Comparison of the Pharmacokinetics of Two Generic Antidepressants and Their Respective Brand Preparations

Study Overview
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Brief Summary
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Generic medications should be the equivalent of brand medications with the exception of their price. Before a generic medication is introduced, its bioequivalence within a window of 80 to 125% of the original has to be demonstrated. There are reports that this criterion is not always followed in post-marketed periods. Such investigations were triggered by the observation that some patients previously stable on original medications relapsed when switched to a presumable equivalent generic. Several factors could account for this problem. Given reports of such problems occurring with the antidepressants citalopram and venlafaxine, some pharmacokinetic properties of specific brands of generics and the originals will be examined for these two medications. Twelve healthy male volunteers will participate in this crossover study. It is anticipated that there will be significant differences emerging between the two formulations given the clinical reports of patients deteriorating when switched from the original to the generic preparations.

Official Title
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Examination of the Pharmacokinetic Properties of Two Generic Antidepressants and Their Respective Brand Preparations in Healthy Male Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: Venlafaxine
* Drug: Gen-Citalopram
* Drug: Effexor XR
* Drug: Celexa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteers (absence of diseases: psychiatric, physical, neurological, metabolic,...) Exclusion Criteria: Psychiatric disorder Hepatic disease Renal disease Gastrointestinal disease Hematological disease Smokers Physical and/or neurological disease Positive urine drug screen Abnormal blood pressure Abnormal urine/blood analysis (sodium, potassium, chloride, creatinine, urea, ALT, AST, total protein, glucose, and TSH)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Crossover Effexor / NOVO-Venlafaxine Examination of the bioequivalence of Effexor (Wyeth Pharmaceuticals) and NOVO-Venlafaxine (NOVOPHARM). Both drugs will be given at the dose of 75 mg/day (one capsule per day) for 4 consecutive days. A washout period (corresponding to 10 half-life of the active metabolite desmethylvenlafaxine) will be respected after receiving each medication. | Drug: Venlafaxine<br>* NOVO-Venlafaxine XR 75 mg (NOVOPHARM, Generic)<br>Drug: Effexor XR<br>* Effexor XR 75 mg (Wyeth Pharmaceuticals, Brand Name)<br>|
| Active Comparator: 2<br>Crossover Celexa/Gen-citalopram Examination of the bioequivalence of Celexa (Lundbeck, Brand Name) and Gen-Citalopram (Genpharm, Generic). Both drugs will be given at the dose of 40 mg/day (one tablet per day) for 8 consecutive days. A washout period (corresponding to 10 half-life of citalopram) will be respected after receiving each medication. | Drug: Gen-Citalopram<br>* Gen-Citalopram 40 mg (Genpharm, Generic)<br>Drug: Celexa<br>* Celexa 40 mg (Lundbeck, Brand Name)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood levels of drugs and their metabolite (when appropriate) will be evaluated for both the generic and the brand name medication. |  | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Therapeutic Equivalency, Human Experimentation, Bioequivalence, Brand name, Generic, Antidepressant, Healthy volunteers