Obesity influences propranolol pharmacokinetics in patients undergoing coronary artery bypass grafting employing cardiopulmonary bypass

Abstract

Propranolol plasma levels and kinetic disposition may be altered by hypothermic cardiopulmonary bypass (CPB-H). We investigated the potential influence of obesity on propranolol pharmacokinetics in patients undergoing coronary artery bypass grafting employing CPB-H. Fifteen patients, receiving propranolol perorally pre- (10-40 mg, 2-3 times a day) and post-operatively (10 mg, once a day) were distributed in two groups, based on body mass index (BMI), in obese (n = 9, BMI: mean 29.4 kg/m²) and non-obese (n=6, BMI: mean 24.8 kg/m²). A serial of blood samples was collected at the pre- and post-operative periods at time dosing interval (Ä); propranolol plasma levels were measured one day before and after surgery using a high performance liquid chromatographic procedure described previously. PK Solutions software 2.0 was applied to obtain pharmacokinetic parameters. No changes on kinetic parameters as biological half-life (t1/2, p = 0.0625, NS), volume of distribution (Vd/F, p=0.8438, NS) and plasma clearance (CL T/F, p = 0.1563, NS) were obtained for the non-obese patients, while a prolongation of t1/2 (3.2 to 11.2 h, p< 0.0039), an increase on Vd/F (3.0 to 7.7 L/kg, p<0.0039) and reduction on CL T/F (11.3 to 9.2 mL/min.kg, p<0.0391) were obtained in the post-operative period for obese patients. Pharmacokinetic data could justify propranolol plasma concentrations in obese patients higher than in non-obeses, after surgery.