The Effects of BCRP Q141K on Allopurinol Pharmacokinetics and Dynamics

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.

NCT02956278 Chronic Gout Hyperuricemia

MeSH:Hyperuricemia

HPO:Hyperuricemia

2 Interventions

Name: Allopurinol

Name: Placebo

Purpose: Basic Science

Allocation: Non-Randomized

Parallel Assignment

There is one SNP

SNPs

1 rs2231142

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 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 Chronic Gout Hyperuricemia Hyperuricemia null

HPO Nodes

HPO:

HP:0002149: Hyperuricemia

Genes 40

UMOD SARS2 CLDN16 PRPS1 HNF1B EIF2AK3 SH2B1 HPRT1 UMOD MYC SLC37A4 MCFD2 LMAN1 ALDOB UMOD PFKM HPRT1 HMGCL HPRT1 ALDOB SLC37A4 PHKG2 HNF4A TNFRSF11B ACAT1 FBP1 HPRT1 HMGCL TNFRSF11A PHKA2 MUC1 PFKM ALMS1 HNF1B REN TNFRSF11B G6PC PPARG PPARG SEC61A1

Protein Mutations 1

Q141K

SNP 1

rs2231142