Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The purpose of this study is to understand how an antibiotic, rifampin, may change the blood levels of another antibiotic, daptomycin, in the body. In addition, the effect of polymorphisms in P-glycoprotein (a protein involved in the removal of daptomycin from the body) on the blood levels of daptomycin will be evaluated. The hypotheses are that rifampin will decrease the blood levels of daptomycin and that the effect will be greater for certain P-glycoprotein polymorphisms.
This will be an open-label, sequential pharmacokinetic study in 12 healthy volunteers. After providing informed consent, participants meeting inclusion criteria will be administered daptomycin 6 mg/kg over 2 minutes and blood and urine samples will be collected over a 24 hour period after infusion. Following this, participants will be given a 13 day supply of rifampin 600 mg/day to be taken at home. After completion of the rifampin course, a second pharmacokinetic sampling will be performed (day 15 overall). Participants will be administered a dose of rifampin 600 mg then once again be administered daptomycin 6 mg/kg over 2 minutes and blood and urine samples will be collected over a second 24 hour period. A blood sample will be obtained at the first study visit for determination of each participant's P-glycoprotein genotype.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Daptomycin and Rifampin | Experimental | Drug: Daptomycin Daptomycin 6 mg/kg will be given by IV infusion on the first study day Drug: Rifampin Rifampin 600 mg capsules will be given orally once daily for 14 days starting on study day 2 Drug: Daptomycin Daptomycin 6 mg/kg will be given by IV infusion on study day 15 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Daptomycin | Drug |
|
| |
| Rifampin |
| Measure | Description | Time Frame |
|---|---|---|
| Daptomycin total, renal, and non-renal clearance | Total, renal, and non-renal clearance of daptomycin before and after administration of rifampin | 14 days |
| Daptomycin Volume of Distribution | The volume of distribution of daptomycin before and after administration of rifampin | 14 days |
| Daptomycin Elimination Rate Constant | The elimination rate constant of daptomycin before and after administration of rifampin | 14 days |
| Daptomycin Free and Total Peak Concentrations | The free and total peak concentrations of daptomycin before and after administration of rifampin | 14 days |
| Daptomycin Free and Total 24 hour Concentrations | The free and total 24 hour concentrations of daptomycin before and after administration of rifampin | 14 days |
| Daptomycin Free and Total Area Under the Concentration-Time Curve (AUC) from 0 to 24 hours | The free and total AUC from 0 to 24 hours of daptomycin before and after administration of rifampin | 14 days |
| Daptomycin Free and Total AUC from 0 to Infinity | The free and total AUC from 0 to infinity of daptomycin before and after administration of rifampin | 14 days |
| Measure | Description | Time Frame |
|---|---|---|
| P-glycoprotein Polymorphism | The effect of different P-glycoprotein polymorphisms on the pharmacokinetic profile of daptomycin before and after administration of rifampin will be assessed | 14 days |
| Number of Participants with Adverse Events |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Russell Benefield, Pharm.D. | University of Utah | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Utah | Salt Lake City | Utah | 84132 | United States |
Not provided
| ID | Term |
|---|---|
| D017576 | Daptomycin |
| D012293 | Rifampin |
| ID | Term |
|---|---|
| D010456 | Peptides, Cyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D055666 | Lipopeptides |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Drug |
|
|
| Percent Protein Binding of Daptomycin | The percent protein binding of daptomycin before and after administration of rifampin | 14 days |
Safety monitoring will be done by regular adverse event assessment, laboratory and vital sign monitoring, and physical exam.
| 45 days |
| D008055 |
| Lipids |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012294 | Rifamycins |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D047029 | Lactams, Macrocyclic |