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Developmental Pharmacogenetics of CYP2D6 in Chinese Children: Loratadine as a Substrate Drug.

ABSTRACT: Objective: The elucidation of CYP2D6 developmental pharmacogenetics in children has improved, however, these findings have been largely limited to studies of Caucasian children. Given the clear differences in CYP2D6 pharmacogenetic profiles in people of different ancestries, there remains an unmet need to better understand the developmental pharmacogenetics in populations of different ancestries. We sought to use loratadine as a substrate drug to evaluate the effects of ontogeny and pharmacogenetics on the developmental pattern of CYP2D6 in Chinese pediatric patients. Methods: Chinese children receiving loratadine treatment were enrolled in the present study. The metabolite-to-parent ratio (M/P ratio), defined as the molar ratio of desloratadine to loratadine of trough concentrations samples at steady-state condition, was used as a surrogate of CYP2D6 activity. Loratadine and desloratadine were determined by LC/MS/MS method. Variants of CYP2D6 were genotyped by polymerase chain reaction for CYP2D6 *4, *10, *41 and long polymerase chain reaction for CYP2D6 *5. Results: A total of 40 patients were available for final analysis. The mean age was 4.50 (range 0.50-9.00) years and the mean weight was 19.64 (range 7.00-42.00) kg. The M/P ratio was significantly lower in intermediate metabolizers (IMs) compared to normal metabolizers (NMs) (10.18 ± 7.97 vs. 18.80 ± 15.83, p = 0.03). Weight was also found to be significantly associated with M/P ratio (p = 0.03). Conclusion: The developmental pharmacogenetics of CYP2D6 in Chinese children was evaluated using loratadine as a substrate drug. This study emphasizes the importance of evaluating the developmental pharmacogenetics in populations of different ancestries.

SUBMITTER: Li Q

PROVIDER: S-EPMC8292113 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The Developmental Eye Movement (DEM) test is commonly used as a clinical visual-verbal ocular motor assessment tool to screen and diagnose reading problems at the onset. No established norm exists for using the DEM test with Mandarin Chinese-speaking Chinese children. This study aims to establish the normative values of the DEM test for the Mandarin Chinese-speaking population in China; it also aims to compare the values with three other published norms for English-, Spanish-, and Cantonese-speaking Chinese children. A random stratified sampling method was used to recruit children from eight kindergartens and eight primary schools in the main urban and suburban areas of Nanjing. A total of 1,425 Mandarin Chinese-speaking children aged 5 to 12 years took the DEM test in Mandarin Chinese. A digital recorder was used to record the process. All of the subjects completed a symptomatology survey, and their DEM scores were determined by a trained tester. The scores were computed using the formula in the DEM manual, except that the "vertical scores" were adjusted by taking the vertical errors into consideration. The results were compared with the three other published norms. In our subjects, a general decrease with age was observed for the four eye movement indexes: vertical score, adjusted horizontal score, ratio, and total error. For both the vertical and adjusted horizontal scores, the Mandarin Chinese-speaking children completed the tests much more quickly than the norms for English- and Spanish-speaking children. However, the same group completed the test slightly more slowly than the norms for Cantonese-speaking children. The differences in the means were significant (P<0.001) in all age groups. For several ages, the scores obtained in this study were significantly different from the reported scores of Cantonese-speaking Chinese children (P<0.005). Compared with English-speaking children, only the vertical score of the 6-year-old group, the vertical-horizontal time ratio of the 8-year-old group and the errors of 9-year-old group had no significant difference (P>0.05); compared with Spanish-speaking children, the scores were statistically significant (P<0.001) for the total error scores of the age groups, except the 6-, 9-, 10-, and 11-year-old age groups (P>0.05). DEM norms may be affected by differences in language, cultural, and educational systems among various ethnicities. The norms of the DEM test are proposed for use with Mandarin Chinese-speaking children in Nanjing and will be proposed for children throughout China.

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Developmental Pharmacogenetics of CYP2D6 in Chinese Children: Loratadine as a Substrate Drug.

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