Drug Interactions, Intestinal Transporter Expression, Pharmacodynamics, Pharmacokinetics
Conditions
Brief summary
The purpose of this study is to evaluate the effects of a chronic co-medication of efavirenz on pharmacokinetics and sterol-lowering effects of ezetimibe at steady-state in healthy subjects genotyped for ABCB1, ABCC2, CYP2B6 and UGT1A1.
Interventions
DRUGEzetrol (ezetimibe) multiple dose
administration of 1 tablet/day Ezetrol (10 mg ezetimibe) on study day 6-15 and a pharmakokinetic on study day 15 (0-24 h blood sampling, 0-24 h urine sampling and 5 d feces sampling (study day 11-15))
DRUGEzetrol (ezetimibe) multiple dose and Sustiva (efavirenz) single dose
administration of 1 tablet/day Ezetrol(R) (10 mg ezetimibe) on study day 16-20 and 2 capsules Sustiva(R) (2x200 mg efavirenz) on study day 16 with a pharmakokinetic (0-120 h blood sampling, urine sampling (24 h intervals) and feces sampling on study days 16-20)
DRUGEzetrol (ezetimibe) and Sustiva (efavirenz) multiple dose
administration of 1 tablet/day Ezetrol(R) (10 mg ezetimibe) and 2 capsules/day Sustiva(R) (2x200 mg efavirenz) on study day 21-30 and with a pharmakokinetic (0-120 h blood sampling, urine sampling (24 h intervals) on study day 30 and feces sampling on study day 26-30)
DRUGSustiva (efavirenz) single dose
administration of 2 capsules Sustiva(R) (2x200 mg efavirenz) on study day 1 with a pharmakokinetic (0-120 h blood sampling, urine sampling (24 h intervals) and feces sampling on study days 1-5)
Sponsors
University Medicine Greifswald
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* age: 18 - 45 years * sex: male and female * ethnic origin: Caucasian * body weight: 19 to 27 kg/m² * good health as evidenced by the results of the clinical examination, ECG, and the laboratory check-up, which are judged by the clinical investigator not to differ in a clinical relevant way from the normal state * written informed consent
Exclusion criteria
* existing cardiac or haematological diseases and/or pathological findings, which might interfere with the drug's safety, tolerability, absorption and/or pharmacokinetics * existing hepatic and renal diseases and/or pathological findings, which might interfere with the drug's safety, tolerability, absorption and/or pharmacokinetics * existing gastrointestinal diseases and/or pathological findings, which might interfere with the drug's safety, tolerability, absorption and/or pharmacokinetics * acute or chronic diseases which could affect drug absorption or metabolism * history of any serious psychological disorder * drug or alcohol dependence * positive drug or alcohol screening * smokers of 10 or more cigarettes per day * positive anti-HIV-test, HBs-Ag-test or anti-HCV-test * volunteers who are on a diet which could affect the pharmacokinetics of the drug * heavy tea or coffee drinkers (more than 1L per day) * lactation and pregnancy test positive or not performed * volunteers suspected or known not to follow instructions * volunteers who are unable to understand the written and verbal instructions, in particular regarding the risks and inconveniences they will be exposed to as a result of their participation in the study * volunteers liable to orthostatic dysregulation, fainting, or blackouts * blood donation or other blood loss of more than 400 ml within the last 12 weeks prior to the start of the study * participation in a clinical trial during the last 3 months prior to the start of the study * less than 14 days after last acute disease * any systemically available medication within 4 weeks prior to the intended first administration unless because of the terminal elimination half-life complete elimination from the body can be assumed for the drug and/or its primary metabolites (except oral contraceptives) * repeated use of drugs during the last 4 weeks prior to the intended first administration, which can influence hepatic biotransformation (e.g. barbiturates, cimetidine, phenytoin, rifampicin) * repeated use of drugs during the last 2 weeks prior to the intended first administration which affect absorption (e.g. laxatives, metoclopramide, loperamide, antacids, H2-receptor antagonists) * intake of grapefruit containing food or beverages within 7 days prior to administration * known allergic reactions to the active ingredients used or to constituents of the pharmaceutical preparation * subjects with severe allergies or multiple drug allergies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax of Efavirenz (Steady State Pharmacokinetic After Chronic Treatment With 400 mg Efavirenz and Concomitant Chronic Treatment of 10 mg Ezetimibe) on Study Day 30 | study day 30 | The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of efavirenz in the blood samplings. |
| Cmax of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Chronic Treatment With 400 mg Efavirenz) on Study Day 30 | study day 30 | The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of free ezetimibe in the blood samplings. |
| AUC of Efavirenz (Single Dose Pharmacokinetic After Treatment With 400 mg Efavirenz) on Study Days 1-5 | study days 1-5 | The area under the concentrations-time curve (AUC) was calculated with the measured data points from the time of administration until the last quantificable concentration by the trapezoidal formula and the extrapolation to infinity. The concentration-time curve is the result of time points of blood sampling and its measured concentration of efavirenz in the blood samplings. |
| AUC of Efavirenz (Single Dose Pharmacokinetic After Treatment With 400 mg Efavirenz and Concomitant Chronic Treatment of 10 mg Ezetimibe) on Study Days 16-20 | study days 16-20 | The area under the concentrations-time curve (AUC) was calculated with the measured data points from the time of administration until the last quantificable concentration by the trapezoidal formula and the extrapolation to infinity. The concentration-time curve is the result of time points of blood sampling and its measured concentration of efavirenz in the blood samplings. |
| AUC0-24h of Efavirenz (Steady State Pharmacokinetic After Chronic Treatment With 400 mg Efavirenz and Concomitant Chronic Treatment of 10 mg Ezetimibe) on Study Day 30 | study day 30 | The area under the concentrations-time curve (AUC0-24) was calculated with the measured data points from the time of administration up to 24 h after administration by the trapezoidal formula. The concentration-time curve is the result of time points of blood sampling and its measured concentration of efavirenz in the blood samplings. |
| Cmax of Efavirenz (Single Dose Pharmacokinetic After Treatment With 400 mg Efavirenz) on Study Days 1-5 | study days 1-5 | The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of efavirenz in the blood samplings. |
| Cmax of Efavirenz (Single Dose Pharmacokinetic After Treatment With 400 mg Efavirenz and Concomitant Chronic Treatment of 10 mg Ezetimibe) on Study Days 16-20 | study days 16-20 | The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of efavirenz in the blood samplings. |
| AUC0-24h of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe) on Study Day 15 | study day 15 | The area under the concentrations-time curve (AUC0-24) was calculated with the measured data points from the time of administration up to 24 h after administration by the trapezoidal formula. The concentration-time curve is the result of time points of blood sampling and its measured concentration of free ezetimibe in the blood samplings. |
| AUC0-24h of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Single Dose Administration of 400 mg Efavirenz) on Study Day 16 | study day 16 | The area under the concentrations-time curve (AUC0-24) was calculated with the measured data points from the time of administration up to 24 h after administration by the trapezoidal formula. The concentration-time curve is the result of time points of blood sampling and its measured concentration of free ezetimibe in the blood samplings. |
| AUC0-24h of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Chronic Treatment With 400 mg Efavirenz) on Study Day 30 | study day 30 | The area under the concentrations-time curve (AUC0-24) was calculated with the measured data points from the time of administration up to 24 h after administration by the trapezoidal formula. The concentration-time curve is the result of time points of blood sampling and its measured concentration of free ezetimibe in the blood samplings. |
| Cmax of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe) on Study Day 15 | study day 15 | The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of free ezetimibe in the blood samplings. |
| Cmax of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Single Dose Administration of 400 mg Efavirenz) on Study Day 16 | study day 16 | The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of free ezetimibe in the blood samplings. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-24h of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Single Dose Administration of 400 mg Efavirenz) on Study Day 16 | study day 16 | The area under the concentrations-time curve (AUC0-24) was calculated with the measured data points from the time of administration up to 24 h after administration by the trapezoidal formula. The concentration-time curve is the result of time points of blood sampling and its measured concentration of ezetimibe glucuronide in the blood samplings. |
| AUC0-24h of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Chronic Treatment With 400 mg Efavirenz) on Study Day 30 | study day 30 | The area under the concentrations-time curve (AUC0-24) was calculated with the measured data points from the time of administration up to 24 h after administration by the trapezoidal formula. The concentration-time curve is the result of time points of blood sampling and its measured concentration of ezetimibe glucuronide in the blood samplings. |
| Cmax of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe) on Study Day 15 | study day 15 | The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of ezetimibe glucuronide in the blood samplings. |
| Cmax of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Single Dose Administration of 400 mg Efavirenz) on Study Day 16 | study day 16 | The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of ezetimibe glucuronide in the blood samplings. |
| Cmax of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Chronic Treatment With 400 mg Efavirenz) on Study Day 30 | study day 30 | The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of ezetimibe glucuronide in the blood samplings. |
| AUC0-24h of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe) on Study Day 15 | study day 15 | The area under the concentrations-time curve (AUC0-24) was calculated with the measured data points from the time of administration up to 24 h after administration by the trapezoidal formula. The concentration-time curve is the result of time points of blood sampling and its measured concentration of ezetimibe glucuronide in the blood samplings. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Study Group whole study group: 12 healthy subjects | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Study Group |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age Continuous | 26 years STANDARD_DEVIATION 4.6 |
| Region of Enrollment Germany | 12 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 11 / 12 | 8 / 12 | 3 / 12 | 7 / 12 | 7 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 |
Outcome results
Primary
AUC0-24h of Efavirenz (Steady State Pharmacokinetic After Chronic Treatment With 400 mg Efavirenz and Concomitant Chronic Treatment of 10 mg Ezetimibe) on Study Day 30
The area under the concentrations-time curve (AUC0-24) was calculated with the measured data points from the time of administration up to 24 h after administration by the trapezoidal formula. The concentration-time curve is the result of time points of blood sampling and its measured concentration of efavirenz in the blood samplings.
Time frame: study day 30
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | AUC0-24h of Efavirenz (Steady State Pharmacokinetic After Chronic Treatment With 400 mg Efavirenz and Concomitant Chronic Treatment of 10 mg Ezetimibe) on Study Day 30 | 11.4 ng*h/ml | Standard Deviation 4.64 |
Comparison: Paired Wilcoxon-test between steady state pharmakokinetic of efavirenz with chronic treatment of ezetimibe and the single dose pharmakokinetic of efavirenz without chronic treatment of ezetimibe.p-value: <0.05Wilcoxon (Mann-Whitney)
Comparison: Paired Wilcoxon-test between steady state pharmakokinetic of efavirenz with chronic treatment of ezetimibe and the single dose pharmakokinetic of efavirenz with chronic treatment of ezetimibe.p-value: <0.05Wilcoxon (Mann-Whitney)
Primary
AUC0-24h of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Chronic Treatment With 400 mg Efavirenz) on Study Day 30
The area under the concentrations-time curve (AUC0-24) was calculated with the measured data points from the time of administration up to 24 h after administration by the trapezoidal formula. The concentration-time curve is the result of time points of blood sampling and its measured concentration of free ezetimibe in the blood samplings.
Time frame: study day 30
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | AUC0-24h of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Chronic Treatment With 400 mg Efavirenz) on Study Day 30 | 51.2 ng*h/ml | Standard Deviation 23.1 |
Primary
AUC0-24h of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Single Dose Administration of 400 mg Efavirenz) on Study Day 16
The area under the concentrations-time curve (AUC0-24) was calculated with the measured data points from the time of administration up to 24 h after administration by the trapezoidal formula. The concentration-time curve is the result of time points of blood sampling and its measured concentration of free ezetimibe in the blood samplings.
Time frame: study day 16
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | AUC0-24h of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Single Dose Administration of 400 mg Efavirenz) on Study Day 16 | 58.6 ng*h/ml | Standard Deviation 23.7 |
Primary
AUC0-24h of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe) on Study Day 15
The area under the concentrations-time curve (AUC0-24) was calculated with the measured data points from the time of administration up to 24 h after administration by the trapezoidal formula. The concentration-time curve is the result of time points of blood sampling and its measured concentration of free ezetimibe in the blood samplings.
Time frame: study day 15
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | AUC0-24h of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe) on Study Day 15 | 51.9 ng*h/ml | Standard Deviation 21.7 |
Primary
AUC of Efavirenz (Single Dose Pharmacokinetic After Treatment With 400 mg Efavirenz and Concomitant Chronic Treatment of 10 mg Ezetimibe) on Study Days 16-20
The area under the concentrations-time curve (AUC) was calculated with the measured data points from the time of administration until the last quantificable concentration by the trapezoidal formula and the extrapolation to infinity. The concentration-time curve is the result of time points of blood sampling and its measured concentration of efavirenz in the blood samplings.
Time frame: study days 16-20
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | AUC of Efavirenz (Single Dose Pharmacokinetic After Treatment With 400 mg Efavirenz and Concomitant Chronic Treatment of 10 mg Ezetimibe) on Study Days 16-20 | 27.0 ng*h/ml | Standard Deviation 12.2 |
Comparison: Paired Wilcoxon-test between steady state pharmakokinetic of efavirenz with chronic treatment of ezetimibe and the single dose pharmakokinetic of efavirenz with chronic treatment of ezetimibe.p-value: <0.05Wilcoxon (Mann-Whitney)
Primary
AUC of Efavirenz (Single Dose Pharmacokinetic After Treatment With 400 mg Efavirenz) on Study Days 1-5
The area under the concentrations-time curve (AUC) was calculated with the measured data points from the time of administration until the last quantificable concentration by the trapezoidal formula and the extrapolation to infinity. The concentration-time curve is the result of time points of blood sampling and its measured concentration of efavirenz in the blood samplings.
Time frame: study days 1-5
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | AUC of Efavirenz (Single Dose Pharmacokinetic After Treatment With 400 mg Efavirenz) on Study Days 1-5 | 29.7 ng*h/ml | Standard Deviation 15.4 |
Comparison: Paired Wilcoxon-test between steady state pharmakokinetic of efavirenz with chronic treatment of ezetimibe and the single dose pharmakokinetic of efavirenz without chronic treatment of ezetimibe.p-value: <0.05Wilcoxon (Mann-Whitney)
Primary
Cmax of Efavirenz (Single Dose Pharmacokinetic After Treatment With 400 mg Efavirenz and Concomitant Chronic Treatment of 10 mg Ezetimibe) on Study Days 16-20
The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of efavirenz in the blood samplings.
Time frame: study days 16-20
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | Cmax of Efavirenz (Single Dose Pharmacokinetic After Treatment With 400 mg Efavirenz and Concomitant Chronic Treatment of 10 mg Ezetimibe) on Study Days 16-20 | 0.659 ng/ml | Standard Deviation 0.395 |
Comparison: Paired Wilcoxon-test between steady state pharmakokinetic of efavirenz with chronic treatment of ezetimibe and the single dose pharmakokinetics of efavirenz with chronic treatment of ezetimibe.p-value: <0.05Wilcoxon (Mann-Whitney)
Primary
Cmax of Efavirenz (Single Dose Pharmacokinetic After Treatment With 400 mg Efavirenz) on Study Days 1-5
The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of efavirenz in the blood samplings.
Time frame: study days 1-5
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | Cmax of Efavirenz (Single Dose Pharmacokinetic After Treatment With 400 mg Efavirenz) on Study Days 1-5 | 0.622 ng/ml | Standard Deviation 0.244 |
Comparison: Paired Wilcoxon-test between steady state pharmakokinetic of efavirenz with chronic treatment of ezetimibe and the single dose pharmakokinetic of efavirenz without chronic treatment of ezetimibe.p-value: <0.05Wilcoxon (Mann-Whitney)
Primary
Cmax of Efavirenz (Steady State Pharmacokinetic After Chronic Treatment With 400 mg Efavirenz and Concomitant Chronic Treatment of 10 mg Ezetimibe) on Study Day 30
The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of efavirenz in the blood samplings.
Time frame: study day 30
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | Cmax of Efavirenz (Steady State Pharmacokinetic After Chronic Treatment With 400 mg Efavirenz and Concomitant Chronic Treatment of 10 mg Ezetimibe) on Study Day 30 | 0.918 ng/ml | Standard Deviation 0.342 |
Comparison: Paired Wilcoxon-test between steady state pharmakokinetic of efavirenz with chronic treatment of ezetimibe and the single dose pharmakokinetic of efavirenz without chronic treatment of ezetimibe.p-value: <0.05Wilcoxon (Mann-Whitney)
Comparison: Paired Wilcoxon-test between steady state pharmakokinetic of efavirenz with chronic treatment of ezetimibe and the single dose pharmakokinetics of efavirenz with chronic treatment of ezetimibe.p-value: <0.05Wilcoxon (Mann-Whitney)
Primary
Cmax of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Chronic Treatment With 400 mg Efavirenz) on Study Day 30
The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of free ezetimibe in the blood samplings.
Time frame: study day 30
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | Cmax of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Chronic Treatment With 400 mg Efavirenz) on Study Day 30 | 4.46 ng/ml | Standard Deviation 2.07 |
Primary
Cmax of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Single Dose Administration of 400 mg Efavirenz) on Study Day 16
The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of free ezetimibe in the blood samplings.
Time frame: study day 16
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | Cmax of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Single Dose Administration of 400 mg Efavirenz) on Study Day 16 | 5.54 ng/ml | Standard Deviation 2.65 |
Comparison: Paired Wilcoxon-test between free ezetimibe alone and free ezetimibe with single dose treatment of efavirenz.p-value: <0.05Wilcoxon (Mann-Whitney)
Primary
Cmax of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe) on Study Day 15
The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of free ezetimibe in the blood samplings.
Time frame: study day 15
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | Cmax of Free Ezetimibe (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe) on Study Day 15 | 4.82 ng/ml | Standard Deviation 2.74 |
Comparison: Paired Wilcoxon-test between free ezetimibe alone and free ezetimibe with single dose treatment of efavirenz.p-value: <0.05Wilcoxon (Mann-Whitney)
Secondary
AUC0-24h of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Chronic Treatment With 400 mg Efavirenz) on Study Day 30
The area under the concentrations-time curve (AUC0-24) was calculated with the measured data points from the time of administration up to 24 h after administration by the trapezoidal formula. The concentration-time curve is the result of time points of blood sampling and its measured concentration of ezetimibe glucuronide in the blood samplings.
Time frame: study day 30
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | AUC0-24h of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Chronic Treatment With 400 mg Efavirenz) on Study Day 30 | 325 ng*h/ml | Standard Deviation 152 |
Comparison: Paired Wilcoxon-test between free ezetimibe with chronic treatment of efavirenz and free ezetimibe alone.p-value: <0.05Wilcoxon (Mann-Whitney)
Comparison: Paired Wilcoxon-test between free ezetimibe with chronic treatment of efavirenz and free ezetimibe with single dose treatment of efavirenz.p-value: <0.05Wilcoxon (Mann-Whitney)
Secondary
AUC0-24h of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Single Dose Administration of 400 mg Efavirenz) on Study Day 16
The area under the concentrations-time curve (AUC0-24) was calculated with the measured data points from the time of administration up to 24 h after administration by the trapezoidal formula. The concentration-time curve is the result of time points of blood sampling and its measured concentration of ezetimibe glucuronide in the blood samplings.
Time frame: study day 16
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | AUC0-24h of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Single Dose Administration of 400 mg Efavirenz) on Study Day 16 | 411 ng*h/ml | Standard Deviation 195 |
Comparison: Paired Wilcoxon-test between free ezetimibe alone and free ezetimibe with single dose treatment of efavirenz.p-value: <0.05Wilcoxon (Mann-Whitney)
Comparison: Paired Wilcoxon-test between free ezetimibe with chronic treatment of efavirenz and free ezetimibe with single dose treatment of efavirenz.p-value: <0.05Wilcoxon (Mann-Whitney)
Secondary
AUC0-24h of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe) on Study Day 15
The area under the concentrations-time curve (AUC0-24) was calculated with the measured data points from the time of administration up to 24 h after administration by the trapezoidal formula. The concentration-time curve is the result of time points of blood sampling and its measured concentration of ezetimibe glucuronide in the blood samplings.
Time frame: study day 15
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | AUC0-24h of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe) on Study Day 15 | 466 ng*h/ml | Standard Deviation 223 |
Comparison: Paired Wilcoxon-test between free ezetimibe alone and free ezetimibe with single dose treatment of efavirenz.p-value: <0.05Wilcoxon (Mann-Whitney)
Comparison: Paired Wilcoxon-test between free ezetimibe with chronic treatment of efavirenz and free ezetimibe alone.p-value: <0.05Wilcoxon (Mann-Whitney)
Secondary
Cmax of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Chronic Treatment With 400 mg Efavirenz) on Study Day 30
The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of ezetimibe glucuronide in the blood samplings.
Time frame: study day 30
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | Cmax of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Chronic Treatment With 400 mg Efavirenz) on Study Day 30 | 45.3 ng/ml | Standard Deviation 14.6 |
Comparison: Paired Wilcoxon-test between free ezetimibe with chronic treatment of efavirenz and free ezetimibe alone.p-value: <0.05Wilcoxon (Mann-Whitney)
Comparison: Paired Wilcoxon-test between free ezetimibe with chronic treatment of efavirenz and free ezetimibe with single dose treatment of efavirenz.p-value: <0.05Wilcoxon (Mann-Whitney)
Secondary
Cmax of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Single Dose Administration of 400 mg Efavirenz) on Study Day 16
The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of ezetimibe glucuronide in the blood samplings.
Time frame: study day 16
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | Cmax of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe and Concomitant Single Dose Administration of 400 mg Efavirenz) on Study Day 16 | 60.9 ng/ml | Standard Deviation 29.5 |
Comparison: Paired Wilcoxon-test between free ezetimibe with chronic treatment of efavirenz and free ezetimibe with single dose treatment of efavirenz.p-value: <0.05Wilcoxon (Mann-Whitney)
Secondary
Cmax of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe) on Study Day 15
The maximum concentration (Cmax) were obtained directly from the measured concentration-time curves. The concentration-time curve is the result of time points of blood sampling and its measured concentration of ezetimibe glucuronide in the blood samplings.
Time frame: study day 15
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | Cmax of Ezetimibe Glucuronide (Steady-state Pharmacokinetic After Chronic Treatment With 10 mg Ezetimibe) on Study Day 15 | 79.0 ng/ml | Standard Deviation 43.1 |
Comparison: Paired Wilcoxon-test between free ezetimibe with chronic treatment of efavirenz and free ezetimibe alone.p-value: <0.05Wilcoxon (Mann-Whitney)