title: Impact of Roux-en-Y Gastric Bypass Surgery on Pharmacokinetics of Administered Drugs: Implications and Perspectives.
abstract: Obesity epidemic has grown out of proportion with increased heath cost because of comorbidity associated with obesity. Due to mediocre benefit from pharmacological interventions, bariatric surgery popularly known as Roux-en-Y gastric bypass (RYGB) surgery has been increasingly practiced. Although RYGB significantly reduces body mass index, it also alters the local gut environment leading to significant changes in the drug absorption and bioavailability. The focus of the review is to present and critically evaluate case studies pertaining to pharmacokinetic data gathered till date on subjects after RYGB. A large portion of the reviewed examples showed reduced area under the concentration versus time curve [area under curve (AUC)] of drugs after RYGB (44%), whereas equal number of investigations showed increased (26%) or unaltered AUC (26%) after RYGB. There was one instance (4%), where the AUC was highly variable and individual subject dependent. Examination of drugs that showed reduced bioavailability suggested that a complex interplay of various factors such as solubility, permeability, metabolic enzymes, and transporters may have contributed for the observed effect. The increased bioavailability seemed to be related to permeability enhancement and generally in drug classes that have reduced metabolism. Based on the review, there is a significant risk of therapy failure for certain drugs because of subtherapeutic plasma levels. The need to readjust doses immediately after RYGB may be considered based on the therapeutic drug monitoring (TDM) findings. It seems prudent to initiate TDM for certain disease areas or drug classes until stable doses are established after RYGB through the appropriate pharmacokinetic and/or pharmacodynamics surrogate, as appropriate.
authors.affiliation: Dr Reddy's Institute of Life Sciences, Clinical Pharmacology and Biopharmaceutics, Gachibowli, Hyderabad, Telangana, India.
authors.forename: Nuggehally R
authors.initials: NR
authors.lastname: Srinivas
mesh_terms: D019540:Area Under Curve; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods; D015390:Gastric Bypass / Q000379:methods*; D006801:Humans; D009765:Obesity / Q000150:complications / Q000453:epidemiology / Q000601:surgery*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism; D010599:Pharmacokinetics
chemical_list: D004364:Pharmaceutical Preparations