Pharmacokinetic changes and approach to drug dosing in patients with obesity and after bariatric surgery

INTRODUCTION: Obesity is a chronic disease associated with multiple comorbidities and can affect drug pharmacokinetics. Appropriate dosing in obese patients is essential to ensure therapeutic efficacy and safety. OBJECTIVE: To summarize the impact of obesity and bariatric surgery on drug pharmacokinetics and provide recommendations for individualized dosing. METHODS: Review of available literature and clinical guidelines addressing changes in drug absorption, distribution, metabo-lism, and excretion in obese patients and after bariatric procedures. RESULTS: Obesity is associated with nonlinear changes in volume of distribution and heterogenous changes in clearance: modification of certain CYP enzyme activity (notably CYP3A4, CYP2C19, CYP2E1), and alteration of renal function. Anatomical and functional chages of gastrointestinal tract (GIT) following bariatric surgery variably modify absorption area, pH, GIT motility and lead to improvement in metabolic comorbidities. Dose adjustments are particularly important for drugs with a narrow therapeutic range, weight-based dosing regimens, and highly lipophilic substances. An individualized approach and therapeutic drug monitoring are recommended in clinical practice. CONCLUSION: Universal drug dosing regimens for obese patients or those after bariatric surgery are unavailable for most drugs. Body composition and other patient-specific factors, as well as drug pharmacokinetics should be considered. Clinical pharmacists can contribute to optimal pharmacotherapy in this heterogeneous population.