A Comparative Pharmacokinetic and Pharmacodynamic Study of Sildenafil in Adult Smokers and Non Smokers

Study Overview
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Brief Summary
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Smokers are at higher risk of developing Erectile dysfunction (ED) independent of age and comorbidities. Sildenafil is a cytochrome p3A4 (CYP3A4) substrate used for enhancing the erectile function in males. The study purpose is to determine the effect of smoking on male sexual function based on the international index of erectile function score (IIEF) and investigate the effect of smoking (Cigarettes or marijuana) on the pharmacokinetics and pharmacodynamics of sildenafil.

Detailed Description
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The study is a randomized, single dose, one way, open label, parallel study in thirty-six (36) subjects randomized into three groups;group(1) included twelve(12) healthy non-smoker males, group(2) included twelve(12) healthy smokers (Cigarettes) and group(3) included twelve(12) healthy smokers (marijuana). Each group received a single dose of Viagra 50 mg film coated tablet (Sildenafil 50 mg) Blood samples were collected at the following sampling intervals: pre-dose administration, 10 minutes, 20 minutes, 30 minutes, 45 minutes, 1, 1.5, 2, 3, 4, 6, 8,10, 12 and 24 hours post dose. Blood samples were centrifuged and plasma was separated and stored at -80 degree Celsius till time of analysis. Plasma concentrations of sildenafil were determined by liquid chromatography tandem mass spectrometry (LC/MS/MS)

Official Title
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Pharmacokinetics and Pharmacodynamics of Sildenafil in Adult Smokers and Non-smokers

Conditions
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Erectile Dysfunction, Smoking, Pharmacokinetics, Pharmacodynamics

Intervention / Treatment
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* Drug: Sildenafil 50 mg Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects Age 18-55 years. Ideal weight with ideal body mass index(BMI). Non-contributory history and normal physiological examination. Laboratory data within normal limits. Performance and compliance. The subjects should be without known history of alcohol or drug abuse problems Subjects who are cigarette smokers Subjects who are cannabis smokers Subjects who are non-smokers Exclusion Criteria: A known hypersensitivity to the drug. Gastrointestinal diseases. Auto immune diseases. Renal diseases or dysfunction. Cardiovascular disease of any type. Pancreatic disease including diabetes. Hepatic disease. Hematological, osteopathic, or pulmonary disease. History of alcoholism or drug abuse. Serious Psychological illness. Positive HIV. Abnormal (out of range) laboratory values. Subject who have taken any medication less than two weeks of the trials starting date. Subject who have donated blood or who have been in multiple dosing studies requiring a large volume of blood (more than 500 ml) to be drawn within six weeks preceding the start of the trials.

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Non-Smokers<br>Subjects administer one tablet of sildenafil 50 mg | Drug: Sildenafil 50 mg Oral Tablet<br>* Sildenafil 50 mg Oral Tablet<br>* Other names: Viagra 50 mg film coated tablets;|
| Experimental: Cigarette Smokers<br>Subjects administer one tablet of sildenafil 50mg | Drug: Sildenafil 50 mg Oral Tablet<br>* Sildenafil 50 mg Oral Tablet<br>* Other names: Viagra 50 mg film coated tablets;|
| Experimental: Cannabis Smokers<br>Subjects administer one tablet of sildenafil 50mg | Drug: Sildenafil 50 mg Oral Tablet<br>* Sildenafil 50 mg Oral Tablet<br>* Other names: Viagra 50 mg film coated tablets;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum drug concentration in plasma (Cmax) | Maximum drug concentration in plasma measured in nano-grams per milliliters (ng/ml) | up to 3 hours post-dose | 
| Area under the plasma concentration-time curve from time zero to the last quantifiable concentration post-dose (AUC0→t) | Area under the plasma concentration-time curve from time 0 to time(t) measured in nano-grams multiplied by hours and divided by milliliters (ng.h/ml) | up to 24 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Maximum drug concentration in plasma (tmax) | Time corresponding to maximum drug concentration in plasma measured in Hours(h) | up to 3 hours post-dose | 
| Elimination half life of drug in plasma ( t½) | Elimination half life of drug measured in Hours(hr) | Up to 24 hours post-dose | 
| Area under the plasma concentration-time curve from time 0 to infinity | Area under the plasma concentration-time curve from time 0 to infinity measured in nano-grams multiplied by hours and divided by milliliters (ng.h/ml) | Up to 24 hours post-dose |