Genetic aspects of the polymodally distributed sulphoxidation of S-carboxymethyl-L-cysteine in man

Abstract

Interindividual variation in the sulphoxidation of S-carboxymethyl-L-cysteine (750 mg p.o.) was investigated in 200 healthy volunteers. Nearly a 100-fold difference was observed between individuals with respect to the amount of sulphoxide metabolites detected in their 0-8 h urine (0.6 to 59.1% recovery). Such a difference was shown to be reproducible over several months in 40 subjects who spanned the entire range of capacities. Cumulative plots and maximum likelihood analysis of the distribution indicated that a bimodal model was most probable. Analysis of pedigree data obtained from 12 families suggested a genetic effect with overlying environmental influences.

PIP: Interindividual variation in the sulphoxidation potential of S-carboxymethyl-L-cysteine was examine in 200 healthy white volunteers, and the role of various factors influencing it was assessed. The volunteers ranged in age from 18 to 53 years, with a mean of 22.6, and in body weight from 45 to 93 kg, with a mean of 63.5. None consumed more than moderate amounts of alcohol, but 43 smoked. 44 of the 110 females used oral contraceptives (OCs). The families of 12 subjects also participated. Each volunteer took 750 mg of the drug following a light breakfast. Urine was collected for 8 hours following administration and samples were quantitatively analyzed for the parent compound and its metabolites. The value obtained for the percentage recovery present as sulphoxide metabolites was found to be reproducible in 40 subjects who underwent repeat tests over several months. Statistical analysis showed that no significant association existed between the percentage of the administered dose excreted as sulphoxide metabolites and the total recovery, age, or body weight of the subjects. The 44 women taking OCs produced significantly lower 0-8 hour urine volumes and excreted more of the total dose as sulphoxide metabolites than did women not on OCs, although individual exceptions occurred. The total drug recoveries obtained for both groups were not statistically different. The variation between individuals in the amount of sulphoxide metabolites excreted ranged from .6% to 59.1%, virtually a 100-fold difference. Cumulative plot and maximum likelihood analysis of the distribution indicated that a biomodial model was most probable. Results of further study of the families of 12 subjects to determine whether the phenomenon of impaired sulphoxidation was under genetic influence suggested both a genetic effect and possibly a family environmental effect, although the latter could have been due to nonrandom sampling.