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The aim of this study is to understand the behavior of posaconazol gives as a suspension and solution in the gastrointestinal tract in human volunteers. The investigators know that supersaturation for this compound can be achieved by the influence of the gastrointestinal tract: The acid environment of the stomach creates a optimized environment for the basic compound to reach a high solubility, while the neutral environment of the small intestine creates a low solubility environment for the compound. The transit from stomach to small intestine gives the opportunity for the drug to create a supersaturated solution. Giving the drug as a solution to the healthy volunteer makes sure that precipitation is not occurring in the stomach and that precipitation has to happen in the small intestine. After all, supersaturation is a state that is not thermodynamic stable and always will want to precipitate. Giving the drug as a suspension to the healthy volunteers, can make it possible that still some particles of the drug are not in dissolution and that those particles will flow to the small intestine where other particles easily can bind to. This will make that almost the whole supersaturated solution is immediately precipitated.
The investigators want to give the suspension by the authorized drug called Noxafil. On the other hand an aqueous solution will be made by adjusting the pH to 1.2 (which is conform with the pH of the stomach) and given to the volunteers by the stomach catheter. This 2 formulations will be tested in a fasted state and a fed state (by giving 2 Ensure plus shakes to the volunteers before the experiment starts). After intake of the formulation, gastric and duodenal fluids will be aspirated by the catheters and analyzed at their laboratory. So the four conditions the investigators want to study are:
By getting more knowledge about the behavior of posaconazol (interplay supersaturation / precipitation) more insights can be achieved for the development of supersaturating drug delivery systems.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Suspension, fasted state | Experimental | Suspension Noxafil will be administered in the fasted state to the volunteers. |
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| Suspension, with sugar (delay gastric emptying) | Experimental | Suspension will be co-administered with glucose to delay the gastric emptying time |
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| Solution, fasted state | Experimental | A solution (by acidifying the suspension in water to pH 1.2) will be administered to healthy volunteers in a fasted state. |
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| Solution, with sugar (delaying gastric emptying) | Experimental | A solution of posaconazol (by acidifying the suspension in water to pH 1.2) will be administered together with sugar to delay the gastric emptying. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Suspension Fasted State | Drug |
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| Suspension Fed State |
| Measure | Description | Time Frame |
|---|---|---|
| Concentration-time profile in stomach and small intestine for posaconazol | These concentrations will be measured for 4 hours, together by taking blood samples to see how the drug will be transported to the blood circulation (PK profile for 48 hours) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Bart Hens, Pharmacist | Contact | +3216330302 | bart.hens@pharm.kuleuven.be |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UZ Leuven Gasthuisberg | Recruiting | Leuven | 3000 | Belgium |
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| Drug |
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| Solution Fasted State | Drug |
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| Solution Fed State | Drug |
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