title: Bioequivalence of two lansoprazole delayed release capsules 30 mg in healthy male volunteers under fasting, fed and fasting-applesauce conditions: a partial replicate crossover study design to estimate the pharmacokinetics of highly variable drugs.
abstract: An open-label, 2-treatment, 3-sequence, 3-period, single-dose, partial replicate crossover studies under fasting (n=48), fed (n=60) and fasting-applesauce (n=48) (sprinkled on one table spoonful of applesauce) modalities were conducted in healthy adult male volunteers to evaluate bioequivalence between 2 formulations of lansoprazole delayed release capsules 30 mg. In all the 3 studies, as per randomization, either test or reference formulations were administered in a crossover manner with a required washout period of at least 7 days. Blood samples were collected adequately (0-24 h) to determine lansoprazole plasma concentrations using a validated LC-MS/MS analytical method. To characterize the pharmacokinetic parameters (Cmax, AUC0-t, AUC0-∞, Tmax, Kel and T1/2) of lansoprazole, non-compartmental analysis and ANOVA was applied on ln-transformed values. The bioequivalence was tested based on within-subject variability of the reference formulation. In fasting and fed studies (within-subject variability>30%) bioequivalence was evaluated with scaled average bioequivalence, hence for the pharmacokinetic parameters Cmax, AUC0-t and AUC0-∞, the 95% upper confidence bound for (μT-μR)2-θσ2 WR was ≤0, and the point estimates (test-to-reference ratio) were within the regulatory acceptance limit 80.00-125.00%. In fasting-applesauce study (within-subject variability<30%) bioequivalence was evaluated with average bioequivalence, the 90% CI of ln-transformed data of Cmax, AUC0-t and AUC0-∞ were within the regulatory acceptance limit 80.00-125.00%. Based on these aforesaid statistical inferences, it was concluded that the test formulation is bioequivalent to reference formulation.
authors.affiliation: Clinical Pharmacology and Pharmacokinetics, Integrated Product Development, Dr.Reddy's Laboratories Limited, Hyderabad, India.
authors.forename: S
authors.initials: S
authors.lastname: Thota
authors.forename: S M
authors.initials: SM
authors.lastname: Khan
authors.forename: S K
authors.initials: SK
authors.lastname: Tippabhotla
authors.forename: R
authors.initials: R
authors.lastname: Battula
authors.forename: C
authors.initials: C
authors.lastname: Gadiko
authors.forename: V
authors.initials: V
authors.lastname: Vobalaboina
mesh_terms: D000293:Adolescent; D000328:Adult; D002214:Capsules; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004435:Eating; D005215:Fasting; D006801:Humans; D064747:Lansoprazole / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency
chemical_list: D002214:Capsules; D003692:Delayed-Action Preparations; D054328:Proton Pump Inhibitors; D064747:Lansoprazole