Summary
Sparteine oxidation, which exhibits genetic polymorphism in various Caucasian populations, was studied in 154 unrelated Ghanaian subjects. Mean total urinary recovery of sparteine and 2- and 5-dehydrosparteines (56.6±16.6% of the dose) was not different from Caucasians. In contrast to Caucasians, amongst whom 6.3 to 9% of the population are poor metabolizers (PM), no PM subject was observed in the Ghanaian population sample. The data appear to indicate allelic differences between Caucasians and Ghanaians in the gene encoding the synthesis of the P-450 isozyme involved in polymorphic sparteine oxidation.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Boobis AR, Murray S, Kahn GC, Robertz GM, Davies DS (1983) Substrate specificity of the form of cytochrome P-450 catalyzing the 4-hydroxylation of debrisoquine in man. Mol Pharmacol 23: 474–481
Dengler HJ, Eichelbaum M (1977) Polymorphismen und Defekte des Arzneimittelstoffwechsels als Ursache toxischer Reaktionen. Arzneimittelforsch 27: 1836–1844
Dick B, Küpfer A, Molnar J, Braunschweig S, Preisig R (1982) Hydroxylierungsdefekt für Medikamente (Typus Debrisoquin) in der Stichprobe der Schweizer Bevölkerung. Schweiz Med Wochenschr 112: 1061–1065
Eichelbaum M, Spannbrucker N, Dengler HJ (1978) A probably genetic defect of the metabolism of sparteine. In: Gorrod JW (ed) Biological oxidation of nitrogen. Elsevier/North-Holland Biomedical Press
Eichelbaum M, Spannbrucker N, Steincke B, Dengler HJ (1979) Defective N-oxidation of sparteine in man — A new pharmacogenetic defect. Eur J Clin Pharmacol 16: 183–187
Eichelbaum M (1982a) Defective oxidation of drugs: Kinetic and therapeutic implications. Clin Pharmacokinet 7: 1–22
Eichelbaum M, Bertilsson L, Säwe J, Zekorn C (1982b) Polymorphic oxidation of sparteine and debrisoquine. Related pharmacogenetic entities. Clin Pharmacol Ther 31: 184–186
Eichelbaum M (1984) Polymorphic drug oxidation in humans. Fed Proc 43: 98–102
Fugura K, Aida K, Koiso Y, Okuda S (1973) Studies on microbial transformation. XXVI. Microbial oxidation of (-)-sparteine. Chem Pharm Bull [Tokyo] 21 [1]: 231–234
Guengerich FP (1979) Isolation and purification of cytochrome P-450 and the existence of multiple forms. Pharmacol Ther 6: 99–121
Hammer W, Sjöqvist F (1967) Plasma levels of monomethylated tricyclic antidepressants during treatment with imipramine-like compounds. Life Sci 6: 1895–1903
Idle JR, Smith RL (1979) Polymorphism of drug oxidation at carbon centers of drugs and their clinical significance. Drug Metab Rev 9: 301–317
Inaba T, Otton SV, Kalow W (1980) Deficient metabolism of debrisoquine and sparteine. Clin Pharmacol Ther 27: 547–549
Inaba T, Otton SV, Kalow W (1981) Debrisoquine hydroxylation capacity: problems of assessment in two populations. Clin Pharmacol Ther 29: 2, 218–223
Inaba T, Vinks A, Otton SV, Kalow W (1983) Comparative pharmacogenetics of sparteine and debrisoquine. Clin Pharmacol Ther 33: 394–399
Islam SI, Idle JR, Smith RL (1980) The polymorphic 4-hydroxylation of debrisoquine in a Saudi arab population. Xenobiotica 10: 819–825
Kalow W (1982) Ethnic differences in drug metabolism. Clin Pharmacokinet 7: 373–400
Kotake WN, Funae Y (1980) High performance liquid chromatography technique for resolving multiple forms of hepatic membrane — bound cytochrome P-450. Proc Natl Acad Sci USA 77: 6473–6475
Küpfer A, Dick B, Preisig R (1981) Polymorphic mephenytoin hydroxylation in man: a new phenotype in the genetic control of hepatic drug metabolism. Hepatology 1: 524
Kutt H, Wolk M, Schermann R, McDowell F (1964) Insufficient parahydroxylation as a cause of diphenylhydantoin toxicity. Neurology 14: 542–548
Maghoub A, Idle JR, Dring LG, Lancaster R, Smith RL (1979) The polymorphic hydroxylation of debrisoquine in man. Lancet 2: 584–586
Maghoub A, Idle JR, Smith RL (1979) A population and a familial study of the defective alicyclic hydroxylation of debrisoquine among Egyptians. Xenobiotica 9: 51–56
Nebert DW (1979) Multiple forms of inducible drug — metabolizing enzymes — A reasonable mechanism by which any organism can cope with adversity. Mol Cell Biochem 27: 27–46
Otton SV, Inaba T, Mahon WA, Kalow W (1981) In vitro metabolism of sparteine by human liver: competitive inhibition by debrisoquine. Can J Physiol Pharmacol 60: 102–105
Price-Evans DA, Maghoub A, Sloan TP, Idle JR, Smith RL (1980) A family and population study of the genetic polymorphism of debrisoquine oxidation in a white British population. J Med Genet 17: 102–105
Price-Evans DA, Harmer D, Downham DY, Whigley EJ, Idel JR, Ritchie J, Smith RL (1983) The genetic control of sparteine and debrisoquine metabolism in man (with novel methods of analysing bimodal distributions). J Med Genet 20: 321–329
Sjöqvist F, Hammer W, Ideström C-M, Lind M, Tuck D, Asberg M (1968) Plasma level of monomethylated tricyclic antidepressants and side-effects in man. Excerpta Medica Int Congr Ser 145: 246–257
Ullrich V, Kremer P (1977) Multiple forms of cytochrome P-450 in the microsomal monooxygenase system. Arch Toxicol 39: 41–50
Vinks A, Inaba T, Otton SV, Kalow W (1982) Sparteine metabolism in Canadian Caucasians. Clin Pharmacol Ther 31: 23–29
Wang PP, Beaune P, Kaminsky LS, Dannan GA, Kadlubar FF, Larrey D, Guengerich FP (1983) Purification and characterization of six cytochrome P-450 isozymes from human liver microsomes. Biochemistry 22: 5375–5383
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Eichelbaum, M., Woolhouse, N.M. Inter-ethnic difference in sparteine oxidation among Ghanaians and Germans. Eur J Clin Pharmacol 28, 79–83 (1985). https://doi.org/10.1007/BF00635712
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00635712