Combining benefits of an adrenergic and a muscarinic blocker in a single formulation - a pharmacokinetic evaluation.
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 72 h 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.
Clinical Pharmacology and Pharmacokinetics, Ranbaxy Laboratories Limited, Plot No. GP-5, HSIDC, Old Delhi-Gurgaon Road, Gurgaon, Haryana 122015, India.
Shabana
S
Nazarudheen
Surajit
S
Dey
Kirti
K
Kandhwal
Rachna
R
Arora
Simrit
S
Reyar
Arshad H
AH
Khuroo
Tausif
T
Monif
Sumit
S
Madan
Vinod
V
Arora
D058668:Adrenergic alpha-1 Receptor Antagonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000328:Adult; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D004338:Drug Combinations; D006801:Humans; D008297:Male; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011799:Quinazolines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011812:Quinuclidines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000069464:Solifenacin Succinate; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency; D064804:Urological Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
D058668:Adrenergic alpha-1 Receptor Antagonists; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D018727:Muscarinic Antagonists; D011799:Quinazolines; D011812:Quinuclidines; D044005:Tetrahydroisoquinolines; D064804:Urological Agents; C047638:alfuzosin; D000069464:Solifenacin Succinate
90% Confidence interval; Alfuzosin; Bioequivalence; Fixed dose combination; Pharmacokinetic study; Solifenacin