Hundreds of blood samples can describe individual concentration curves in detail without creating a large patient population. A case series published online in 2024, with a 2025 issue date, illustrates that distinction in research on ADHD medicines after bariatric surgery.
How many patients contributed the samples?
Krabseth and colleagues analyzed 409 samples from eight patients: four taking lisdexamfetamine, one dexamphetamine, one methylphenidate and two atomoxetine. Five underwent sleeve gastrectomy and three Roux-en-Y gastric bypass. The central amphetamine finding concerned the four prodrug-treated patients, rather than all eight participants or 409 independent people.
Serial serum measurements covered 24 hours before surgery and at one, six and twelve months afterward. For lisdexamfetamine, the measured analyte was active dexamphetamine, not the intact prodrug. The primary endpoint was change in area under the serum concentration–time curve over 0–24 hours.
What exposure patterns were observed?
Dexamphetamine exposure increased after surgery in the four lisdexamfetamine patients. The authors described increases of roughly 50%–100% in two and approximately 30% in the other two. Peak concentrations also increased. There was no clear-cut shortening of time to peak, and reliable timing data were limited by twice-daily dosing in some patients.
No corresponding increase in exposure area was observed in the one participant taking dexamphetamine directly. That single observation is an important contrast, but it cannot establish a reliable difference between formulations or identify a prodrug-specific mechanism.
Were the doses fixed?
The four lisdexamfetamine regimens began at 100 mg once daily, 30 mg twice daily, 50 mg once daily and 30 mg once daily. The 50-mg regimen increased to 60 mg at twelve months. Three of these patients underwent sleeve gastrectomy and one gastric bypass.
When daily doses changed, the investigators adjusted concentrations to the main dose for that patient before calculation, assuming linear pharmacokinetics. The resulting comparisons therefore included a modeling assumption. They should not be described as entirely unadjusted observations after identical doses at every visit. The reported regimens are study histories, not prescribing guidance.
Did surgery itself cause the increase?
The longitudinal design compared each person with their own preoperative profile. That reduces some between-person differences, but surgery was accompanied by weight loss and changes in body composition. There was no comparison group losing weight through other means.
The authors could not distinguish the operation’s effects from those accompanying changes. They discussed absorption and elimination hypotheses, but did not experimentally isolate a transporter mechanism or measure a causal urinary-pH pathway in these patients.
What can repeated sampling establish?
Repeated measurements help estimate peak concentration, timing and exposure area for a particular observation period. They do not supply independent replications of surgery in new people. With four lisdexamfetamine patients, a large-looking laboratory workload cannot support a precise population effect estimate.
The investigators accordingly presented descriptive statistics rather than a definitive statistical comparison for each drug. The approximate percentage changes should remain individual observations, without an invented confidence interval or claim of a universally doubled exposure.
What is useful for a toxicology review?
The study challenges an automatic assumption that bariatric surgery must reduce oral-drug exposure. It does not establish that exposure always rises, specify an individual’s postoperative dose, or connect serum changes directly to impairment. A case-specific review should retain the drug formulation, actual dosing schedule, serum analyte, operation type, time since surgery and dose-normalization method.
Source
Krabseth HM, Strømmen M, Helland A, Spigset O. Effect of bariatric surgery on the pharmacokinetics of drugs used for attention-deficit hyperactivity disorder—A case series. Basic & Clinical Pharmacology & Toxicology. 2025;136(1):e14099. Published online November 4, 2024. DOI: 10.1111/bcpt.14099. Full text; bibliographic record.