UGT1A6 genotype-related pharmacokinetics of deferiprone (L1) in healthy volunteers

British Journal of Clinical Pharmacology

Volumn 65, Issue 6, 2008, Pages 908-916

  Limenta, Lie Michael George ^a   Jirasomprasert, Totsapol ^a   Tankanitlert, Jeeranut ^b   Svasti, Saovaros ^c   Wilairat, Prapin ^a   Chantharaksri, Udom ^a   Fucharoen, Suthat ^c   Morales, Noppawan Phumala ^a  

^a Mahidol University   (Thailand)

^b PHRAMONGKUTKLAO HOSPITAL   (Thailand)

^c MAHIDOL UNIVERSITY   (Thailand)

Author keywords

Deferiprone; Iron; L1; Pharmacokinetics; UGT1A6

Indexed keywords

DEFERIPRONE; DEFERIPRONE GLUCURONIDE; DRUG METABOLITE; FERRITIN;

ADULT; ALLELE; ARTICLE; CLINICAL TRIAL; DRUG BLOOD LEVEL; DRUG DISTRIBUTION; DRUG EXCRETION; DRUG METABOLISM; DRUG URINE LEVEL; FEMALE; FERRITIN BLOOD LEVEL; GENE; GENETIC POLYMORPHISM; GENOTYPE; HUMAN; HUMAN EXPERIMENT; MALE; NORMAL HUMAN; PRIORITY JOURNAL; SEX DIFFERENCE; SINGLE DRUG DOSE; SINGLE NUCLEOTIDE POLYMORPHISM; UGT1A6 GENE; VOLUNTEER;

ADULT; FEMALE; GENOTYPE; GLUCURONOSYLTRANSFERASE; HUMANS; IRON; IRON CHELATING AGENTS; MALE; POLYMORPHISM, GENETIC; PYRIDONES; SEX FACTORS; STATISTICS AS TOPIC;

EID: 43549106286     PISSN: 03065251     EISSN: 13652125     Source Type: Journal    
DOI: 10.1111/j.1365-2125.2008.03103.x     Document Type: Article

References (31)

1. Vreugdenhil G, Swaak AJ, Kontoghiorghes GJ, van Eijk HG. Efficacy and safety of oral iron chelator L1 in anaemic rheumatoid arthritis patients. Lancet 1989 2: 1398 9.
2. Mohanty D, Ghosh K, Pathare AV, Karnad D. Deferiprone (L1) as an adjuvant therapy for Plasmodium falciparum malaria. Indian J Med Res 2002 115: 17 21.
3. Singh S, Epemolu RO, Dobbin PS, Tilbrook GS, Ellis BL, Damani LA, Hider RC. Urinary metabolic profiles in human and rat of 1,2-dimethyl- and 1,2-diethyl-substituted 3-hydroxypyridin-4-ones. Drug Metab Dispos 1992 20: 256 61.
4. Hoffbrand AV, Al-Refaie F, Davis B, Siritanakatkul N, Jackson BF, Cochrane J, Prescott E, Wonke B. Long-term trial of deferiprone in 51 transfusion-dependent iron overloaded patients. Blood 1998 91: 295 300.
5. Olivieri NF. Randomized trial of deferiprone (L1) and deferoxamine (DFO) in thalassemia major. Blood 1996 88: 651a.
6. Diav-Citrin O, Atanackovic G, Koren G. An investigation into variability in the therapeutic response to deferiprone in patients with thalassemia major. Ther Drug Monit 1999 21: 74 81.
7. Haverfield EV, Weatherall DJ, Graber AY, Ramirez J, Ratain MJ. Pharmacogenomics of deferiprone metabolism. Blood 2005 106: Abstract 2703.
8. Ciotti M, Marrone A, Potter C, Owens IS. Genetic polymorphism in the human UGT1A6 (planar phenol) UDP-glucuronosyltransferase: pharmacological implications. Pharmacogenetics 1997 7: 485 95.
9. Saeki M, Saito Y, Jinno H, Sai K, Kaniwa N, Ozawa S, Komamura K, Kotake T, Morishita H, Kamakura S, Kitakaze M, Tomoike H, Shirao K, Minami H, Ohtsu A, Yoshida T, Saijo N, Kamatani N, Sawada J. Genetic polymorphisms of UGT1A6 in a Japanese population. Drug Metab Pharmacokinet 2005 20: 85 90.
10. Lampe JW, Bigler J, Horner NK, Potter JD. UDP-glucuronosyltransferase (UGT1A1*28 and UGT1A6*2) polymorphisms in Caucasians and Asians: relationships to serum bilirubin concentrations. Pharmacogenetics 1999 9: 341 9.
11. Stobie S, Tyberg J, Matsui D, Fernandes D, Klein J, Olivieri N, Bentur Y, Koren G. Comparison of the pharmacokinetics of 1,2-dimethyl-3-hydroxypyrid-4- one (L1) in healthy volunteers, with and without co-administration of ferrous sulfate, to thalassemia patients. Int J Clin Pharmacol Ther Toxicol 1993 31: 602 5.
12. Nagar S, Zalatoris JJ, Blanchard RL. Human UGT1A6 pharmacogenetics: identification of a novel SNP, characterization of allele frequencies and functional analysis of recombinant allozymes in human liver tissue and in cultured cells. Pharmacogenetics 2004 14: 487 99.
13. Tankanitlert J, Morales NP, Howard TA, Fucharoen P, Ware RE, Fucharoen S, Chantharaksri U. Effects of combined UDP-glucuronosyltransferase (UGT) 1A1*28 and 1A6*2 on paracetamol pharmacokinetics in beta-thalassemia/HbE. Pharmacology 2006 79: 97 103.
14. International Committee for Standardization in Hematology (ICSH). Recommendations for measurement of serum iron in human blood. Br J Haematol 1978 38: 291 4.
15. Bock KW, Schrenk D, Forster A, Griese EU, Morike K, Brockmeier D, Eichelbaum M. The influence of environmental and genetic factors on CYP2D6, CYP1A2 and UDP-glucuronosyltransferases in man using sparteine, caffeine, and paracetamol as probes. Pharmacogenetics 1994 4: 209 18.
16. Greenblatt DJ, Divoll M, Harmatz JS, Shader RI. Oxazepam kinetics: effects of age and sex. J Pharmacol Exp Ther 1980 215: 86 91.
17. Court MH, Duan SX, von Moltke LL, Greenblatt DJ, Patten CJ, Miners JO, Mackenzie PI. Interindividual variability in acetaminophen glucuronidation by human liver microsomes: identification of relevant acetaminophen UDP-glucuronosyltransferase isoforms. J Pharmacol Exp Ther 2001 299: 998 1006.
18. Krishnaswamy S, Hao Q, Al-Rohaimi A, Hesse LM, von Moltke LL, Greenblatt DJ, Court MH. UDP glucuronosyltransferase (UGT) 1A6 pharmacogenetics. II. Functional impact of the three most common nonsynonymous UGT1A6 polymorphisms (S7A, T181A, and R184S). J Pharmacol Exp Ther 2005 313: 1340 6.
19. Bigler J, Whitton J, Lampe JW, Fosdick L, Bostick RM, Potter JD. CYP2C9 and UGT1A6 genotypes modulate the protective effect of aspirin on colon adenoma risk. Cancer Res 2001 61: 3566 9.
20. Chan AT, Tranah GJ, Giovannucci EL, Hunter DJ, Fuchs CS. Genetic variants in the UGT1A6 enzyme, aspirin use, and the risk of colorectal adenoma. J Natl Cancer Inst 2005 97: 457 60.
21. Hubner RA, Muir KR, Liu JF, Logan RF, Grainge M, Armitage N, Shepherd V, Popat S, Houlston RS. Genetic variants of UGT1A6 influence risk of colorectal adenoma recurrence. Clin Cancer Res 2006 12: 6585 9.
22. Hoyes KP, Porter JB. Subcellular distribution of desferrioxamine and hydroxypyridin-4-one chelators in K562 cells affects chelation of intracellular iron pools. Br J Haematol 1993 85: 393 400.
23. Kontoghiorghes GJ, Neocleous K, Kolnagou A. Benefits and risks of deferiprone in iron overload in thalassaemia and other conditions: comparison of epidemiological and therapeutic aspects with deferoxamine. Drug Saf 2003 26: 553 84.
24. Finch CA, Bellotti V, Stray S, Lipschitz DA, Cook JD, Pippard MJ, Huebers HA. Plasma ferritin determination as a diagnostic tool. West J Med 1986 145: 657 63.
25. Miners JO, Knights KM, Houston JB, Mackenzie PI. In vitro-in vivo correlation for drugs and other compounds eliminated by glucuronidation in humans: pitfalls and promises. Biochem Pharmacol 2006 71: 1531 9.
26. Radominska-Pandya A, Czernik PJ, Little JM, Battaglia E, Mackenzie PI. Structural and functional studies of UDP-glucuronosyltransferases. Drug Metab Rev 1999 31: 817 99.
27. Uchaipichat V, Mackenzie PI, Guo XH, Gardner-Stephen D, Galetin A, Houston JB, Miners JO. Human UDP-glucuronosyltransferases: isoform selectivity and kinetics of 4-methylumbelliferone and 1-naphthol glucuronidation, effects of organic solvents, and inhibition by diclofenac and probenecid. Drug Metab Dispos 2004 32: 413 23.
28. Senay C, Jedlitschky G, Terrier N, Burchell B, Magdalou J, Fournel-Gigleux S. The importance of cysteine 126 in the human liver UDP-glucuronosyltransferase UGT1A6. Biochim Biophys Acta 2002 1597: 90 6.
29. Ouzzine M, Antonio L, Burchell B, Netter P, Fournel-Gigleux S, Magdalou J. Importance of histidine residues for the function of the human liver UDP-glucuronosyltransferase UGT1A6: evidence for the catalytic role of histidine 370. Mol Pharmacol 2000 58: 1609 15.
30. Krishnaswamy S, Hao Q, Al-Rohaimi A, Hesse LM, von Moltke LL, Greenblatt DJ, Court MH. UDP glucuronosyltransferase (UGT) 1A6 pharmacogenetics. I. Identification of polymorphisms in the 5′-regulatory and exon 1 regions, and association with human liver UGT1A6 gene expression and glucuronidation. J Pharmacol Exp Ther 2005 313: 1331 9.
31. Bock KW, Kohle C. UDP-glucuronosyltransferase 1A6: structural, functional, and regulatory aspects. Methods Enzymol 2005 400: 57 75.