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• W2002294528 abstract "Aims We investigated flurbiprofen pharmacokinetics in 12 volunteers to develop a phenotypic trait measure that correlates with the fractional clearance to 4′‐hydroxyflurbiprofen. The effect of the CYP2C9 inhibitor fluconazole on flurbiprofen metabolism was also evaluated. Methods Flurbiprofen pharmacokinetics were evaluated before and after the first and seventh doses of fluconazole. The urinary recovery ratio was calculated as FLRR = 4′‐OHF/[4′‐OHF + F tot ] and the urinary metabolic ratio was calculated as FLMR = 4′‐OHF/ F tot , where 4′‐OHF and F tot represent total (conjugated and unconjugated) amounts recovered in urine. Results There was a statistically significant relationship between the 4′‐OHF formation clearance (4OHCLf) and both the 8‐h FLRR and the 8‐h FLMR with and without administration of fluconazole. The flurbiprofen apparent oral clearance (CL/ F ) was decreased by 53% [90% confidence interval (CI) −58, −48] and 64% (90% CI −69, −59), respectively, after administration of one and seven doses of fluconazole when compared with administration of flurbiprofen alone; similarly, the 4OHCLf decreased by 69% (90% CI −74, −64) and 78% (90% CI −83, −73), the 8‐h FLRR decreased by 35% (90% CI −41, −29) and 40% (90% CI −46, −35) and the 8‐h FLMR decreased by 61% (90% CI −65, −58) and 67% (90% CI −70, −63). The magnitude of decrease in CL/ F and 4OHCLf was greater after seven doses compared with after one dose of fluconazole ( P < 0.005). Conclusions This study provides strong evidence that both the 8‐h FLRR and the 8‐h FLMR are suitable phenotypic indices for CYP2C9 activity." @default.
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• W2002294528 date "2006-10-19" @default.
• W2002294528 modified "2023-10-17" @default.
• W2002294528 title "Evaluation of flurbiprofen urinary ratios as in vivo indices for CYP2C9 activity" @default.
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• W2002294528 doi "https://doi.org/10.1111/j.1365-2125.2006.02781.x" @default.
• W2002294528 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2203231" @default.
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