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- W2021865732 abstract "Background Piroxicam (P), a widely prescribed NSAID, is eliminated by hydroxylation catalyzed by CYP2C9 enzyme, which is encoded by the polymorphic CYP2C9 gene. Methods Single oral doses (20 mg) of P were given to healthy, adult Brazilian volunteers with distinct CYP2C9 genotypes. The plasma P concentration and the P-induced changes in the activity of cyclooxygenase 1 (COX-1; ex-vivo formation of tromboxane B2 in blood) were measured from zero to 240h. Results P′s oral CL/F was significantly reduced, and both AUC and t1/2 were increased in carriers of variant alleles *2 and *3 in heterozygosis or homozygosis. There was no difference in these pharmacokinetic parameters between genotypes *1/*2 and *1/*3. Cmax was not affected by CYP2C9 genotype. (see Table) The AUC for the inhibitory effect of P on the activity of COX-1, expressed relative to the pre-dosing value (units.h) increased with the number of variant CYP2C9 alleles, from 110± 23 (*1/*1, n= 5) to 172± 44 (combined *1/*2 and *1/*3, n =12) and to 208 - 223 (combined *2/*2 and *3/*3, n =2). Conclusion We confirmed our previous observation with tenoxicam that both the variant alleles CYP2C9*2 and *3 significantly influence the pharmacokinetics of oxicam NSAIDs. We also show that both alleles *2 and *3 are associated with the intensity of the inhibitory effect of P on COX-1. Clinical Pharmacology & Therapeutics (2005) 77, P62–P62; doi: 10.1016/j.clpt.2004.12.127 Table 1. Pharmacokinetics of piroxicam in healthy Brazilians Parameter *1/*1 (n = 14) *1/*2 (n = 9) *1/*3 (n = 10) *2/*2 (n = 1) *2/*3 (n = 1) *3/*3 (n = 1) Cmax(mgL−1) 2.4 ± 0.7 2.2 ± 0.4 2.5 ± 0.4 1.6 1.9 2.6 AUC0-240h(mg.L−1) 136 ± 34 220 ± 77 221 ± 67 197 186 501 CL/F (L.h−1) 0.14 ± 0.03 0.09 ± 0.03 0.08 ± 0.02 0.09 0.07 0.01 t1/2 (h) 40.3 ± 9.8 72.8 ± 19.9 80.1 ± 24.7 94.6 118.5 674.1" @default.
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- W2021865732 date "2005-02-01" @default.
- W2021865732 modified "2023-09-25" @default.
- W2021865732 title "Influence of CYP2C9 genotypes on the pharmacokinetics and pharmacodynamics of piroxicam in Brazilians" @default.
- W2021865732 doi "https://doi.org/10.1016/j.clpt.2004.12.127" @default.
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