کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2486504 | 1114384 | 2010 | 17 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Oral Sulfasalazine as a Clinical BCRP Probe Substrate: Pharmacokinetic Effects of Genetic Variation (C421A) and Pantoprazole Coadministration
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
This study evaluated the utility of oral sulfasalazine as a probe substrate for Breast Cancer Resistance Protein (BCRP; ABCG2) activity by assessing the impact of genetic variation or coadministration of an inhibitor (pantoprazole) on plasma and urine pharmacokinetics of sulfasalazine and metabolites. Thirty-six healthy male subjects prescreened for ABCG2 421CC (reference activity), CA, and AA (lower activity) genotypes (Nâ=â12 each) received a single 500âmg oral dose of enteric coated sulfasalazine alone, with 40âmg pantoprazole, or with 40âmg famotidine (gastrointestinal pH control) in a 3-period, single fixed sequence, crossover design. No significant difference in sulfasalazine or metabolite pharmacokinetics in 421AA or CA compared to 421CC subjects was found; however, high inter-subject variability was observed. Geometric mean (95% CI) sulfasalazine plasma AUC(0-â) values were 32.1 (13.2, 78.1), 16.8 (7.15, 39.6) and 62.7 (33.4, 118) µgâh/mL, and Cmax were 4.01 (1.62, 9.92), 1.70 (0.66, 4.40), and 6.86 (3.61, 13.0) µg/mL for CC, CA, and AA subjects, respectively. Pantoprazole and famotidine did not affect sulfasalazine pharmacokinetics in any genotypic cohort. These results suggest that the pharmacokinetics of oral, enteric-coated 500âmg sulfasalazine are not sufficiently sensitive to ABCG2 genetic variation or inhibitors to be useful as a clinical probe substrate of BCRP activity. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:1046-1062, 2010
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 99, Issue 2, February 2010, Pages 1046-1062
Journal: Journal of Pharmaceutical Sciences - Volume 99, Issue 2, February 2010, Pages 1046-1062
نویسندگان
Kimberly K. Adkison, Soniya S. Vaidya, Daniel Y. Lee, Seok Hwee Koo, Linghui Li, Amar A. Mehta, Annette S. Gross, Joseph W. Polli, Joan E. Humphreys, Yu Lou, Edmund J.D. Lee,