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The purpose of this study is to evaluate the impact of genetic variants of OATP 1B3 or MRP 2 on the systemic disposition of endogenously formed CCK-8 and to determine the influence of a single-dose of the transporter inhibitor rifampin (600 mg) on the systemic disposition of endogenously formed CCK-8. Endogenous CCK-8 secretion will be induced by a single-dose standardized liquid mixed meal.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| mixed meal | Placebo Comparator |
| |
| mixed meal 2 h after single dose rifampin (600 mg) | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| mixed meal | Dietary Supplement | 250 ml Fortimel compact (chocolate) |
|
| Measure | Description | Time Frame |
|---|---|---|
| CCK-8 | Cholecystokinin amino acid 8 concentration in blood plasma | 3 h 15 min up to 2 h 15 min before and 5, 10, 15, 20, 25, 30, 45 min, 1, 1.25, 1.5, 2, 3, 4 h after mixed meal |
| Measure | Description | Time Frame |
|---|---|---|
| GLP-1 | Glucagon-like peptide-1 concentration in blood plasma | 3 h 15 min up to 2 h 15 min before and 5, 10, 15, 20, 25, 30, 45 min, 1, 1.25, 1.5, 2, 3, 4 h after mixed meal |
| GIP | Gastric inhibitory polypeptide concentration in blood plasma |
| Measure | Description | Time Frame |
|---|---|---|
| area under the curve AUC from zero to the last sampling time above the limit of quantitation (AUC0-t) of rifampin and DAc-RIF (25-O-desacetyl-rifampin) | 3 h 15 min up to 2 h 15 min, 1.5, 1 h before and 5 min, 1, 2, 3, 4, 6, 8, 10 and 14 h after mixed meal | |
| area under the curve AUC from zero to 4 h (AUC0-4h) of rifampin and DAc-RIF (25-O-desacetyl-rifampin) |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Werner Siegmund, Prof | Department of Clinical Pharmacology | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Clinical Pharmacology | Greifswald | 17489 | Germany |
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| ID | Term |
|---|---|
| D012293 | Rifampin |
| ID | Term |
|---|---|
| D012294 | Rifamycins |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| Rifampin | Drug | oral rifampin administration (600 mg EREMFAT®) |
|
| 3 h 15 min up to 2 h 15 min before and 5, 10, 15, 20, 25, 30, 45 min, 1, 1.25, 1.5, 2, 3, 4 h after mixed meal |
| glucagon | glucagon concentration in blood plasma | 3 h 15 min up to 2 h 15 min before and 5, 10, 15, 20, 25, 30, 45 min, 1, 1.25, 1.5, 2, 3, 4 h after mixed meal |
| glucose | glucose concentration in blood plasma | 3 h 15 min up to 2 h 15 min before and 15, 30, 45 min, 1, 1.25 h after mixed meal |
| potassium | potassium concentration in blood plasma | 3 h 15 min up to 2 h 15 min before and 15, 30, 45 min, 1, 1.25 h after mixed meal |
| C-peptide | connecting peptide concentration in blood plasma | 3 h 15 min up to 2 h 15 min before and 15, 30, 45 min, 1, 1.25 h after mixed meal |
| insulin | insulin concentration in blood plasma | 3 h 15 min up to 2 h 15 min before and 15, 30, 45 min, 1, 1.25 h after mixed meal |
| 3 h 15 min up to 2 h 15 min, 1.5, 1 h before and 5 min, 1, 2 h after mixed meal |
| maximal concentration (Cmax) of rifampin and DAc-RIF (25-O-desacetyl-rifampin) | 3 h 15 min up to 2 h 15 min, 1.5, 1 h before and 5 min, 1, 2, 3, 4, 6, 8, 10 and 14 h after mixed meal |
| time point of maximal concentration (tmax) of rifampin and DAc-RIF (25-O-desacetyl-rifampin) | 3 h 15 min up to 2 h 15 min, 1.5, 1 h before and 5 min, 1, 2, 3, 4, 6, 8, 10 and 14 h after mixed meal |
| terminal half-life (t1/2) of rifampin and DAc-RIF (25-O-desacetyl-rifampin) | 3 h 15 min up to 2 h 15 min, 1.5, 1 h before and 5 min, 1, 2, 3, 4, 6, 8, 10 and 14 h after mixed meal |
| D047029 | Lactams, Macrocyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |