A Comparative Analysis of the Pharmacodynamic and Pharmacokinetic Properties of 2 Controlled‐Release Formulations Versus a Marketed Orlistat Product

A new modified-release oral formulation combines acarbose and orlistat (MR-OA) to enhance efficacy and reduce adverse effects through controlled drug release. This study aims to compare the pharmacodynamic properties of the orlistat component of MR-OA (MR-O) with a conventional orlistat product, Xenical (Conv-O), analyzing the percentage of fecal fat excretion. In addition, the pharmacokinetic properties of the complete formulation, MR-OA, were compared with Conv-O. In Part I of the study, 20 healthy volunteers were randomized in a single-blind, crossover trial to take MR-O or Conv-O (120-mg orlistat) 3 times daily for 9 days. Fecal fat was measured at baseline and after each treatment. MR-O and Conv-O similarly increased fecal fat percentage from 3.8% to 13.5%, confirming pharmacodynamic equivalence. Adverse events were few and generally rated as mild. In Part II, participants received MR-OA and then Conv-O, with blood samples collected for 12 hours to measure orlistat and acarbose levels. Orlistat's peak concentration stayed below 5 ng/mL, and acarbose plasma levels were mostly undetectable, indicating minimal systemic absorption. This shows that the new weight loss product MR-OA retains the dietary energy loss pathway used in Conv-O. Consistent with previous studies, minimal systemic absorption of orlistat and acarbose was observed for MR-OA, confirming that no significant alteration of the original substances occurs when modifying their release.