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Evaluation of ethnicity, gender, and OATP‐C genotypes as determinants of pravastatin disposition
Author(s) -
Ho R. H.,
Lee W.,
Mayo G.,
Dresser G. K.,
Bailey D. G.,
Kim R. B.
Publication year - 2004
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2003.11.248
Subject(s) - pravastatin , pharmacokinetics , organic anion transporting polypeptide , pharmacology , medicine , transporter , population , endocrinology , chemistry , cholesterol , biochemistry , environmental health , gene
Pravastatin is an HMG‐CoA reductase inhibitor (statin), widely used in the treatment of hypercholesterolemia. Previous studies have revealed that drug transporters are critical to the cellular uptake and elimination of pravastatin. The rate‐limiting step in the hepatic clearance of pravastatin appears to be cellular uptake, mediated by organic anion transporting polypeptide C (OATP‐C; SLC21A6 ), a liver‐specific uptake transporter with broad substrate specificities. Accordingly, pravastatin may be a useful in vivo probe of OATP‐C activity in humans. We have conducted a clinical study of pravastatin pharmacokinetics in a population of healthy Caucasian and African‐American volunteers after single dose (40 mg) administration of pravastatin. Preliminary (n=27) results show no significant differences in the area under the concentration‐time curve (AUC) from 0 to 3 hr between Caucasian and African‐American subjects (103.9 vs 106.4 ng*hr/ml). However, AUC values suggest gender‐dependent differences in pravastatin pharmacokinetics may exist. In addition, several single‐nucleotide polymorphisms (SNPs) previously identified by this laboratory to be important to OATP‐C function are being assessed for potential genotype:phenotype correlations. (see Table 1) Clinical Pharmacology & Therapeutics (2004) 75 , P66–P66; doi: 10.1016/j.clpt.2003.11.248Ethnicity Caucasian African‐AmGender Female (n=9) Male (n=11) Female (n=6) Male (n=1)avg SD avg SD avg SD avg SD AUC 0–3h (ng*hr/ml) 116.8 44.1 93.5 31.1 100.0 44.1 124.5 —