Investigation of Gender Specificity of the Effects of Furosemide in Healthy Female and Male Volunteers

Study Overview
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Brief Summary
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In this study the gender specificity of the effects of furosemide in female and male volunteers will be investigated. The main objective is gender-specific comparison of the pharmacokinetic parameters of furosemide in relation to the effect of furosemide (urinary excretion). Secondary objectives are the gender-specific comparison of renal and systemic PAH clearance with the clearance of furosemide and the influence of various genetic polymorphisms on the variability of furosemide pharmacokinetics.

Detailed Description
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In this study the gender specificity of the effects of furosemide in female and male volunteers will be investigated. The healthy volunteers receive 1. furosemide and 2. aminohippurate sodium PAH as single dose. The main objective is gender-specific comparison of the pharmacokinetic parameters of furosemide in relation to the effect of furosemide (urinary excretion). Secondary objectives are the gender-specific comparison of renal and systemic PAH clearance with the clearance of furosemide and the influence of various genetic polymorphisms on the variability of furosemide pharmacokinetics.

Official Title
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Investigation of Gender Specificity of the Effects of Furosemide in Healthy Female and Male Volunteers

Conditions
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Healthy Male and Female Volunteers

Intervention / Treatment
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* Drug: Furosemide
* Drug: aminohippurate sodium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteer for medical history and physical examination findings 18 years, <40 years Written informed consent is given No clinically relevant changes in laboratory parameters Inconspicuous current ECG taking medication under a different drug trial within the last 30 days Exclusion Criteria: concomitant medication at study days or a week before allergies or known hypersensitivity reactions to furosemide or aminohippurate sodium decreased creatinine clearance by Cockcroft-Gault (<100 ml / min) current drug abuses opiate addiction within the last 10 years smoking within the last year pregnancy and 6 months postpartum, lactation deprivation of legal capacity Cooperation inability

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 39 Years

Sexes Eligible for Study
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All

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: female<br>The healthy female volunteers receive furosemide and aminohippurate sodium PAH as single dose randomised on day 1 or day 2. | Drug: Furosemide<br>* Injection, 40 mg, single dose over 5 min<br>* Other names: Product name: Lasix 40 mg Injektionslösung;Drug: aminohippurate sodium<br>* Injection, 500 mg, single dose over 5 min<br>* Other names: Product name: Aminohipppurate Sodium PAH;|
| Experimental: male<br>The healthy male volunteers receive furosemide and aminohippurate sodium PAH as single dose randomised on day 1 or day 2 | Drug: Furosemide<br>* Injection, 40 mg, single dose over 5 min<br>* Other names: Product name: Lasix 40 mg Injektionslösung;Drug: aminohippurate sodium<br>* Injection, 500 mg, single dose over 5 min<br>* Other names: Product name: Aminohipppurate Sodium PAH;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pharmacokinetic parameter of furosemide (AUC-24) | Gender-specific comparison of the pharmacokinetic parameters of furosemide (AUC-24). The sample size calculation for this study was conducted with respect to the expected gender difference in the AUC24 of furosemide. | day 1 or day 2 | 
| pharmacodynamic parameter of furosemide (Sodium excretion in the urine) | Gender-specific comparison of effect of furosemide on urinary excretion (sodium) | day 1 or day 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pharmacogenetic parameters | Influence of various genetic polymorphism (OAT1, OAT 4, OATP1B1, NKCC2, NCC, ENaC) on the variability of pharmacokinetic of furosemide | day 1 | 
| pharmacokinetic of aminohippuric acid | gender-specific comparison of renal and systemic PAH clearance with the clearance of furosemide | day 1 or day 2 | 
| other pharmacokinetic parameter of furosemide | Gender-specific comparison of the other pharmacokinetic parameters of furosemide (Cmax, tmax, t½, CLoral, CLren) | day 1 or day 2 | 
| other pharmacodynamic parameter of furosemide | Gender-specific comparison of effect of furosemide on urinary excretion (chloride, potassium, uric acid, calcium, magnesium, creatinine) | day 1 or day 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gender, diuretics, furosemide, aminohippuric acid