Friday , 12 July 2024

Bioequivalence Comparison between two Different Formulations of Alverine Citrate 120mg Capsules: An Open Label, Balanced, Randomized-Sequence, Single-Dose, Two-Period Crossover Study in Healthy Male Volunteers

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.

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.

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