Evaluate Two Paradigms for Simultaneous Assessment of Hepatic and Intestinal CYP3A
Conditions
Brief summary
To evaluate two paradigms for simultaneous assessment of hepatic and intestinal CYP3A activity.
Interventions
DRUGAlfentanil
No drug treatment before alfentanil
Sponsors
National Institute of General Medical Sciences (NIGMS)
Washington University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or non-pregnant female, 18-40 yr. old * Good general health with no remarkable medical conditions such as liver, kidney, heart, or lung failure * BMI between 20-33 * Provide informed consent
Exclusion criteria
* Known history of liver or kidney disease * Use of prescription or non prescription medications, herbals or foods known to be metabolized by or affect CYP3A (including oral birth control medications) * Females who are pregnant or nursing * Known history of drug or alcohol addiction (prior or present addiction or treatment for addiction) * Direct physical access to and routine handling of addicting drugs in the regular course of duty (this is a routine exclusion from studies of drugs with addiction potential). * History of bradycardia * Respiratory rate \<10 * History of significant pulmonary disease * History of pre-existing medical condition predisposing to respiratory depression * Systolic blood pressure \<100 mgHg and diastolic blood pressure \<70mmHg
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve of Alfentanil Concentration vs. Time Extrapolated to Infinity | 9 hours | AUC(0-inf) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Alfentanil | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | Alfentanil |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 3 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 | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 0 / 6 | 0 / 6 | 1 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Area Under the Curve of Alfentanil Concentration vs. Time Extrapolated to Infinity
AUC(0-inf)
Time frame: 9 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alfentanil | Area Under the Curve of Alfentanil Concentration vs. Time Extrapolated to Infinity | Simultaneous Control | 58 (hr*ng/ml/mg) | Standard Deviation 15 |
| Alfentanil | Area Under the Curve of Alfentanil Concentration vs. Time Extrapolated to Infinity | Simultaneous Rifampin | 57 (hr*ng/ml/mg) | Standard Deviation 9 |
| Alfentanil | Area Under the Curve of Alfentanil Concentration vs. Time Extrapolated to Infinity | Simultaneous Grapefruit | 55 (hr*ng/ml/mg) | Standard Deviation 12 |
| Alfentanil | Area Under the Curve of Alfentanil Concentration vs. Time Extrapolated to Infinity | Simultaneous ketoconazole | 73 (hr*ng/ml/mg) | Standard Deviation 26 |
| Alfentanil | Area Under the Curve of Alfentanil Concentration vs. Time Extrapolated to Infinity | Sequential Control | 59 (hr*ng/ml/mg) | Standard Deviation 27 |
| Alfentanil | Area Under the Curve of Alfentanil Concentration vs. Time Extrapolated to Infinity | Sequential Rifampin | 54 (hr*ng/ml/mg) | Standard Deviation 10 |
| Alfentanil | Area Under the Curve of Alfentanil Concentration vs. Time Extrapolated to Infinity | Sequential Grapefruit | 59 (hr*ng/ml/mg) | Standard Deviation 31 |
| Alfentanil | Area Under the Curve of Alfentanil Concentration vs. Time Extrapolated to Infinity | Sequential Ketoconazole | 73 (hr*ng/ml/mg) | Standard Deviation 19 |
p-value: <0.05ANOVA