The Effects of BCRP Q141K on Allopurinol Pharmacokinetics and Dynamics

Study Overview
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Brief Summary
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Subjects will undergo a placebo and allopurinol phase to better understand the effects of the reduced function BCRP Q141K variant on allopurinol pharmacokinetics and pharmacodynamics.

Official Title
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The Effects of BCRP Q141K on Allopurinol Pharmacokinetics and Dynamics

Conditions
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Chronic Gout, Hyperuricemia

Intervention / Treatment
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* Drug: Allopurinol
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: self-identified as Asian/European ancestry generally healthy with approved lab values for CBC,HFP,RFP, and uric acid Subjects with the ABCG2 genotype, homozygous, heterozygous or homozygous for the major allele of rs2231142 will be recruited Exclusion Criteria: vascular disease renal impairment medications/supplements that affect uric acid levels pregnant or lactating women prior history of allergic reaction to allopurinol or testing positive for HLA-B*5801 allele risk of urinary or gastric retention or narrow-angle glaucoma impaired hepatic function evidence of anemia evidence or diagnosis of congestive heart failure smokers subjects with a mutation other than rs2231142 in the ABCG2 genotype subjects taking hormonal contraceptives or other hormonal medications evidence of recreational drug use as determined by questionnaire

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: BCRP Q141K CC<br>Participants that are homozygous reference for BCRP Q141K receive at least one 300 mg dose of allopurinol followed by blood/urine collection for up to 72 hours post-dose. | Drug: Allopurinol<br> <br> * Other names: Aloprim;Other: Placebo<br>* lactose placebo pill<br>|
| Experimental: BCRP Q141K CA<br>Participants that are heterozygous for the BCRP Q141K allele receive at least one 300 mg dose of allopurinol, with blood/urine collections up to 72 hours post-dose. | Drug: Allopurinol<br> <br> * Other names: Aloprim;Other: Placebo<br>* lactose placebo pill<br>|
| Experimental: BCRP Q141K AA<br>Participants homozygous for the BCRP Q141K allele receive at least one 300 mg dose of allopurinol with blood/urine collection for up to 72 hours post-dose. | Drug: Allopurinol<br> <br> * Other names: Aloprim;Other: Placebo<br>* lactose placebo pill<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxypurinol Renal Clearance | Renal clearance as defined by amount excreted in 24 hours/AUC from 0-24 hours | 24 hours (Urine collected 0-4 hrs,4-8 hrs,8-10 hrs,10-24 hrs post-dose) | 
| Percent Change Uric Acid | Maximum percent change in uric acid after a single dose of allopurinol | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxypurinol AUC | Area under the concentration time curve from 0-24 hours following a single dose of allopurinol (i.e. Day 1 of both protocols) | 24 hours (Collections at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 24 hours post-dose) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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allopurinol