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PII‐23
Author(s) -
Oh H.,
Choi J.,
Lee M.,
Park K.
Publication year - 2006
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.2005.12.148
Subject(s) - cmax , pharmacokinetics , rosuvastatin , genotype , grapefruit juice , pharmacology , slco1b1 , organic anion transporting polypeptide , dosing , pravastatin , rosuvastatin calcium , chemistry , medicine , pharmacogenetics , cholesterol , biochemistry , transporter , gene
BACKGROUND To investigate the influence of the Organic Anion‐Transporting Polypeptide C(OATP‐C) genotype on rosuvastatin pharmacokinetics. METHODS 121 healthy Koreans were examined with regard to the OATP‐C*1b/*1b, OATP‐C*1b/*15, and OATP‐C*15/*15 genotype. The 3 genotypes were selected according to the study with 120 Japanese on pravastatin, where significant pharmacokinetic differences were observed among the 3 genotypes. Among 121 subjects, 13 subjects, 6 for *1b/*1b, 6 for *1b/*15, and 1 for *15/*15, were selected for the rosuvastatin pharmacokinetic study of a single oral dose of 10mg. Blood samples were collected at 0, 0.5, 1, 3, 5, 7, 10, 15, 24, 48, 72hr after dosing. Using a noncompartment method, area under concentration‐time (AUC), maximum concentration (Cmax), time to maximum concentration (Tmax) were calculated for the 3 genotypes. RESULTS AUC for *15/*15 was 201.4 ng·h/ml, whereas those for the other 2 genotypes were about a half (111±57 for *1b/*1b and 106±40 for *1b/*15, value as mean± SD) without significant difference each other (p=0.85). For *15/*15, Cmax was also twice as much, but Tmax was smallest. For lactone, 1b/*1b showed the highest value of AUC and Cmax among the 3 genotypes. CONCLUSIONS The results show that the genomic difference of OATP‐C can influence rosuvastatin pharmacokinetics. A study with more subjects would be necessary to further support our results. Influence on pharmacodynamics and other genetic variations such as MRP2 and BCRP may also need to be investigated. Clinical Pharmacology & Therapeutics (2005) 79 , P42–P42; doi: 10.1016/j.clpt.2005.12.148