title: Effects of the Chinese herbal formula "Zuojin Pill" on the pharmacokinetics of dextromethorphan in healthy Chinese volunteers with CYP2D6*10 genotype.
abstract: OBJECTIVE
  Zuojin Pill has been shown to inhibit the cytochrome P450 (CYP) 2D6 isoenzyme in vitro. In Chinese individuals, CYP 2D6*10 is the most common allele with reduced enzyme activity. In this study, we investigated the pharmacokinetic interaction between Zuojin Pill and the sensitive CYP2D6 probe dextromethorphan in healthy Chinese volunteers with CYP2D6*10 genotype.
  
  
  METHODS
  A pharmacokinetics interaction study was carried out in three groups with CYP2D6*1/*1 (n = 6), CYP2D6*1/*10 (n = 6), and CYP2D6*10/*10 (n = 6) genotypes. Each participant received a single oral dose of dextromethorphan (15 mg) followed by Zuojin Pill (3 g twice daily) for 7 days, and received 3 g Zuojin Pill with 15 mg dextromethorphan in the last day. Blood samples (0-24 h) and urine samples (0-12 h) were collected at baseline and after the administration of Zuojin Pill, and the samples' concentration of dextromethorphan and its main metabolite dextrorphan was determined.
  
  
  RESULTS
  Compared to baseline values, co-administration of Zuojin Pill (3 g twice daily) for 7 days increased the AUC0-24 of dextromethorphan [mean (90 % CI)] by 3.00-fold (2.49∼3.61) and 1.71-fold (1.42∼2.06), and decreased oral clearance(CL/F) by 0.27-fold (0.2-0.40) and 0.57-fold (0.48-0.67) in the participants with CYP2D6*1/*1 and CYP2D6*1/*10 genotypes, respectively. In contrast, no significant change was observed in these pharmacokinetic parameters of the participants with CYP2D6*10/*10 genotype.
  
  
  CONCLUSIONS
  These data demonstrated that administration of Zuojin Pill inhibited moderately CYP2D6-mediated metabolism of dextromethorphan in healthy volunteers. The inhibitory influence of CYP2D6 was greater in CYP2D6*1/*1 and CYP2D6*1/*10 groups than CYP2D6 *10/*10 group.
authors.affiliation: Laboratory of Clinical Pharmacokinetics, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, No. 528 Zhangheng road, Shanghai, 201203, People's Republic of China. furong_qiu@126.com.
authors.forename: Furong
authors.initials: F
authors.lastname: Qiu
authors.affiliation: Laboratory of Clinical Pharmacokinetics, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, No. 528 Zhangheng road, Shanghai, 201203, People's Republic of China.
authors.forename: Songcan
authors.initials: S
authors.lastname: Liu
authors.affiliation: Laboratory of Clinical Pharmacokinetics, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, No. 528 Zhangheng road, Shanghai, 201203, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Miao
authors.affiliation: Laboratory of Clinical Pharmacokinetics, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, No. 528 Zhangheng road, Shanghai, 201203, People's Republic of China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Laboratory of Clinical Pharmacokinetics, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, No. 528 Zhangheng road, Shanghai, 201203, People's Republic of China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Laboratory of Clinical Pharmacokinetics, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, No. 528 Zhangheng road, Shanghai, 201203, People's Republic of China.
authors.forename: TongFang
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Laboratory of Clinical Pharmacokinetics, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, No. 528 Zhangheng road, Shanghai, 201203, People's Republic of China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Laboratory of Clinical Pharmacokinetics, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, No. 528 Zhangheng road, Shanghai, 201203, People's Republic of China. jiangjiansg@126.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Jiang
mesh_terms: D000328:Adult; D000996:Antitussive Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D044466:Asian People / Q000235:genetics; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D003915:Dextromethorphan / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005260:Female; D005838:Genotype; D064368:Healthy Volunteers; D041743:Herb-Drug Interactions; D006801:Humans; D008297:Male; D055815:Young Adult
chemical_list: D000996:Antitussive Agents; D004365:Drugs, Chinese Herbal; C545320:zuojin; D003915:Dextromethorphan; D019389:Cytochrome P-450 CYP2D6
keywords: CYP2D6*10 genotype; Dextromethorphan; Drug interaction; Pharmacokinetics; Zuojin Pill