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I. Sarath Chandiran*1, Raghunadha Reddy Seelam2, Seelam Sai Satyanaraya Reddy3,
Ravindra Reddy S3
1Professor, Ratnam Institute of Pharmacy, Pidathapolur, SPSR Nellore-524346, Andhra Pradesh, India
2Department of Pharmaceutical Science, School of Pharmacy, University of Maryland, Pine Street, Baltimore, Maryland 21201, USA.
3Vardhaman College of Engineering, Hyderabad, Telangana, India.
A B S T R A C T
This present bioequivalence study was designed to determine the pharmacokinetic, bioavailability and bioequivalence of alverine citrate 120 mg capsules in comparison with Spasmonal Forte® 120 mg capsules after single dose administration under fasting conditions in healthy adult male subjects. An open-labeled, balanced, single-dose, 2-treatment, 2-period, 2-sequence, randomized crossover study was conducted in 12 healthy male volunteers. Each volunteer received a 120 mg capsule of the reference (or) test drug respectively. On the day of dosing, blood samples were collected before dosing & at various time points up to 4 days after dosing. Analysis of alverine and its metabolite 4-hydroxy alverine concentrations was performed using a validated LC-MS/MS method. The pharmacokinetic parameters were analyzed using the non-compartmental model. Drug safety and tolerability were assessed. The primary pharmacokinetic parameters at 90% CI were within the 80 to 125% interval required for bioequivalence as stipulated in the current regulations of the EU acceptance criteria. The geometric mean ratios (Test/Reference) between the two products of alverine capsule under fasting condition were 111.15% (98.67%-122.4%) and 113.41% (94.68%-118.74%) for Cmax ratios, 112.72% (91.12-114.35%) and 104.54% (94.73%-103.85%) for AUC0-t ratios and 103.73% (94.45%-111.5%) and 104.56% (103.24%-107.58%) for AUC0-inf ratios of aiverine and its metabolite respectively. 12 volunteers had completed both treatments. There was no significant difference of the Tmax parameter between the two formulations (p >0.05). No serious adverse events related to the study drugs were found. This single dose study found that the test formulation alverine citrate capsules is bioequivalent to the reference formulation Spasmonal Forte® capsules the extent and the rate of absorption, of 120 mg under fasting condition in healthy adult male volunteers according to the EU regulatory guidance.
Keywords: Alverine, 4-Hydroxy Alverine, Bioavailability, Bioequivalence, Intrasubject Variability.
