Lisdexamfetamine Pharmacokinetic Comparison Between Patients Who Underwent Roux-en-Y Gastric Bypass and Nonsurgical Controls

Abstract

Introduction/Purpose The objective of this research was to characterize the impact of Roux-en-Y gastric bypass (RYGB) on the pharmacokinetic properties of the pro-drug lisdexamfetamine and its active metabolite, d-amphetamine. Materials and Methods A case-control design was used where patients who had undergone RYGB 9-24 months prior were matched on sex, age, and body mass index (BMI) to nonsurgical controls who had no history of weight loss surgery. Each participant received a single 50 mg dose of lisdexamfetamine, and plasma samples were collected over a 24-h period following dosing. Noncompartmental analyses were used to compare pharmacokinetic measures between groups. Results There were no significant differences between the RYGB (n = 10) and NSC groups (n = 10) on sex (70% female), age (40.9 ± 9.6 vs. 41.3 ± 8.9 years), BMI (30.3 ± 5.2 vs. 31 ± 5.9 kg/m 2 ), or ethnicity (100% vs. 80% White). The pharmacokinetic parameters between the RYGB and NCS groups were found to be equivalent for lisdexamfetamine and d-amphetamine, including maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax), and area under the plasma concentration-time curve (AUC (0-∞) ). Conclusion These data suggest that there is no need to routinely adjust lisdexamfetamine dosing following RYGB. However, given the potential for inter-individual differences, patients who undergo RYGB should be clinically monitored and individualized dosing strategies should be considered for concerns surrounding efficacy or toxicity.

Medication and supplement pharmacokinetic changes following bariatric surgery: A systematic review and meta‐analysis

“…We included 30 studies 30,32,37,39,40,56–58,60–74,76–80,82,83 reporting on PK outcomes of oral bioavailability following metabolic surgery (RYGB or BPD) with a total of 33 medications and 430 participants ( Table 3 ). A majority of studies did not report significant changes in oral absorption following metabolic surgery.…”

“…Overall, 24 studies 30,33–54 including a total of 1,427 participants could be used to conduct a meta‐analysis on the post‐operative PK parameters of the following oral medications and supplements: atorvastatin, paracetamol, omeprazole, midazolam, vitamin D, calcium, zinc, and iron supplements. The remaining 34 studies 30,32,41,42,44,55–84 (558 participants in total, 37 different drugs, and 4 supplements) were included in a systematic review.…”

“…Absorption (estimated using AUC and/or C max ) remained unchanged following bariatric surgery for most medications, except for 1) carbamazepine, whereby levels decreased following SG, 59 2) tacrolimus, where C 0 increased from 9 to 12 months post-operatively (n = 12, patients in chronic renal failure), 75 3) rivaroxaban, where C max increased when assessed shortly after SG (n = 6, measured between 1-and 3-days post-op), 77 but only in one study. 85 We included 30 studies 30,32,37,39,40,[56][57][58][60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][76][77][78][79][80]82,83 reporting on PK outcomes of oral bioavailability following metabolic surgery (RYGB or BPD) with a total of 33 medications and 430 participants (Table 3). A majority of studies did not report significant changes in oral absorption following metabolic surgery.…”

The Influence of a Roux-en-Y Gastric Bypass on Plasma Concentrations of Antidepressants

“…Several reports have been published regarding the altered pharmacokinetics of psychotropic treatments such as haloperidol, lithium, lurasidone, long-acting paliperidone, or lisdexamfetamine [7][8][9][10]. Data regarding antidepressants are very scarce compared to the widespread use of this therapeutic class.…”

High-dose stimulants for adult ADHD

“…Plasma levels have not been shown to be helpful in guiding methylphenidate or amphetamine treatment selection or dosing Liquid stimulant formulations may be an option for patients experiencing medication malabsorption lisdexamfetamine dosing following Rouxen-Y gastric bypass surgery is unnecessary, there may be interindividual differences, and individualized dosing regimens may be needed. 16 When managing patients who might be experiencing medication malabsorption, it may be helpful to use dosage forms that avoid disintegration, acidic environments, and slow dissolution. Because they are more rapidly absorbed and not susceptible to disintegration and dissolution, liquid formulations are recommended.…”