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No significant effect of ABCB1 haplotypes on the pharmacokinetics of fluvastatin, pravastatin, lovastatin, and rosuvastatin
Author(s) -
Keskitalo Jenni E.,
Kurkinen Kaisa J.,
Neuvonen Mikko,
Backman Janne T.,
Neuvonen Pertti J.,
Niemi Mikko
Publication year - 2009
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2009.03440.x
Subject(s) - pravastatin , fluvastatin , lovastatin , rosuvastatin , pharmacokinetics , statin , pharmacology , hydroxymethylglutaryl coa reductase , medicine , atorvastatin , cholesterol , chemistry , endocrinology , hmg coa reductase , simvastatin , reductase , biochemistry , enzyme
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • ABCB1 genotype affects the pharmacokinetics and cholesterol‐lowering effects of simvastatin and atorvastatin. • The cholesterol‐lowering effect of fluvastatin has been associated with ABCB1 genotype, and pravastatin, lovastatin, lovastatin acid, and rosuvastatin are substrates of ABCB1. • However, it is not known whether ABCB1 genotype affects the pharmacokinetics of fluvastatin, pravastatin, lovastatin, or rosuvastatin. WHAT THIS STUDY ADDS • ABCB1 c.1236C‐c.2677G‐c.3435C and c.1236T‐c.2677T‐c.3435T haplotypes have no significant effects on the pharmacokinetics of fluvastatin, pravastatin, lovastatin, or rosuvastatin. AIMS This study aimed to investigate possible effects of ABCB1 genotype on fluvastatin, pravastatin, lovastatin, and rosuvastatin pharmacokinetics. METHODS In a fixed‐order crossover study, 10 healthy volunteers with the ABCB1 c.1236C/C‐c.2677G/G‐c.3435C/C (CGC/CGC) genotype and 10 with the c.1236T/T‐c.2677T/T‐c.3435T/T (TTT/TTT) genotype ingested a single 20‐mg dose of fluvastatin, pravastatin, lovastatin, and rosuvastatin. Plasma fluvastatin, pravastatin, and lovastatin concentrations were measured up to 12 h and plasma and urine rosuvastatin concentrations up to 48 and 24 h, respectively. RESULTS The ABCB1 genotype had no significant effect on the pharmacokinetics of any of the investigated statins. The geometric mean ratio (95% confidence interval) of the area under the plasma concentration–time curve from 0 h to infinity (AUC 0–∞ ) in participants with the TTT/TTT genotype to that in those with the CGC/CGC genotype was 0.96 (0.77, 1.20; P = 0.737) for fluvastatin, 0.92 (0.53, 1.62; P = 0.772) for pravastatin, 0.83 (0.36, 1.90; P = 0.644) for lovastatin, 1.25 (0.72, 2.17; P = 0.400) for lovastatin acid, and 1.10 (0.73, 1.65; P = 0.626) for rosuvastatin. The AUC 0–∞ of lovastatin acid correlated significantly with that of rosuvastatin ( r = 0.570, P = 0.009), but none of the other AUC 0–∞ pairs showed a significant correlation. CONCLUSIONS These data suggest that the ABCB1 c.1236C‐c.2677G‐c.3435C and c.1236T‐c.2677T‐c.3435T haplotypes play no significant role in the interindividual variability in the pharmacokinetics of fluvastatin, pravastatin, lovastatin, and rosuvastatin.