| Popis: |
Background/Aims The objective of this study was to investigate the effect of St. John's wort (SJW) administration on rosiglitazone metabolism in healthy subjects genotyped for CYP2C8 polymorphisms. Methods This fixed-sequence design study involved twenty-seven subjects sequentially selected with the following CYP2C8 genotypes: CYP2C8*1/*1 (n= 8), *1/*2 (n= 4), *1/*3 (n= 7), *1/*4 (n= 6), *2/*2 (n= 1), and *3/*3 (n= 1). The pharmacokinetics of single dose rosiglitazone (8 mg) was evaluated in the absence and presence of SJW 900 mg daily. Results SJW administration induced rosiglitazone metabolism as the area under the plasma concentration-time curve (AUC) decreased by 26%, from 3190± 641 μg×h/L to 2375± 537 μg×h/L (p< 0.0001, 90% Confidence Interval[CI] for mean ratio, 71% - 78%) and apparent oral clearance (CL/F) increased by 35% from 2.6± 0.6 L/h to 3.5± 0.7 L/h (p< 0.0001, 90% CI, 128% - 142%). The CYP2C8 genotype did not influence the magnitude of induction as the rosiglitazone AUC ratio (SJW/Control) was not significantly different (p= 0.96) between the subjects genotyped as CYP2C8*1/*1 and the heterozygous carriers of CYP2C8 variant alleles. Conclusions Administration of SJW significantly increases the CYP2C8 mediated clearance of rosiglitazone after single dose administration; the magnitude of induction by SJW is not influenced by CYP2C8 genotype. SJW use should be monitored when patients are administered CYP2C8 substrates. Clinical Pharmacology & Therapeutics (2005) 77, P35–P35; doi: 10.1016/j.clpt.2004.12.026 |
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