Genetic study of amobarbital elimination based on its kinetics in twins

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Abstract
Following the intravenous administration of }25 mg amobarbital sodium in 7 pairs (if dizygotic and 7 pairs of monozygotic twins, the time-course of plasma concentrations was observed. The number of detectable compartments varied from subject to subject but was consistently} or 2 or 3 within a given individual. The terminal slope of the semilogarithmic concentration-time plot (corresponding to biologic half-life of 22.8 hr) did not represent the elimination rate constant even in persons with apparently single-compartmental characteristics. The redistribution of amobarbital was rapid in comparison with its elimination. The rate of the latter (characterized by kel = 0.05} hr−1, plasma clearance = 37.7 ml/min} could be closely idelltified with the rate of metabolism. The twin data showed that genetic control was exerted on kinetic parameters characterizing the rate of amobarbital elimination and, therefore, the rate of its metabolism. Correlation analysis suggested that this control was independent of size factors, which were themselves substantially heritahle. The genetic analysis of twin data included, in addition to intraclass correlations and Holzinger's H factors, newly developed lower (and upper) bounds of the broad-sense heritability. In pharmacogenetic studies, assessment (it model-independent kinetic parameters, such as plasma clearance with or without adjustment for body weight, is recommended.