Pharmacokinetics in Morbid Obesity: Influence of Two Bariatric Surgery Techniques on Paracetamol and Caffeine Metabolism

Arnó, Albert Goday; Farré, Magı́; Rodríguez-Morató, José; Ramón, José́; Pérez‐Mañá, Clara; Papaseit, Esther; Civit, Ester; Langohr, Klaus; Carbó, Marcel·lí; Benaiges, David; Castañer, Olga; Roux, Juana Antonia Flores Le; Pera, Manuel; Grande, Luís; Torre, Rafael de la

doi:10.1007/s11695-017-2745-z

Cited by 24 publications

(43 citation statements)

References 23 publications

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“…No differences were observed between the two surgical methods. Another interesting finding was that the patients with morbid obesity also had lower C max and AUC of paracetamol compared with normal weight individuals before surgery . Six months following surgery, the C max and AUC were, however, similar to that of normal weight individuals.…”

Section: Resultsmentioning

confidence: 92%

“…In most studies, the patients undergoing surgery served as their own controls. Two studies also included control groups of healthy volunteers …”

Section: Resultsmentioning

confidence: 99%

“…RYGBP was the predominant surgical procedure (n = 18) . In one study, BPD was investigated as the surgical procedure, while two studies investigated BPD‐DS, six studied SG, and one included jejunoileostomy …”

Section: Resultsmentioning

confidence: 99%

“…Among the 22 studies, 16 utilized a single‐dose design, administering a given dose of the studied drug on the day of the pharmacokinetic study intervention. In the remaining six studies, patients were investigated in steady state .…”

Section: Resultsmentioning

confidence: 99%

“…Paracetamol is a widely recognized probe for gastric emptying . The effects of SG and RYGBP on paracetamol pharmacokinetics were reported in a prospective single‐dose study before versus 4 weeks and 6 months after surgery . At both postoperative time points, AUC and C max increased, and T max decreased after 6 months.…”

Section: Resultsmentioning

confidence: 99%

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The influence of bariatric surgery on oral drug bioavailability in patients with obesity: A systematic review

et al. 2019

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Summary Anatomical changes in the gastrointestinal tract and subsequent weight loss may influence drug disposition and thus drug dosing following bariatric surgery. This review systematically examines the effects of bariatric surgery on drug pharmacokinetics, focusing especially on the mechanisms involved in restricting oral bioavailability. Studies with a longitudinal before‐after design investigating the pharmacokinetics of at least one drug were reviewed. The need for dose adjustment following bariatric surgery was examined, as well as the potential for extrapolation to other drugs subjected to coinciding pharmacokinetic mechanisms. A total of 22 original articles and 32 different drugs were assessed. The majority of available data is based on Roux‐en‐Y gastric bypass (RYGBP) (18 of 22 studies), and hence, the overall interpretation is more or less limited to RYGBP. In the case of the majority of studied drugs, an increased absorption rate was observed early after RYGBP. The effect on systemic exposure allows for a low degree of extrapolation, including between drugs subjected to the same major metabolic and transporter pathways. On the basis of current understanding, predicting the pharmacokinetic change for a specific drug following RYGBP is challenging. Close monitoring of each individual drug is therefore recommended in the early postsurgical phase. Future studies should focus on the long‐term effects of bariatric surgery on drug disposition, and they should also aim to disentangle the effects of the surgery itself and the subsequent weight loss.

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Section: Resultsmentioning

confidence: 92%

“…In most studies, the patients undergoing surgery served as their own controls. Two studies also included control groups of healthy volunteers …”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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The influence of bariatric surgery on oral drug bioavailability in patients with obesity: A systematic review

et al. 2019

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Drug absorption in bariatric surgery patients: A narrative review

Alalwan

Friedman

Alfayez

et al. 2022

Health Science Reports

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Background: Despite the increase in the number of bariatric surgeries performed, little is known about the impact of the surgery on drug absorption. Unpredictability is assumed with drugs, given the anatomical changes after surgery.Objective: To evaluate the impact of bariatric surgery on drug absorption based on the type of procedure performed. Methods:We conducted a comprehensive literature review searching PubMed/ Medline for published studies (from inception to December 2017) that evaluate the use of drugs and the assessment of drug absorption after bariatric surgery.Pharmacokinetic/pharmacodynamic studies, case reports, and observational studies were included in our review. Results:We found 60 studies addressing drug use after bariatric surgery. Twentyeight studies reported a decrease in drug absorption after bariatric surgery while only four studies showed an increase in drug absorption. Unchanged absorption of drugs was seen in 23 studies after the surgery. Conclusion:The available information shows variations in drug absorption after bariatric surgery. The unpredictability may result from factors related to the patient, drug, and/or type of surgery. Therefore, pharmacists' involvement and close monitoring of patients after bariatric surgery could be effective to avoid sub-/ supratherapeutic responses.

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The Impact of Proximal Roux‐en‐Y Gastric Bypass Surgery on Acetaminophen Absorption and Metabolism

et al. 2020

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Background Roux‐en‐Y gastric bypass (RYGBS), a surgery that creates a smaller stomach pouch and reduces the length of small intestine, is one of the most common medical interventions for the treatment of obesity. Aim The aim of this study was to determine how RYGBS affects the absorption and metabolism of acetaminophen. Materials and Methods Ten morbidly obese patients received 1.5 g of liquid acetaminophen (APAP) orally on three separate pharmacokinetic study days (i.e., pre‐RYGBS baseline and 3 and 12 months post‐RYGBS). Plasma was collected at pre‐specified timepoints over 24 hours, and the samples were analyzed using liquid chromatography–mass spectrometry for APAP, APAPglucuronide (APAP‐gluc), APAP‐sulfate (APAP‐sulf), APAP‐cysteine (APAP‐cys), and APAP‐Nacetylcysteine (APAP‐nac). Result Following RYGBS, peak APAP concentrations at the 3‐month and 12‐month visits increased by 2.0‐fold compared to baseline (p=0.0039 and p=0.0078, respectively) and the median time to peak concentration decreased from 35 to 10 minutes. In contrast, peak concentrations of APAP‐gluc, APAP‐sulf, APAP‐cys, and APAP‐nac were unchanged following RYGBS. The apparent oral clearance of APAP and the ratios of metabolite area under the curve (AUC)‐to‐APAP AUC for all four metabolites decreased at 3 and 12 months post‐RYGBS compared to the presurgical baseline. In a simulation of expected steady‐state plasma concentrations following multiple dosing of 650 mg APAP every 4 hours, post‐RYGBS patients had higher steady‐state peak APAP concentrations compared to healthy individuals and obese pre‐RYGBS patients, though APAP exposure was unchanged compared to healthy individuals. Conclusion Following RYGBS, the rate and extent of APAP absorption increased and decreased formation of APAP metabolites was observed, possibly due to downregulation of Phase II and cytochrome P450 2E1 enzymes.

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Pharmacokinetics in Morbid Obesity: Influence of Two Bariatric Surgery Techniques on Paracetamol and Caffeine Metabolism

Abstract: Paracetamol pharmacokinetics and caffeine plasma levels are altered in severely obese patients. The two studied bariatric surgical techniques normalize paracetamol oral bioavailability without impairing the liver function (measured by cytochrome P450 1A2 activity).

Cited by 24 publications

References 23 publications

The influence of bariatric surgery on oral drug bioavailability in patients with obesity: A systematic review

The influence of bariatric surgery on oral drug bioavailability in patients with obesity: A systematic review

Drug absorption in bariatric surgery patients: A narrative review

The Impact of Proximal Roux‐en‐Y Gastric Bypass Surgery on Acetaminophen Absorption and Metabolism

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