The role of Gilbert's syndrome and frequent NAT2 slow acetylation polymorphisms in the pharmacokinetics of retigabine

Pharmacogenomics Journal

Volumn 6, Issue 3, 2006, Pages 211-219

  Hermann, Robert ^a   Borlak, J ^b   Munzel, U ^c   Niebch, G ^c   Fuhr, U ^d   Maus, J ^c   Erb, K ^e  

^a ALTANA PHARMA AG   (Germany)

^b FRAUNHOFER INSTITUTE FOR TOXICOLOGY AND EXPERIMENTAL MEDICINE   (Germany)

^c Viatris Inc   (Germany)

^d UNIVERSITY OF COLOGNE   (Germany)

^e Clinphase Clinical Pharmacology Services   (Germany)

Author keywords

28 polymorphism; Genetic polymorphisms; Gilbert's syndrome; N acetyltransferase 2 slow acetylation polymorphisms; Pharmacokinetics; Retigabine; UGT1A1

Indexed keywords

ANTICONVULSIVE AGENT; ARYLAMINE ACETYLTRANSFERASE; AWD 21 360; BILIRUBIN; GLUCURONOSYLTRANSFERASE; GLUCURONOSYLTRANSFERASE 1A1; GLUCURONOSYLTRANSFERASE 1A4; GLUCURONOSYLTRANSFERASE 1A9; RETIGABINE; UNCLASSIFIED DRUG;

ADULT; ANALYSIS OF VARIANCE; AREA UNDER THE CURVE; ARTICLE; ASTHENIA; ATAXIA; BLOOD SAMPLING; CAUCASIAN; CLINICAL ARTICLE; CONCENTRATION LOSS; CONTROLLED STUDY; COORDINATION DISORDER; DIZZINESS; DOSE RESPONSE; DRUG ACETYLATION; DRUG ACTIVITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG GLUCURONIDATION; DRUG HALF LIFE; DRUG METABOLISM; DRUG SAFETY; DRUG STRUCTURE; DRUG TOLERABILITY; FATIGUE; FEMALE; GENETIC POLYMORPHISM; GENETIC SCREENING; GENETIC VARIABILITY; GENOTYPE PHENOTYPE CORRELATION; GILBERT DISEASE; HEADACHE; HETEROZYGOSITY; HUMAN; HUMAN CELL; HYPERBILIRUBINEMIA; MALE; MULTIPLE DRUG DOSE; NEUROLOGIC DISEASE; PARESTHESIA; PRIORITY JOURNAL; SINGLE DRUG DOSE; VERTIGO; VISUAL IMPAIRMENT;

ACETYLATION; ANALYSIS OF VARIANCE; ANTICONVULSANTS; ARYLAMINE N-ACETYLTRANSFERASE; CARBAMATES; GILBERT DISEASE; GLUCURONOSYLTRANSFERASE; HUMANS; PHENYLENEDIAMINES; POLYMORPHISM, GENETIC;

ATAXIA;

EID: 33744543460     PISSN: 1470269X     EISSN: 14731150     Source Type: Journal    
DOI: 10.1038/sj.tpj.6500359     Document Type: Article

References (45)

1. Borlak J, Thum T, Landt O, Erb K, Hermann R. Molecular diagnosis of a familial non haemolytic hyperbilirubinemia (Gilbert's syndrome) in healthy subjects. Hepatology 2000; 32: 792-795.
2. Bosma PJ, Chowdhury JR, Bakker C, Gantla S, de Boer A, Oostra BA et al. The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert's syndrome. N Engl J Med 1995; 333: 1171-1175.
3. Monaghan G, Ryan M, Seddon R, Hume R, Burchell B. Genetic variation in bilirubin UPD-glucuronosyltransferase gene promoter and Gilbert's syndrome. Lancet 1996; 347: 578-581.
4. Beutler E, Geleart T, Demina A. Racial variability in the UDP-glucuronyltransferase 1 (UGT1A1) promotor: A balanced polymorphism for regulation of bilirubin metabolism? Proc Natl Sci USA 1998; 95: 8170-8174.
5. Radu P, Atsmon J. Gilbert's syndrome - clinical and pharmacological implications. Isr Med Assoc J 2001; 3: 593-598.
6. Wasserman E, Myara A, Lokiec F, Goldwasser F, Trivin F, Mahjoubi M et al. Severe CPT-11 toxicity in patients with Gilbert's syndrome: Two case reports. Ann Oncol 1997; 8: 1049-1051.
7. Iyer L, Das S, Janisch L, Wen M, Ramirez J, Karrison T et al. UGT1A1*28 polymorphism as a determinant of irinotecan disposition and toxicity. Pharmacogenomics J 2002; 2: 43-47.
8. Spielberg SP. N-acetyltransferases: Pharmacogenetics and clinical consequences of polymorphic drug metabolism. J Pharmacokinet Biopharm 1996; 24: 509-519.
9. Ingelmann-Sundberg M. Pharmacogenetics: An opportunity for a safer and more efficient pharmacotherapy. J Int Med 2001; 250: 186-200.
10. Bjornsson TD, Wagner JA, Donahue SR, Harper D, Karim A, Khouri MS et al. A review and assessment of potential sources of ethnic differences in drug responsiveness. J Clin Pharmacol 2003; 43: 943-967.
11. Rostock A, Tober C, Rundfeldt C, Bartsch R, Engel J, Polymeropoulos EE et al. D-23129: A new anticonvulsant with a broad spectrum activity in animal models of epileptic seizures. Epilepsy Res 1996; 23: 211-223.
12. Tober C, Rostock A, Rundfeldt C, Bartsch R. D-23129: A potent anticonvulsant in the amygdala kindling model of complex partial seizures. Eur J Pharmacol 1996; 303: 163-169.
13. Armand V, Rundfeldt C, Heinemann U. Effects of retigbine (D-23129) on different patterns of epileptiform activity induced by 4-aminopyridine in rat entorhinal cortex hippocampal slices. Naunyn Schmiedebergs Arch Pharmacol 1999; 359: 33-39.
14. Armand V, Rundfeldt C, Heinemann U. Effects of retigabine (D-23129) on different patterns of epileptiform activity induced by low magnesium in rat entorhinal cortex hippocampal slices. Epilepsia 2000; 41: 28-33.
15. Wang HS, Pan Z, Shi W, Brown BS, Wymore RS, Cohen US et al. KCNQ2 and KCNQ3 potassium channel subunits: Molecular correlates of the M-channel. Science 1998; 282: 1890-1893.
16. Rundfeldt C, Netzer R. The novel anticonvulsant retigabine activates M-currents in Chinese hamster ovary-cells transfected with human KCNQ2/3 subunits. Neuroscie Lett 2000; 281: 73-76.
17. Main MJ, Cryan JE, Dupere JR, Cox B, Clare JJ, Burbidge SA et al. Modulation KCNQ2/3 potassium channels by the novel anticonvulsant retigabine. Mol Pharmacol 2000; 58: 253-262.
18. Wickenden AD, Yu WF, Zou AR, Jegla T, Wagoner PK. Retigabine, a novel anti-convulsant, enhances activation of KCNQ2/Q3 potassium channels. Mol Pharmacol 2000; 58: 591-600.
19. Wickenden AD, Zou AR, Wagoner PK, Jegla T. Characterization of KCNQ5/Q3 potassium channels expressed in mammalian cells. Br J Pharmacol 2001; 132: 381-384.
20. 2+ channels. Arzneimittelforsch/Drug Res 2000; 50: 1063-1070.
21. Kapetanovic IM, Rundfeldt C. A new anticonvulsant compound. CNS Drug Rev 1996; 2: 308-321.
22. Hermann R, Schneider E, Menth M, Knebel N, Ferron GM, Borlak J et al. Retigabine. In: Bialer M, Johannessen S, Kupferberg H, Levy R, Loiseau P, Perucca E (eds). Progress report on new antiepileptic drugs: A summary of the Sixth Eilat Conference (EILAT VI); Epilepsy Res 2002; 51: 36-38.
23. McNeilly PJ, Torchin CD, Anderson LW, Kapetanovic IM, Kupferberg HJ, Strong JM. In vitro glucuronidation of D-23129, a new anticonvulsant, by human liver microsomes and liver slices. Xenobiotica 1997; 27: 431-441.
24. Hempel R, Schupke H, McNeilly PJ, Heinecke K, Kronbach C, Grunwald C et al. Metabolism of retigabine (D-23129), a novel anticonvulsant. Drug Metab Dispos 1999; 27: 613-622.
25. Hiller A, Nguyen N, Strassburg CP, Li Q, Jainta H, Pechstein B et al. Retigabine N-glucuronidation and its potential role in enterohepatic circulation. Drug Metab Dispos 1999; 27: 605-612.
26. Borlak J, Gasparic A, Locher M, Schupke H, Hermann R. N-glucuronidation of the antiepileptic drug retigabine: Results from studies with human volunteers, heterologous expressed human UGTs, human liver, kidney and liver microsomal membranes of Crigler-Najjar Type II. Metabolism 2005; 54, in press.
27. Hermann R, Ferron GM, Erb K, Knebel N, Ruus P, Paul J et al. Effects of age and sex on the disposition of retigabine. Clin Pharmacol Ther 2003; 73: 61-70.
28. Hermann R, Knebel N, Niebch G, Paul J, Richards L, Borlak J et al. Pharmacokinetic interaction between retigabine and lamotrigine in healthy subjects. Eur J Clin Pharmacol 2003; 58: 795-802.
29. Ferron GM, Paul J, Fruncillo R, Richards L, Knebel N, Getsy J et al. Multiple-dose, linear, dose-proportional pharmacokinetics of retigabine in healthy volunteers. J Clin Pharmacol 2002; 42: 175-182.
30. Benowitz NL, Perez-Stable EJ, Fong I, Modin G, Herrera B, Jacob III P. Ethnic differences in N-glucuronidation of nicotine and cotinine. J Pharmacol Exp Ther 1999; 291: 1196-1203.
31. Skarke C, Schmidt H, Geisslinger G, Darimont J, Loetsch J. Pharmacokinetics of morphine are not altered in subjects with Gilbert's syndrome. Br J Clin Pharmacol 2003; 56: 228-231.
32. Holthe M, Klepstad P, Zahlsen K, Borchgrevink PC, Hagen L, Dale O et al. Morphine glucuronide-to-morphine plasma ratios are unaffected by the UGT2B7 H268Y and UGT1A1 28 polymorphisms in cancer patients on chronic morphine therapy. Eur J Clin Pharmacol 2002; 58: 353-356.
33. Esteban A, Perez-Mateo M. Heterogeneity of paracetamol metabolism in Gilbert's syndrome. Eur J Drug Metab Pharmacokinet 1999; 24: 9-13.
34. Court MH, Duan SX, von Moltke LL, Greenblatt DJ, Patten CJ, Miners JO et al. Interindividual variability in acetaminophen glucuronidation by human liver microsomes: Identification of relevant acetaminophen UDP-glucuronyltransferase isoforms. J Pharmacol Exp Ther 2001; 299: 998-1006.
35. Herman RJ, Chaudhary A, Szakacs CB. Disposition of lorazepam in Gilbert's syndrome: Effects of fasting, feeding, and enterohepatic circulation. J Clin Pharmacol 1994; 34: 978-984.
36. Iyer L, King CD, Roy SK, Whitington PR, Tephly TR, Coffmann B et al. Genetic predisposition to the metabolism of irinotecan: Role of UGT1A1 in the glucuronidation of its active metabolite (SN-38) in human liver microsomes. J Clin Invest 1998; 101: 847-854.
37. Iyer L, Hall D, Das S, Mortell MA, Ramirez J, Kim S et al. Phenotype-genotype correlation of in vitro SN-38 (active metabolite of irinotecan) and bilirubin glucuronidation in human liver tissue with UGT1A1 promotor polymorphism. Clin Pharmacol Ther 1999; 65: 576-582.
38. Martin-Escudero JC, Duenas-Laita A, Perez-Castrillon JL, Herrreros-Fernandez V. Olanzapine toxicity in unconjugated hyperbilirubinemia (Gilbert's syndrome). Br J Psychol 2003; 182: 267.
39. Danoff TM, Campbell DA, McCarthy LC, Lewis KF, Repasch MH, Saunders AM et al. A Gilbert's syndrome UGT1A1 variant confers susceptibility to tranilast-induced hyperbilirubinemia. Pharmacogenomics J 2004; 4: 49-53.
40. Zucker SD, Qin X, Rouster SD, Yu F, Green RM, Keshavan P et al. Mechanism of indinavir-induced hyperbilirubinemia. Proc Natl Acad Sci USA 2001; 98: 12671-12676.
41. Jetter A, Kinzig-Schippers M, Illauer M, Hermann R, Erb K, Borlak J et al. Phenotyping of N-acetyltransferase type 2 by caffeine from uncontrolled dietary exposure. Eur J Clin Pharmacol 2004; 60: 17-21.
42. Tang BK, Kadar D, Qian L, Iriah J, Yip J, Kalow W. Caffeine as a metabolic probe: Validation of its use for acetylator phenotyping. Clin Pharmacol Ther 1991; 49: 648-657.
43. Knebel NG, Grieb S, Leisenheimer S, Locher M. Determination of retigabine and its acetyl metabolite in biological matrices by on-line solid-phase extraction (column switching) liquid chromatography with tandem mass spectrometry. J Chromatogr B Biomed Sci Appl 2000; 748: 97-111.
44. Rowland M, Tozer TN. Clinical Pharmacokinetics: Concepts and Applications, 3rd edn. Williams & Wilkins: Baltimore, MD, 1995.
45. FUNCALC. Collection of functions for noncompartmental Excel-based pharmacokinetic evaluations. Version 1.23, ASTA Medica, Feb 28, 2001.