Drug disposition before and after gastric bypass: fenofibrate and posaconazole

Gesquiere, Ina; Hens, Bart; Schueren, Bart Van der; Mols, Raf; Hoon, Jan de; Lannoo, Matthias; Matthys, Christophe; Foulon, Veerle; Augustijns, Patrick

doi:10.1111/bcp.13054

Cited by 27 publications

(31 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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%

“…To investigate the consequence of delayed contact with bile salts after surgery, fenofibrate can be used as a model drug because its solubility is highly dependent on bile salt concentrations, while posaconazole dissolution is pH dependent and can thus be used to indicate the effect of increased gastric pH following surgery . The results showed that the disposition of fenofibrate remained unaltered, whereas the exposure of posaconazole was reduced following surgery . A substrate less dependent on bile acids for its absorption would have been expected to show an increased absorption rate, but since the contact with bile acids is delayed after RYGBP, the accelerated gastric emptying time had a less visible effect on a substrate such as fenofibrate.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2019

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Of the total 21 studies, some conducted more than one procedure: 19 studies investigated RYGB, five investigated SG, two investigated BPD‐DS, and one study investigated mini‐GB . The number of participants in these studies ranged from five patients in a single study to a maximum of 34 patients.…”

Section: Resultsmentioning

confidence: 99%

“…The drugs investigated in this review were benzodiazepines: midazolam; anti‐arrhythmics: digoxin; corticosteroids: hydrocortisone; hormonal: desogestrel; antidepressants: venlafaxine, escitalopram, duloxetine, citalopram, and sertraline; antihypertensives: metoprolol; lipid‐reducing drugs: fenofibrate, and atorvastatin; anti‐infectives: posaconazole, amoxicillin, and linezolid; analgesics: morphine, and paracetamol; anticoagulant: rivaroxaban; and antiplatelet: aspirin; and acid‐reducing drugs: omeprazole . Amouyal et al included drugs for treatment of human immunodeficiency virus (HIV), namely, the combinations of the antiretroviral drugs: abacavir, atazanavir, efavirenz, emtricitabine, lamivudine, darunavir, raltegravir, ritonavir, and tenofovir …”

Section: Resultsmentioning

confidence: 99%

“…In the included articles, 11 studies reported a statistically significant change in pharmacokinetics before and after a bariatric procedure, measured as a change in either C max , T max , or AUC with statistical significance determined with a P value lower than .05. In six studies, the results were either reported as nonsignificant or the P values presented were above the threshold for statistical significance ( P < .05).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacokinetic changes post–bariatric surgery: A scoping review

McLachlan

Chaar

2020

Obesity Reviews

View full text Add to dashboard Cite

Summary Bariatric surgeries induce structural changes that can alter the absorption of drugs in patients already at risk of polypharmacy. This scoping review aimed to explore pharmacokinetic changes of orally administered drugs in patients post‐bariatric surgery, and assess the quality and level of bias. Electronic databases were searched for articles relating to bariatric surgery and pharmacokinetics published between 1998 and 2019. Pre‐post studies reporting on pharmacokinetic parameters were included, and the Newcastle‐Ottawa Scale was used to assess risk‐of‐bias. A total of 21 studies were included in this review, and changes in absorption were reported in all included studies across 29 drugs. In 11 studies, this change was reported as statistically significant (p<.05), while six reported a nonsignificant change. More drugs exhibited a shorter Tmax and higher Cmax after surgery than otherwise, however changes in AUC were variable. Four studies were assessed as having fair quality while the remainder of the included studies were of good quality and low risk‐of‐bias. Bariatric surgery alters the absorption of drugs and several mechanisms are implicated to be responsible. Short and long‐term monitoring is recommended in patients post‐surgery for clinical changes in response to medications. Future research with a higher number of participants and greater control of variables, such as concurrent medications, malabsorptive disorders, and body composition should be considered.

show abstract

Redefining Statin Dosage Post‐Gastric Bypass: Insights from a Population Pharmacokinetics–Pharmacodynamics Link Approach

Conchon Costa,

Medeiros,

Kang

et al. 2024

The Journal of Clinical Pharma

View full text Add to dashboard Cite

Roux‐en‐Y gastric bypass (RYGB) involves creating a small stomach pouch, bypassing part of the small intestine, and rerouting the digestive tract. These alterations can potentially change the drug exposure and response. Our primary aim was to assess the impact of RYGB on the pharmacokinetics of simvastatin lactone (SV) and its active metabolite, simvastatin hydroxy acid (SVA). Ultimately, we aimed to optimize dosing for this understudied population by employing a population pharmacokinetic–pharmacodynamic link approach. The study comprised patients who had undergone RYGB surgery and individuals without a previous history of RYGB. All participants received a single oral dose of simvastatin. Plasma concentration data were analyzed with a nonlinear mixed‐effect modeling approach. A parent–metabolite model with first‐order absorption, 2‐compartments for SV and 1‐compartment for SVA, linear elimination, and enterohepatic circulation best described the data. The model was linked to the turnover pharmacodynamic model to describe the SVA inhibition on LDL‐cholesterol production. Our simulations indicated that following RYGB surgery, the exposure to SV and SVA decreased by 40%. Consequently, for low‐intensity statin patients, we recommend increasing the dose from 10 to 20 mg in post‐RYGB patients to maintain a comparable response to that of non‐operated subjects. Moderate‐intensity statin patients should require increasing doses to 40 or 60 mg or the addition of a non‐statin medication to achieve similar therapeutic outcomes. In conclusion, individuals post‐RYGB exhibit diminished exposure to SV and may benefit from increasing the dose or adjunctive therapy with non‐statin drugs to attain equivalent responses and mitigate potential adverse events.

show abstract

Drug disposition before and after gastric bypass: fenofibrate and posaconazole

Abstract: The disposition of fenofibrate was not altered after RYGB, whereas the oral disposition of posaconazole was significantly decreased following RYGB.

Cited by 27 publications

References 33 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

Pharmacokinetic changes post–bariatric surgery: A scoping review

Redefining Statin Dosage Post‐Gastric Bypass: Insights from a Population Pharmacokinetics–Pharmacodynamics Link Approach

Contact Info

Product

Resources

About