Healthy Volunteers
Conditions
Keywords
ketamine polymorphisms
Brief summary
This research study will determine if genetic variation in CYP2B6 affects how the body metabolizes ketamine.
Interventions
DRUGketamine
0.4 mg/kg oral racemic ketamine
Sponsors
Washington University School of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. 18-50 yr old 2. CYP2B6\*1/\*1, CYP2B6\*1/\*6 or CYP2B6\*6/\*6 genotype (see table) (Note: subjects of other rare genotype but with one or more 516G\>T, 785A\>G, 983T\>C or 1459C\>T polymorphism may be enrolled at PI's discretion) 3. Good general health with no remarkable medical conditions 4. BMI \<33 5. Provided informed consent
Exclusion criteria
1. Known history of liver or kidney disease 2. Use of prescription or non prescription medications, herbals, foods or chemicals known to be metabolized by or affecting CYP2B6 3. Females who are pregnant or nursing 4. Known history of drug or alcohol addiction (prior or present addiction or treatment for addiction) 5. 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Effects of CYP2B6 Genetic Variants on Ketamine Metabolism and Clearance by CYP2B6*6 Hetero or Homozygote Genotype. | up to 24 hours | Ketamine metabolism, measured as the plasma norketamine/ketamine AUC ratio in CYP2B6\*6 carriers (CYP2B6\*6 hetero or homozygotes) compared to the wild-type CYP2B6\*1/\*1 genotype Ketamine, norketamine, and dehydronorketamine concentrations in plasma and urine were determined by enantioselective HPLC tandem mass spectrometry, using solid phase extraction, based on a modification of a published method. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ketamine Arm- *1/*1 1.\*1/\*1- oral racemic ketamine 0.4 mg/kg
ketamine: 0.4 mg/kg oral racemic ketamine | 10 |
| Ketamine Arm - *1/*6 2\. \*1/\*6- oral racemic ketamine 0.4 mg/kg
ketamine: 0.4 mg/kg oral racemic ketamine | 10 |
| Ketamine Arm - *6/*6 3\. \*6/\*6- oral racemic ketamine 0.4 mg/kg
ketamine: 0.4 mg/kg oral racemic ketamine | 10 |
| Total | 30 |
Baseline characteristics
| Characteristic | Ketamine Arm - *1/*6 | Ketamine Arm - *6/*6 | Ketamine Arm- *1/*1 | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 10 Participants | 10 Participants | 30 Participants |
| Age, Continuous | 27 years STANDARD_DEVIATION 11 | 37 years STANDARD_DEVIATION 13 | 25 years STANDARD_DEVIATION 6 | 29 years STANDARD_DEVIATION 10 |
| Region of Enrollment United States | 10 participants | 10 participants | 10 participants | 10 participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 3 Participants | 11 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 7 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 10 | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 10 |
Outcome results
Primary
The Effects of CYP2B6 Genetic Variants on Ketamine Metabolism and Clearance by CYP2B6*6 Hetero or Homozygote Genotype.
Ketamine metabolism, measured as the plasma norketamine/ketamine AUC ratio in CYP2B6\*6 carriers (CYP2B6\*6 hetero or homozygotes) compared to the wild-type CYP2B6\*1/\*1 genotype Ketamine, norketamine, and dehydronorketamine concentrations in plasma and urine were determined by enantioselective HPLC tandem mass spectrometry, using solid phase extraction, based on a modification of a published method.
Time frame: up to 24 hours
Population: 3 genotype groups, metabolism measured for both R- and S-ketamine
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| R-ketamine *1/*1 | The Effects of CYP2B6 Genetic Variants on Ketamine Metabolism and Clearance by CYP2B6*6 Hetero or Homozygote Genotype. | 29 ng/ml*hr | Standard Deviation 10 |
| S-ketamine *1/*1 | The Effects of CYP2B6 Genetic Variants on Ketamine Metabolism and Clearance by CYP2B6*6 Hetero or Homozygote Genotype. | 21 ng/ml*hr | Standard Deviation 7 |
| R-ketamine *1/*6 | The Effects of CYP2B6 Genetic Variants on Ketamine Metabolism and Clearance by CYP2B6*6 Hetero or Homozygote Genotype. | 26 ng/ml*hr | Standard Deviation 11 |
| S-ketamine *1/*6 | The Effects of CYP2B6 Genetic Variants on Ketamine Metabolism and Clearance by CYP2B6*6 Hetero or Homozygote Genotype. | 19 ng/ml*hr | Standard Deviation 10 |
| R-ketamine *6/*6 | The Effects of CYP2B6 Genetic Variants on Ketamine Metabolism and Clearance by CYP2B6*6 Hetero or Homozygote Genotype. | 35 ng/ml*hr | Standard Deviation 21 |
| S-ketamine *6/*6 | The Effects of CYP2B6 Genetic Variants on Ketamine Metabolism and Clearance by CYP2B6*6 Hetero or Homozygote Genotype. | 23 ng/ml*hr | Standard Deviation 13 |
p-value: <0.05ANOVA