title: Bioequivalence of fixed dose combination of atorvastatin 10 mg and aspirin 150 mg capsules: a randomized, open-label, single-dose, two-way crossover study in healthy human subjects.
abstract: The present study evaluated the bioavailability and bioequivalence of fixed dose combination test formulation (atorvastatin 10 mg and aspirin 150 mg capsule) against marketed reference formulations (Lipitor® tablets 10 mg and Nu-Seals tablets 75 mg). This study was an open label, balanced, randomized, 2-treatment, 2-period, 2-sequence, single dose, crossover trial in 80 healthy adult human volunteers under fasting conditions. Plasma concentrations of atorvastatin, aspirin and salicylic acid were quantified using LC-MS/MS method. Pharmacokinetic parameters were estimated by noncompartmental model and mean pharmacokinetic parameters were comparable between test and reference formulations. The mean pharmacokinetic parameters (AUC0-t, AUC0-∞, Cmax, Cmax /AUC0-t and Cmax/AUC0-∞) for atorvastatin test and reference formulations were (52.69 ng.h/mL, 55.64 ng.h/mL, 9.45 ng/mL, 0.18 1/h and 0.17 1/h) and (52.20 ng.h/mL, 55.38 ng.h/mL, 10.25 ng/mL, 0.20 1/h and 0.19 1/h) respectively; and for aspirin were (1 378.62 ng.h/mL, 1 383.90 ng.h/mL, 1 022.18 ng/mL, 0.75 1/h and 0.75 1/h) and (1 314.17 ng.h/mL, 1 314.50 ng.h/mL, 985.90 ng/mL, 0.75 1/h and 0.75 1/h) respectively. Where as for salicylic acid, above parameters were (42 357.57 ng.h/mL, 44 139.47 ng.h/mL, 9 820.15 ng/mL, 0.24 1/h and 0.23 1/h) and (40 217.08 ng.h/mL, 42 032.44 ng.h/mL, 9 569.18 ng/mL, 0.24 1/h and 0.24 1/h) respectively for test and reference formulations. The 90% confidence intervals of atorvastatin and salicylic acid for AUC0-t, AUC0-∞, Cmax, Cmax /AUC0-t and Cmax/AUC0-∞ parameters were found to be within the acceptable regulatory bioequivalence limits. In conclusion, the new fixed dose combination test formulation was bioequivalent to the reference formulations under fasting conditions.
authors.affiliation: Clinical Pharmacology and Pharmacokinetics, IPDO, Dr. Reddy's Laboratories Limited, Hyderabad, India. sudhakarkt@drreddys.com
authors.forename: S K
authors.initials: SK
authors.lastname: Tippabhotla
authors.forename: M R
authors.initials: MR
authors.lastname: Betha
authors.forename: C
authors.initials: C
authors.lastname: Gadiko
authors.forename: R
authors.initials: R
authors.lastname: Battula
authors.forename: M
authors.initials: M
authors.lastname: Nakkawar
authors.forename: R
authors.initials: R
authors.lastname: Cheerla
authors.forename: S M
authors.initials: SM
authors.lastname: Khan
authors.forename: S
authors.initials: S
authors.lastname: Yergude
authors.forename: S
authors.initials: S
authors.lastname: Thota
authors.forename: V
authors.initials: V
authors.lastname: Vobalaboina
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001241:Aspirin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000069059:Atorvastatin; D002214:Capsules; D018592:Cross-Over Studies; D004338:Drug Combinations; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics*; D008297:Male; D011758:Pyrroles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency
chemical_list: D002214:Capsules; D004338:Drug Combinations; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; D001241:Aspirin