N-acetylation and Debrisoquine Hydroxylation Polymorphisms in Patients with Gilbert's Syndrome

Overview

Journal Br J Clin Pharmacol

Specialty Pharmacology

Date 1991 Oct 1

PMID 1958441

Authors

W Siegmund

J D Fengler

G Franke

M Zschiesche

O Eike

E Eike

P Meisel

R Wulkow

Affiliations

Soon will be listed here.

Abstract

1. N-acetylation and debrisoquine hydroxylation phenotypes were determined in 54 patients with Gilbert's syndrome and in 247 (sulphamethazine) and 76 (debrisoquine) non-related healthy volunteers. 2. Forty (74.1%) of the patients and 135 (54.7%) of the healthy volunteers were slow acetylators (chi 2 = 6.87). In the patients, the cumulative urinary excretion of sulphamethazine up to 6 h (Ae(0,6)) was significantly lower. No differences in the frequency of debrisoquine poor metabolizers were observed: Gilbert's syndrome 5/54 (9.3%), healthy volunteers 5/76 (6.6%). The metabolic ratios were similar in both groups as well as the urinary recoveries of debrisoquine and its 4-hydroxy metabolite. 3. Gilbert's syndrome seems to be related in some way to N-acetylation but not to the debrisoquine hydroxylation polymorphism.

References

Caporaso N, Hayes R, Dosemeci M, Hoover R, Ayesh R, Hetzel M . Lung cancer risk, occupational exposure, and the debrisoquine metabolic phenotype. Cancer Res. 1989; 49(13):3675-9. View

BARNIVILLE H, MISK R . Urinary glucuronic acid excretion in liver disease and the effect of a salicylamide load. Br Med J. 1959; 1(5118):337-40. PMC: 1992464. DOI: 10.1136/bmj.1.5118.337. View

Evans D . N-acetyltransferase. Pharmacol Ther. 1989; 42(2):157-234. DOI: 10.1016/0163-7258(89)90036-3. View

Sieg A, Stiehl A, Raedsch R, Ullrich D, Messmer B, KOMMERELL B . Gilbert's syndrome: diagnosis by typical serum bilirubin pattern. Clin Chim Acta. 1986; 154(1):41-7. DOI: 10.1016/0009-8981(86)90086-0. View

Blanckaert N . Analysis of bilirubin and bilirubin mono- and di-conjugates. Determination of their relative amounts in biological samples. Biochem J. 1980; 185(1):115-28. PMC: 1161276. DOI: 10.1042/bj1850115. View

Ayesh R, Idle J, Ritchie J, Crothers M, Hetzel M . Metabolic oxidation phenotypes as markers for susceptibility to lung cancer. Nature. 1984; 312(5990):169-70. DOI: 10.1038/312169a0. View

Ishizaki T, Chiba K, Sasaki T . Antipyrine clearance in patients with Gilbert's syndrome. Eur J Clin Pharmacol. 1984; 27(3):297-302. DOI: 10.1007/BF00542163. View

Billing B, Williams R, RICHARDS T . DEFECTS IN HEPATIC TRANSPORT OF BILIRUBIN IN CONGENITAL HYPERBILIRUBINAEMIA: AN ANALYSIS OF PLASMA BILIRUBIN DISAPPEARANCE CURVES. Clin Sci. 1964; 27:245-57. View

Ullrich D, Sieg A, Blume R, Bock K, Schroter W, BIRCHER J . Normal pathways for glucuronidation, sulphation and oxidation of paracetamol in Gilbert's syndrome. Eur J Clin Invest. 1987; 17(3):237-40. DOI: 10.1111/j.1365-2362.1987.tb01242.x. View

10.

Black M, Billing B . Hepatic bilirubin udp-glucuronyl transferase activity in liver disease and gilbert's syndrome. N Engl J Med. 1969; 280(23):1266-71. DOI: 10.1056/NEJM196906052802303. View

11.

Stiehl A . [Hyperbilirubinemia in liver diseases]. Fortschr Med. 1982; 100(18):842-5. View

12.

Martin J, Vierling J, Wolkoff A, Scharschmidt B, Vergalla J, WAGGONER J . Abnormal hepatic transport of indocyanine green in Gilbert's syndrome. Gastroenterology. 1976; 70(3):385-91. View

13.

FOULK W, BUTT H, OWEN Jr C, WHITCOMB Jr F, MASON H . Constitutional hepatic dysfunction (Gilbert's disease): its natural history and related syndromes. Medicine (Baltimore). 1959; 38(1):25-46. View

14.

Ohkubo H, Okuda K, Iida S . A constitutional unconjugated hyperbilirubinemia combined with indocyanine green intolerance: a new functional disorder?. Hepatology. 1981; 1(4):319-24. DOI: 10.1002/hep.1840010407. View

15.

Schmid R, HAMMAKER L . Glucuronide formation in patients with constitutional hepatic dysfunction (Gilbert's disease). N Engl J Med. 1959; 260(26):1310-4. DOI: 10.1056/NEJM195906252602603. View

16.

Preisig D, BIRCHER J, Preisig R . [Positive diagnosis of Gilbert syndrome. Retrospective analysis of 59 cases with special reference to the nicotinic acid test]. Schweiz Med Wochenschr. 1982; 112(33):1122-9. View

17.

Roots I, Drakoulis N, Ploch M, Heinemeyer G, Loddenkemper R, Minks T . Debrisoquine hydroxylation phenotype, acetylation phenotype, and ABO blood groups as genetic host factors of lung cancer risk. Klin Wochenschr. 1988; 66 Suppl 11:87-97. View

18.

Arias I . Chronic unconjugated hyperbilirubinemia without overt signs of hemolysis in adolescents and adults. J Clin Invest. 1962; 41:2233-45. PMC: 291158. DOI: 10.1172/JCI104682. View

19.

METGE W, OWEN Jr C, FOULK W, HOFFMANN 2nd H . BILIRUBIN GLUCURONYL TRANSFERASE ACTIVITY IN LIVER DISEASE. J Lab Clin Med. 1964; 64:89-98. View

20.

Zschiesche M, Hanke W, Siegmund W, Franke G, Wilke A . Oxidation phenotyping with debrisoquine in Germany (East). Pharmazie. 1990; 45(12):920-1. View