Brøsen K, Otton S V, Gram L F
Br J Clin Pharmacol. 1986 Jun;21(6):661-7. doi: 10.1111/j.1365-2125.1986.tb05231.x.
Polymorphic oxidation of the pharmacogenetic probe drug sparteine was investigated in 35 parents and 29 siblings of 20 unrelated poor metabolizer (PM) probands. Phenotyping was carried out on the basis of metabolic ratio (MR) = sparteine/dehydrosparteines in the 12 h urine. The distribution of MR was bimodal: 47 relatives (20 siblings and 27 parents) had MR ranging from 0.22-12 and were defined as extensive metabolizers (EM) whereas MR ranged from 20-340 in nine siblings and eight parents thus defined as PM. The 20 pedigrees confirmed that poor metabolism of sparteine is inherited as an autosomal recessive character. The mean recovery of dehydrosparteines (% of dose) was 27% in 23 positively identified drug free heterozygotes compared with 37% in unrelated EM (both genotypes) (P less than 0.05) previously phenotyped. Degrees of dominance of 73% and 77% were calculated on basis of log excretion of dehydrosparteines (% of dose in 12 h urine) and log MR, respectively.
对20名非亲缘关系的慢代谢（PM）先证者的35名父母及29名同胞进行了药物遗传学探针药物司巴丁的多态性氧化研究。基于12小时尿液中代谢比（MR）=司巴丁/脱氢司巴丁进行表型分析。MR的分布呈双峰型：47名亲属（20名同胞和27名父母）的MR范围为0.22 - 12，被定义为快代谢者（EM），而9名同胞和8名父母的MR范围为20 - 340，因此被定义为PM。20个家系证实司巴丁的慢代谢作为常染色体隐性性状遗传。在23名经阳性鉴定的无药物杂合子中，脱氢司巴丁的平均回收率（剂量的百分比）为27%，而之前表型分析的非亲缘EM（两种基因型）为37%（P < 0.05）。分别基于脱氢司巴丁的对数排泄（12小时尿液中剂量的百分比）和对数MR计算出显性度分别为73%和77%。
