Trends in oral drug bioavailability following bariatric surgery: examining the variable extent of impact on exposure of different drug classes

Abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Changes to oral drug bioavailability have been observed post bariatric surgery. However, the magnitude and the direction of changes have not been assessed systematically to provide insights into the parameters governing the observed trends. Understanding these can help with dose adjustments. WHAT THIS STUDY ADDS • Analysis of drug characteristics based on a biopharmaceutical classification system is not adequate to explain observed trends in altered oral drug bioavailability following bariatric surgery, although the findings suggest solubility to play an important role. AIMS To identify the most commonly prescribed drugs in a bariatric surgery population and to assess existing evidence regarding trends in oral drug bioavailability post bariatric surgery. METHODS A retrospective audit was undertaken to document commonly prescribed drugs amongst patients undergoing bariatric surgery in an NHS hospital in the UK and to assess practice for drug administration following bariatric surgery. The available literature was examined for trends relating to drug permeability and solubility with regards to the Biopharmaceutics Classification System (BCS) and main route of elimination. RESULTS No significant difference in the ‘post/pre surgery oral drug exposure ratio’ (ppR) was apparent between BCS class I to IV drugs, with regards to dose number (Do) or main route of elimination. Drugs classified as ‘solubility limited’ displayed an overall reduction as compared with ‘freely soluble’ compounds, as well as an unaltered and increased ppR. CONCLUSION Clinical studies establishing guidelines for commonly prescribed drugs, and the monitoring of drugs exhibiting a narrow therapeutic window or without a readily assessed clinical endpoint, are warranted. Using mechanistically based pharmacokinetic modelling for simulating the multivariate nature of changes in drug exposure may serve as a useful tool in the further understanding of postoperative trends in oral drug exposure and in developing practical clinical guidance.

A mechanistic pharmacokinetic model to assess modified oral drug bioavailability post bariatric surgery in morbidly obese patients: interplay between CYP3A gut wall metabolism, permeability and dissolution

“…The selected drugs (simvastatin, omeprazole, diclofenac, fluconazole and ciprofloxacin) had a wide range of physicochemical and metabolic attributes and were commonly used in patients undergoing bariatric surgery [12] . Oral drug exposure was simulated for a low, medium and high therapeutic dose in accordance with the British National Formulary, which included: simvastatin immediate release (10, 20 and 80 mg), diclofenac enteric coated (25, 50 and 75 mg), omeprazole enteric coated (10, 20 and 40 mg), fluconazole immediate release (50, 200, 400 mg) and ciprofloxacin immediate release (250, 500 and 750 mg).…”

“…Different types of bariatric surgery will impose a number of physiological changes varying in extent depending on the invasiveness of the procedure. Many of these alterations are known to affect the bioavailability of orally administered drugs, although studies investigating alterations in oral drug exposure pre‐ to postoperatively have been limited [12] …”

“…Due to the multifactorial physiological implications of bariatric surgery, attempts to explain trends in changes to oral bioavailability following bariatric surgery using single attributes of drugs or simplified categorisations such as the biopharmaceutics classification system (BCS) have been unsuccessful [12] …”

Oral Anticoagulant Use After Bariatric Surgery: A Literature Review and Clinical Guidance

“…SG and AGB are solely restrictive. In SG, a longitudinal resection of the stomach reduces its volume to approximately 60–80 mL, thereby restricting caloric intake 4, 5 . In AGB, an adjustable silicone band is placed around the stomach to create a smaller pouch that similarly restricts caloric intake.…”

“…Indeed, a study found that using PK parameters within a biopharmaceutical classification system could not alone explain the observed variability in bioavailability after bariatric surgery 4 . Therefore, the sum of the changes imparted by bariatric procedures makes it difficult, if not impossible, to accurately predict oral bioavailability – and, consequently, PK, clinical efficacy and safety – for a given drug without a dedicated study of that drug 2, 28 .…”