title: Cytochrome P450 2D6*10 genotype affects the pharmacokinetics of dimemorfan in healthy Chinese subjects.
abstract: This study aimed to investigate the effects of cytochrome P450 2D6*10 (100C > T, rs1065852) genotype on the pharmacokinetics of dimemorfan in healthy Chinese subjects. Data were evaluated from 24 subjects in two pharmacokinetic studies who received an oral dose of 40 mg of dimemorfan syrup (n = 12) or dimemorfan tablet (n = 12) after providing written informed consent and being divided into three groups: subjects with CYP2D6*10 CC (n = 5), CYP2D6*10 CT (n = 11) and CYP2D6*10 TT (n = 8). CC homozygotes and CT heterozygotes were defined to be C allele carriers. The CYP2D6*10 was genotyped by polymerase chain reaction-restriction fragment length polymorphism. Dimemorfan was measured by LC-MS/MS. There was significant difference in C max, AUC0-t , AUC0-inf, V z , and CL values of dimemorfan observed among the three CYP2D6*10 genotype groups (GLM, (a) P < 0.05, co-dominant model). CYP2D6*10 under the recessive model (CC + TC vs TT) was significantly associated with pharmacokinetics of dimemorfan ((c) P < 0.05). The C max values were significantly higher in subjects with CYP2D6*10 TT (8.06 ± 4.43 ng/mL) than CYP2D6*10 CC (3.41 ± 2.79 ng/mL), CYP2D6*10 CT (3.11 ± 2.47 ng/mL), so was AUC0-inf. V z /F and CL/F of subjects with CYP2D6*10 TT homozygotes were the lowest. We demonstrated that cytochrome P450 2D6*10 (100C > T, rs1065852) polymorphism can affect the pharmacokinetics of dimemorfan in humans, not dosage forms.
authors.affiliation: Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Pei
authors.affiliation: School of Pharmaceutical Science, Central South University, Changsha, China.
authors.forename: Jinfu
authors.initials: J
authors.lastname: Peng
authors.affiliation: Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.
authors.forename: Hongyi
authors.initials: H
authors.lastname: Tan
authors.affiliation: School of Pharmaceutical Science, Central South University, Changsha, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.affiliation: School of Pharmaceutical Science, Central South University, Changsha, China.
authors.forename: Xiding
authors.initials: X
authors.lastname: Yang
authors.affiliation: School of Pharmaceutical Science, Central South University, Changsha, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Shikun
authors.initials: S
authors.lastname: Liu
authors.affiliation: Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China. ygp9880@126.com.
authors.forename: Guoping
authors.initials: G
authors.lastname: Yang
mesh_terms: D000284:Administration, Oral; D044466:Asian People / Q000235:genetics*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005260:Female; D005838:Genotype; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D009019:Morphinans / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019999:Pharmaceutical Solutions / Q000008:administration & dosage / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D009019:Morphinans; D019999:Pharmaceutical Solutions; C012621:dimemorfan; D019389:Cytochrome P-450 CYP2D6
keywords: CYP2D6; Dimemorfan; Gene polymorphism; Pharmacokinetics; rs1065852