Intra-individual variability and influence of urine collection period on dextromethorphan metabolic ratios in healthy subjects
Intra-individual variability and influence of urine collection period on dextromethorphan metabolic ratios in healthy subjects
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DOI：
10.1111/j.1472-8206.1999.tb00011.x
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发表时间：
1999-01-01
影响因子：
2.9
通讯作者：
Tuma, I
中科院分区：
文献类型：
--
作者：
Chládek, J;Zimová, G;Tuma, I
本研究的目的是评价健康志愿者中美沙芬（DM）代谢率（MR）的个体内变异性，并比较给药后0-4、0-8和0-24 h采集的尿液中的MR。对10名健康男性和4名女性高加索人（10名DM的强代谢型（EM）和4名DM的弱代谢型（PM））单次口服27.5 mg氢溴酸DM后，获得DM与右啡烷（MR 1）和DM与甲氧基吗啡喃（MR 2）的尿摩尔比，以探测CYP 2D 6和CYP 3A的活性。分别7名Ehl和1名PM在2个月内另外3次接受DM治疗。对于7种EM，在3次尿液采集中获得的MR的个体内变异性（CVw）范围为11 - 93%（MRI）和8 - 77%（MR 2）。通过双因素方差分析分别估计的4、8和24 h尿液的平均CVw分别达到MRI的58、57和44%，以及50。MR 2分别为42%和31%。对于所有14名受试者，24小时尿液中获得的对数转换比值MR 1）与8小时尿液（r（s）= 0.967，P < 0.0001）或4小时尿液（r（s）= 0.946，P < 0.0001）中的比值高度相关。对数转换的MR 2之间的相关性较弱（24 h vs. 8 h：r（s）= 0.829，P
The aim of the study was to evaluate intra-individual variability in metabolic ratios (MRs) of dextromethorphan (DM) in healthy volunteers and to compare the MRs in urine collected 0-4, 0-8 and 0-24 h post-dose. Urinary molar ratios of DM to dextrorphan (MR 1) and of DM to methoxymorphinan (MR2) were obtained after a single oral 27.5 mg dose of DM hydrobromide to ten healthy male and four female Caucasians (ten extensive metabalizers (EM) and four poor metabolizers (PM) of DM) to probe activities of CYP2D6 and CYP3A. respectively. Seven Ehl and one PM received DM on three additional occasions within 2 months. For the seven EM, the intraindividual variability (CVw) in the MRs obtained in the three urine collections ranged from 11 to 93% (MRI) and from 8 to 77% (MR2). The mean CVw estimated separately for the 4, 8 and 24 h urines by two-way analysis of variance reached 58, 57 and 44% for the MRI and 50. 42 and 31% for the MR2, respectively. For all 14 subjects, the log-transformed ratios MR1) obtained in the 24 h urines were highly correlated with those in either the 8 h (r, = 0.967, P < 0.0001) or 4 h urines (r(s) = 0.946, P < 0.0001). Correlation between the log transformed MR2s were weaker (24 h vs. 8 h: r(s) = 0.829, P