undergoing sleeve gastrectomy (patient 7) and one patient treated with atomoxetine and undergoing Roux‐en‐Y gastric bypass (patient 8). Values for Cl/F and Vd/F are not shown for patient 6 as the pharmacokinetic variables are presented for the metabolite ritalinic acid.