Bioequivalence Study of Sodium Valproate and Valproic Acid Tablets

Bioavailability is the extent and rate to which the active drug ingredient or active moiety from the drug product is absorbed and becomes available at the site of drug action. Bioavailability of an active substance delivered from a pharmaceutical product should be known and reproducible. In the past, several therapeutic misadventures related to differences in bioavailability affirm to the necessity of testing the performance of dosage forms in delivering the active substance to the systemic circulation and thereby to the site of action. If there is no clinically significant difference in the bioavailability of two medicines they are considered to be bioequivalent.The bioavailability and bioequivalence studies of various drug candidates have been routine regulatory requirements in many countries for licensing of the drug product. Department of Drug Administration, Ministry of health and Population has encouraged Nepalese Pharmaceutical Industries legally to submit pharmacokinetic data where possible for licensing purpose for certain drug candidates and their dosage forms. The comparative in-vivo bioequivalence study is necessary for those products which have low therapeutic index, low bioavailability, non-linear kinetics, poor dissolution profile, variable bioavailability and/or bioequivalence. Department of Drug Administration necessitated bioequivalence and bioavailability study for the modified release dosage form of those drug molecules whose blood steady state concentration is of great importance, e.g. sodium valproate, valproic acid, carbamazepine, antibiotics etc. Considering the need to confirm safety and effectiveness of the medications and also for the regulatory requirement, this study to assess the bioequivalence of sodium valproate and valproic acid extended release tablet manufactured by a Nepalese pharmaceutical company, Asian Pharmaceuticals Pvt. Ltd., with an innovator formulation is being carried out in healthy human volunteers.

Inclusion Criteria:Age: 18 - 60 years.Gender: Male / female or bothWeight: At least 50 kg (110 lbs) and within 15% of Ideal Body Weight (IBW). BMI between 18.0 and 29.9 kg/m², inclusiveAll subjects should be judged normal and healthy during a pre-study medical evaluation (physical examination, including vital signs, laboratory evaluations, 12-lead ECG, hepatitis B, hepatitis C and HIV tests) performed within 14 days of the initial dose of study medication.Consent: Demonstrates understanding of the study and willingness to participate as evidenced by voluntary written informed consent (signed and dated) obtainedExclusion Criteria:Social Habits:i. Use of any tobacco products within month of the start of the study. ii. Ingestion of any alcoholic, caffeine- or xanthine-containing food or beverage within 48 hours prior to the initial dose of study medication.iii. Ingestion of any vitamins or herbal products within 7 days prior to the initial dose of the study medication.iv. Any recent, significant change in dietary or exercise habits. v. History of drug and/or alcohol abuse.Medications:i. Use of any prescription or over-the-counter (OTC) medications within 14 days prior to the initial dose of study medication.ii. Use of any medication known to alter hepatic enzyme activity within 28 days prior to the initial dose of study medication.Diseases:i. History of any significant cardiovascular, hepatic, renal, pulmonary, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic disease.ii. Acute illness at the time of either the pre-study medical evaluation or dosing.iii. A positive HIV, hepatitis B, or hepatitis C tests.Abnormal and clinically significant laboratory test results:i. Clinically significant deviation from the Guide to Clinically Relevant Abnormalities.ii. Abnormal and clinically relevant ECG tracing.Clinical Studies i. Participation in any clinical study (inclusive of final post-study examination) within the 12 weeks before screening visit.ii. Subject whose participation in this study will result in a participation in more than four studies over a twelve month period.Donation or loss of a significant volume of blood or plasma (> 450 mL) within 28 days prior to the initial dose of study medication.Subjects who have received an investigational drug within 30 days prior to the initial dose of study medication.Allergy or hypersensitivity to valproic acid / sodium valproate or any other related products.History of difficulties in swallowing, or any gastrointestinal disease which could affect the drug absorption.Consumption of grapefruit or grapefruit containing products within 7 days of drug administration.