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| Name | Class |
|---|---|
| St. Antonius Hospital | OTHER |
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The pharmacokinetics of fluconazole are expected to be different in obese patients compared to non-obese patients. The investigators will determine fluconazole and free fluconazole concentrations in 16 obese patients and 8 healthy volunteers, who will receive oral and intravenous fluconazole in a semi-simultaneous design.
A full pharmacokinetic curve will be obtained until 48 hours after intravenous administration.
The pharmacokinetics of fluconazole are expected to be different in obese patients compared to non-obese patients. Therefore, extrapolation of data from healthy volunteers and is not possible.
To investigate these differences 16 obese patients and 8 healthy subjects will be studied.
Patients will receive fluconazole by semi-simultaneous design. Blood sampling for pharmacokinetic analysis will be retrieved through a central venous catheter. A maximum of 100 milliliter blood in total will be drawn for this study. Patients will be monitored daily during the treatment period for adverse events of the study drug.
Full pharmacokinetic curves will be taken after oral and intravenous administration. This pharmacokinetic analysis will enable the determination of bioavailability and enable the determination of intra-individual variability.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Obese subjects | Experimental | Drug: Fluconazole tablet (diflucan) 200mg Single dose by oral administration of 400mg Drug: Fluconazole injection (diflucan) 400mg Single dose by intravenous infusion 400mg |
|
| Non-obese subjects | Active Comparator | Drug: Fluconazole tablet (diflucan) 200mg Single dose by oral administration of 400mg Drug: Fluconazole injection (diflucan) 400mg Single dose by intravenous infusion 400mg |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fluconazole 200mg tab | Drug | PO dose of 400mg |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area under the plasma concentration versus time curve (AUC) of fluconazole | The concentration-time curve of fluconazole will be compared with that in non-obese subjects. Exposure is assessed by area-under-the-curve from zero to 48 hours (AUC0-48h) | 48 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Area under the plasma concentration versus time curve (AUC) of fluconazole augmented dose | The concentration-time curve of fluconazole will be compared with that in non-obese subjects. Exposure is assessed by area-under-the-curve from zero to 48 hours (AUC0-48h) | 48 hours |
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Inclusion Criteria:
Subjects BMI:
Subject is at least 18 of age on the day of screening and not older than 65 years of age on the day of dosing;
Subject able and willing to sign the Informed Consent before screening evaluations.
If a woman, is neither pregnant nor able to become pregnant and is not nursing an infant.
For the non-obese subjects the following additional inclusion criteria applies:
Subject is in good age-appropriate health condition as established by medical history, physical examination, electrocardiography, results of biochemistry and hematology within 6 weeks prior to study drug administration. Results of biochemistry and hematology should be within the laboratory's reference ranges (see Appendix A). If laboratory results are not within the reference ranges, the subject is included based on the investigator's judgment that the observed deviations are not clinically relevant. This should be clearly recorded.
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| St. Antonius hospital | Nieuwegein | Netherlands | ||||
| Radboudumc |
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Comparing a 2 groups of obese subjects vs 1 group of non-obese subjects
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| Fluconazole 2 MG/ML | Drug | IV dose of 400mg |
|
|
| Nijmegen |
| Netherlands |
| ID | Term |
|---|---|
| D002177 | Candidiasis |
| D000072742 | Invasive Fungal Infections |
| D009765 | Obesity |
| D009181 | Mycoses |
| ID | Term |
|---|---|
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D015725 | Fluconazole |
| ID | Term |
|---|---|
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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