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Defective N-oxidation of Sparteine in Man: a New Pharmacogenetic Defect

Overview
Journal Eur J Clin Pharmacol
Specialty Pharmacology
Date 1979 Sep 1
PMID 499318
Citations 169
Authors
M Eichelbaum
N Spannbrucker
B Steincke
H J DENGLER
Affiliations
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Abstract

Sparteine, an antiarrhythmic and oxytocic drug, is metabolised by N1-oxidation. The sparteine-N1-oxide rearranges with loss of water to 2- and 5-dehydrosparteine. 18 (i.e., 5%) out of 360 subjects were unable to metabolise the drug. These persons, who were designated as nonmetabolisers, excreted almost 100% of the administered dose in urine as unchanged drug. The defective metabolism of sparteine was found to have a genetic basis. Sparteine-N1-oxidation appears to be determined by two allelic genes at a single locus where nonmetabolisers are homozygous for an autosomal recessive gene.

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References
1.
Eichelbaum M, Spannbrucker N, DENGLER H . Influence of the defective metabolism of sparteine on its pharmacokinetics. Eur J Clin Pharmacol. 1979; 16(3):189-94. DOI: 10.1007/BF00562060. View
2.
Binnig F . [The chemistry of sparteins]. Arzneimittelforschung. 1974; 24(5):752-3. View
3.
GOEDDE H . [Pharmacogenetics: variability of drug effects and metabolic reactions]. Internist (Berl). 1974; 15(1):27-39. View
4.
SHAHIDI N . Acetophenetidin-induced methemoglobinemia. Ann N Y Acad Sci. 1968; 151(2):822-32. DOI: 10.1111/j.1749-6632.1968.tb48266.x. View
5.
BONICKE R, REIF W . [Enzymatic inactivation of isonicotinic acid hydrizide in human and animal organism]. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1953; 220(4):321-3. View