Oral drug dosing following bariatric surgery: General concepts and specific dosing advice

Kingma, Jurjen S; Burgers, Desiree M. T.; Monpellier, Valerie M.; Wiezer, Marinus J.; Oud-Alblas, Heleen J. Blussé van; Vaughns, Janelle D.; Sherwin, Catherine M.T.; Knibbe, Catherijne A. J.

doi:10.1111/bcp.14913

Cited by 33 publications

(19 citation statements)

References 144 publications

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“…Therapeutic drug monitoring protocols and validated methods are available for individualised treatment. However, predicting pharmacokinetics based on drug properties proved to be challenging owing to the complexity of BS and individual drug properties [ 98 ]. Monitoring ARV exposure and activity is crucial in this population.…”

Section: Successful Arv Candidates Post-bsmentioning

confidence: 99%

Implications of Bariatric Surgery on the Pharmacokinetics of Antiretrovirals in People Living with HIV

et al. 2022

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Bariatric surgery is increasingly applied among people living with HIV to reduce obesity and the associated morbidity and mortality. In people living with HIV, sufficient antiretroviral exposure and activity should always be maintained to prevent development of resistance and disease progression. However, bariatric surgery procedures bring various gastrointestinal modifications including changes in gastric volume, and acidity, gastrointestinal emptying time, enterohepatic circulation and delayed entry of bile acids. These alterations may affect many aspects of antiretroviral pharmacokinetics. Some drug characteristics may result in subtherapeutic exposure and the potential related risk of treatment failure and resistance. Antiretrovirals that require low pH, administration of fatty meals, longer intestinal exposure, and an enterohepatic recirculation for their absorption may be most impacted by bariatric surgery procedures. Additionally, some antiretrovirals can interact with the polyvalent cations in supplements or drugs inhibiting gastric acid, thereby preventing their use as these comedications are commonly prescribed post-bariatric surgery. Predicting pharmacokinetics on the basis of drug characteristics solely proved to be challenging, therefore pharmacokinetic studies remain crucial in this population. Here, we discuss general implications of bariatric surgery on antiretroviral outcomes in people living with HIV as well as drug properties that are relevant for the choice of antiretroviral treatment in this special patient population. Additionally, we summarise studies that evaluated the pharmacokinetics of antiretrovirals post-bariatric surgery. Finally, we performed a comprehensive analysis of theoretical considerations and published pharmacokinetic and pharmacodynamic data to provide recommendations on antiretrovirals for people living with HIV undergoing bariatric surgery.

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Section: Successful Arv Candidates Post-bsmentioning

confidence: 99%

Implications of Bariatric Surgery on the Pharmacokinetics of Antiretrovirals in People Living with HIV

et al. 2022

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“…Notably, the relationship between the time to reach peak concentration (T max ) and C max are well described in previous literature. McLachlan et al [ 9 ] discussed that the change in transit time through the stomach and weight loss with consequent changes in body composition can contribute to the decrease in T max accompanied by an increase in the C max after bariatric surgery, and similar comments were also found in another review article [ 26 ]. Meanwhile, C max is an observed value and is largely dependent on the sampling time.…”

Section: Discussionmentioning

confidence: 74%

“…Obviously, weight loss is observed after bariatric surgery. However, there are other factors affecting the ADME of a particular drug and thus, a drug-by-drug risk assessment was recommended in a recent article [ 26 ]. Reviewing previous literature, we determined that the design of the clinical studies was heterogeneous and wondered if the clinical design could have affected the evaluation of the changes for the PK characteristics.…”

Section: Discussionmentioning

confidence: 99%

Considerations for clinical evaluation of the effects of bariatric surgery on the pharmacokinetics of orally administered drugs

Bae

Song

et al. 2022

Transl Clin Pharmacol

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Obesity has been a growing worldwide concern, and surgical intervention including bariatric surgery is considered as one of the options for treatment. However, there still is controversy over the change in pharmacokinetics (PKs) of drugs after the surgery. To investigate the potential covariates that can influence the area under the curve (AUC) and maximum plasma concentration (C max ), the design of previous studies was reviewed based on pre-determined eligibility criteria. Each study calculated the ratios of the AUC and C max before and after bariatric surgery. These studies investigated whether the PK parameters were affected by the time after the surgery or by the type of control group. The ratio of the AUC calculated in the early and late follow-up period was similar across Roux-en Y gastric bypass patients. No significant difference in the PK parameters was found between the pre-surgical patients and matched healthy subjects. However, certain control groups could be preferable depending on the purpose of the clinical trial. Although C max was inconsistent compared to the AUC, insufficient sampling of the time points may have caused such an inconsistency. This is the first article exploring the appropriate methodology in designing clinical studies for changes in the PK characteristics of orally administered drugs in patients with bariatric surgery.

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“…The mechanisms by which bariatric surgery may influence drug absorption and pharmacokinetics are many and varied and relate to virtually all of the different ADME steps. ,, While solubility/dissolution is the first, essential, prerequisite step in the cascade of drug absorption, no single mechanism can predict the overall effects of the surgery on drug exposure and effect, , when increased, , decreased, or unchanged drug levels are all possible. A pre- versus post-surgery pharmacokinetics study can give the ultimate answer to this question; however, these studies are time- and effort-consuming, and the drugs that have to be investigated for their performance in bariatric patients are numerous.…”

Section: Discussionmentioning

confidence: 99%

Antiallergic Treatment of Bariatric Patients: Potentially Hampered Solubility/Dissolution and Bioavailability of Loratadine, but Not Desloratadine, Post-Bariatric Surgery

et al. 2022

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Gastrointestinal anatomical/physiological changes after bariatric surgery influence variables affecting the fate of drugs after ingestion, and medication management of these patients requires a thorough and complex mechanistic analysis. The aim of this research was to study whether loratadine/desloratadine antiallergic treatment of bariatric patients is at risk of being ineffective due to impaired solubility/dissolution. The pH-dependent solubility of loratadine/desloratadine was studied in vitro, as well as ex vivo, in gastric content aspirated from patients before versus after bariatric surgery. Then, a biorelevant dissolution method was developed to simulate the gastric conditions after sleeve gastrectomy (SG) or one-anastomosis gastric bypass (OAGB), accounting for key variables (intragastric volume, pH, and contractility), and the dissolution of loratadine/desloratadine was studied pre- versus post-surgery. Dissolution was also studied after tablet crushing or syrup ingestion, as these actions are recommended after bariatric surgery. Finally, these experimental data were implemented in a newly developed physiologically based pharmacokinetic (PBPK) model to simulate loratadine/desloratadine PK profiles pre- versus post-surgery. For both drugs, pH-dependent solubility was demonstrated, with decreased solubility at higher pH; over the pH range 1–7, loratadine solubility decreased ∼2000-fold, and desloratadine decreased ∼120-fold. Ex vivo solubility in aspirated human gastric fluid pre- versus post-surgery was in good agreement with these in vitro results and revealed that while desloratadine solubility still allows complete dissolution post-surgery, loratadine solubility post-surgery is much lower than the threshold required for the complete dissolution of the drug dose. Indeed, severely hampered loratadine dissolution was revealed, dropping from 100% pre-surgery to only 3 and 1% post-SG and post-OAGB, respectively. Tablet crushing did not increase loratadine dissolution in any post-bariatric condition, nor did loratadine syrup in post-OAGB (pH 7) media, while in post-laparoscopic SG conditions (pH 5), the syrup provided partial improvement of up to 40% dissolution. Desloratadine exhibited quick and complete dissolution across all pre-/post-surgery conditions. PBPK simulations revealed pronounced impaired absorption of loratadine post-surgery, with 84–88% decreased C max, 28–36% decreased F a, and 24–31% decreased overall bioavailability, depending on the type of bariatric procedure. Desloratadine absorption remained unchanged post-surgery. We propose that desloratadine should be preferred over loratadine in bariatric patients, and as loratadine is an over-the-counter medication, antiallergic therapy after bariatric surgery requires special attention by patients and clinicians alike. This mechanistic approach that reveals potential post-surgery complexity, and at the same time provides adequate substitutions, may contribute to better pharmacotherapy and overall patient care after bariatric surgery.

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Oral drug dosing following bariatric surgery: General concepts and specific dosing advice

Cited by 33 publications

References 144 publications

Implications of Bariatric Surgery on the Pharmacokinetics of Antiretrovirals in People Living with HIV

Implications of Bariatric Surgery on the Pharmacokinetics of Antiretrovirals in People Living with HIV

Considerations for clinical evaluation of the effects of bariatric surgery on the pharmacokinetics of orally administered drugs

Antiallergic Treatment of Bariatric Patients: Potentially Hampered Solubility/Dissolution and Bioavailability of Loratadine, but Not Desloratadine, Post-Bariatric Surgery

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