Study of the Relative Oral Bioavailability of the Antiflu Medicine Oseltamivir in the Intensive Care Unit

Study Overview
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Brief Summary
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This proposed pharmacokinetic study will test the hypothesis that in critically ill patients with respiratory failure requiring mechanical ventilation such as might be anticipated to be needed to treat patients with severe influenza pneumonia, oseltamivir administered enterally via nasogastric tube, with and without concomitant food or alimentation, will have similar oral bioavailability to that observed in ambulatory adults ill with influenza in whom oseltamivir therapy 75 mg BID is efficacious and well tolerated. Additionally, this experiment will test the hypothesis that increasing the dose (150 mg), with and without concomitant enteral feeding, will show a proportionate increase in bioavailability. Relative oral bioavailability will be assessed from plasma concentration vs. time over 12 hrs and urinary recovery of drug from 0 to 48 hrs after administration.

Detailed Description
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Not required

Official Title
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A Study of the Relative Oral Bioavailability of the Antiflu Medicine Oseltamivir (Tamiflu®) in Patients in the Intensive Care Unit

Conditions
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Influenza A Virus Infection, Influenza B Virus Infection

Intervention / Treatment
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* Drug: Oseltamivir 75 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients admitted to the Intensive Care Unit requiring mechanical ventilation due to respiratory failure must be within the ages of 18-75 yrs Exclusion Criteria: patients unable to have enteral feeding intolerance to oseltamivir pregnancy gastrointestinal or malabsorptive disease intestinal bypass surgery diarrhea (>2 loose bowel movements per day) receipt of prokinetic medications (metoclopramide, domperidone, erythromycin) severe liver disease (hepatocellular enzymes > 3 times the upper limit of normal) renal failure (Cockroft-Gault Creatinine Clearance < 30 ml/min, Dialysis dependant) cystic fibrosis intoxication or drug overdose

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A.Oseltamivir 75 mg dose<br>Patients will be randomized to two groups (group A) to receive oseltamivir at 75 mg, or (group B) to receive the drug at 150 mg in the fasting or fed state. | Drug: Oseltamivir 75 mg<br>* The primary objective of this study is to demonstrate that the pharmacokinetics of oseltamivir, when given enterally to critically ill patients, in the standard treatment dose of 75 mg or double that dose, 150 mg, will yield a plasma concentration - versus - Time Area under the curve (AUC) similar to that observed in adults with influenza treated successfully with a dose of 75 mg, that the disposition characteristics are dose proportionate and are not altered by the concomitant administration of enteral feedings.<br>* Other names: Tamiflu;|
| Active Comparator: B. Oseltamivir 150mg<br>Patients will be randomized to groups (group A) to receive oseltamivir at 75 mg, or group B to receive the drug at 150 mg in the fasting or fed state. | Drug: Oseltamivir 75 mg<br>* The primary objective of this study is to demonstrate that the pharmacokinetics of oseltamivir, when given enterally to critically ill patients, in the standard treatment dose of 75 mg or double that dose, 150 mg, will yield a plasma concentration - versus - Time Area under the curve (AUC) similar to that observed in adults with influenza treated successfully with a dose of 75 mg, that the disposition characteristics are dose proportionate and are not altered by the concomitant administration of enteral feedings.<br>* Other names: Tamiflu;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oseltamivir administered enterally via nasogastric tube, with and without concomitant food or alimentation, will have similar oral bioavailability to that observed in ambulatory adults . |  | 13 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Test the hypothesis that increasing the dose (150 mg), with and without concomitant enteral feeding, will show a proportionate increase in bioavailability. |  | 13 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prevention or treatment of influenza in ventilated patients