| Effects of NAT2 polymorphism on SASP pharmacokinetics in Chinese population. | |
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MedLine Citation:
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PMID: 19560446 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Sulfasalazine (SASP) pharmacologic actions are widely applied in clinical therapy. The role of N-Acetyltransferase 2 (NAT2) in the pharmacokinetics of SASP and its metabolites has not been clarified. We investigated the effects of genetic polymorphism of NAT2 on pharmacokinetic profiles of SASP and its two metabolites, sulfapyridine (SP) and N-acetylsufapyridine (AcSP). METHODS: Eighteen subjects were recruited and divided into 3 groups by NAT2 genotype: wild type (w/w), heterozygous variant (w/m), homozygous variant (m/m). After taking 1000mg SASP tablets, the plasma concentrations of SASP, SP and AcSP were measured with HPLC method and pharmacokinetic parameters were calculated by using the computing program 3P97. RESULTS: The AUC(0)(-)(72) and Cmax of SP in m/m subjects were significantly higher than those in w/m and w/w subjects, with the values of 172.57+/-49.42, 103.38+/-39.85, 71.37+/-17.52mg h/l, and 9.65+/-2.34, 6.10+/-1.79, 4.55+/-1.38mg/l, respectively. In contrast, the AUC(0)(-)(72) of AcSP was significantly lower in m/m subjects. The Cmax of AcSP in w/w, w/m and m/m subjects was 12.67+/-3.32, 9.07+/-2.29 and 4.22+/-0.93mg/l, respectively, with significant differences among groups. However, there was no significant difference in any pharmacokinetic parameter of SASP among groups. CONCLUSION: Different NAT2 genotypes, leading to functional heterogeneity of NAT2, may affect pharmacokinetics of SP and AcSP. Therefore, genotyping NAT2 gene before administration would be important in SASP therapy. |
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Authors:
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Jing-Jing Ma; Cun-Gang Liu; Jin-Heng Li; Xiao-Mei Cao; Sheng-Li Sun; Xuan Yao |
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Publication Detail:
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Type: Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't Date: 2009-06-26 |
Journal Detail:
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Title: Clinica chimica acta; international journal of clinical chemistry Volume: 407 ISSN: 1873-3492 ISO Abbreviation: Clin. Chim. Acta Publication Date: 2009 Sep |
Date Detail:
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Created Date: 2009-08-03 Completed Date: 2009-10-22 Revised Date: 2010-09-08 |
Medline Journal Info:
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Nlm Unique ID: 1302422 Medline TA: Clin Chim Acta Country: Netherlands |
Other Details:
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Languages: eng Pagination: 30-5 Citation Subset: IM |
Affiliation:
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Department of Clinical Pharmacology, Jinling Hospital, Clinical School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, PR China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Oral Arylamine N-Acetyltransferase / genetics* Asian Continental Ancestry Group / genetics* Calibration China Feasibility Studies Humans Male Polymorphism, Genetic* Quality Control Sulfapyridine / analogs & derivatives, blood, metabolism, pharmacokinetics Sulfasalazine / administration & dosage, blood, metabolism, pharmacokinetics* Young Adult |
| Chemical | |
Reg. No./Substance:
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144-83-2/Sulfapyridine; 19077-98-6/N-acetylsulfapyridine; 599-79-1/Sulfasalazine; EC 2.3.1.5/Arylamine N-Acetyltransferase; EC 2.3.1.5/NAT2 protein, human |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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