Combining benefits of an adrenergic and a muscarinic blocker in a single formulation – A pharmacokinetic evaluation

• Published in: Regulatory toxicology and pharmacology 2013-11, Vol.67 (2), p.226-231
• Main Authors: Nazarudheen, Shabana, Dey, Surajit, Kandhwal, Kirti, Arora, Rachna, Reyar, Simrit, Khuroo, Arshad H., Monif, Tausif, Madan, Sumit, Arora, Vinod
• Format: Article
• Language: English
• Subjects: 90% Confidence interval; Adrenergic alpha-1 Receptor Antagonists - administration & dosage; Adrenergic alpha-1 Receptor Antagonists - blood; Adrenergic alpha-1 Receptor Antagonists - pharmacokinetics; Adult; Alfuzosin; Bioequivalence; Cross-Over Studies; Delayed-Action Preparations - administration & dosage; Delayed-Action Preparations - pharmacokinetics; Drug Combinations; Fixed dose combination; Humans; Male; Muscarinic Antagonists - administration & dosage; Muscarinic Antagonists - blood; Muscarinic Antagonists - pharmacokinetics; Pharmacokinetic study; Quinazolines - administration & dosage; Quinazolines - blood; Quinazolines - pharmacokinetics; Quinuclidines - administration & dosage; Quinuclidines - blood; Quinuclidines - pharmacokinetics; Solifenacin; Solifenacin Succinate; Tetrahydroisoquinolines - administration & dosage; Tetrahydroisoquinolines - blood; Tetrahydroisoquinolines - pharmacokinetics; Therapeutic Equivalency; Urological Agents - administration & dosage; Urological Agents - blood; Urological Agents - pharmacokinetics; Young Adult
• ISSN: 0273-2300; 1096-0295
• DOI: 10.1016/j.yrtph.2013.07.015

•A fixed dose combination (FDC) of Alfuzosin and Solifenacin has been developed.•This new formulation is developed for LUTS/BPH alongside overactive bladder.•PK parameters of the FDC were compared with reference products in healthy subjects.•FDC was proved to be therapeutically equivalent to the individual formulations.•This FDC can be used in patient population safely and effectively. A pharmacokinetic bioequivalence study was conducted in Asian subjects, to compare a fixed dose combination capsule single oral dose of alpha adrenoceptor blocker—Alfuzosin hydrochloride 10mg extended release and muscarinic antagonists—Solifenacin succinate 5mg against individually administered Xatral XL 10mg tablets (Alfuzosin) of Sanofi Synthelabo Limited, United Kingdom (UK) and Vesicare 5mg tablets (Solifenacin) of Astellas Pharma Limited, UK under fed conditions. Blood samples were collected pre-dose up to 72h post dose for determination of plasma Alfuzosin and Solifenacin concentrations and calculation of the pharmacokinetic parameters. ANOVA was performed on the log (natural)-transformed pharmacokinetic parameters. A 90% confidence interval for the ratios of the test and reference product averages (least square means) were calculated for alfuzosin and solifenacin. The 90% confidence intervals obtained for alfuzosin for Cmax, AUC0−t and AUC0−∞ were 102.74–122.75%, 95.84–116.96% and 95.82–116.76%, respectively. The 90% confidence intervals obtained for Solifenacin for Cmax, and AUC0−72 were 89.55–97.91% and 90.47–99.38%, respectively. Based on the results, the fixed dose combination was concluded to be bioequivalent to individually administered products.