Enantioselective metabolism of primaquine by human CYP2D6

Malaria Journal

Volumn 13, Issue 1, 2014, Pages

  Fasinu, Pius S ^a   Tekwani, Babu L ^a,b   Nanayakkara, N P Dhammika ^a   Avula, Bharathi ^a   Herath, H M T Bandara ^a   Wang, Yan Hong ^a   Adelli, Vijender R ^a   Elsohly, Mahmoud A ^a,b,c   Khan, Shabana I ^a,b   Khan, Ikhlas A ^a,b   Pybus, Brandon S ^d   Marcsisin, Sean R ^d   Reichard, Gregory A ^d   McChesney, James D ^e   Walker, Larry A ^a,b  

^a UNIVERSITY OF MISSISSIPPI   (United States)

^b UNIVERSITY OF MISSISSIPPI   (United States)

^c ElSohly Laboratories Incorporated   (United States)

^d WALTER REED ARMY INSTITUTE OF RESEARCH   (United States)

^e Ironstone Separations Inc   (United States)

Author keywords

CYP2D6; Metabolism; Orthoquinone; Primaquine enantiomers; Quinone imines; Ring hydroxylation

Indexed keywords

2 HYDROXYPRIMAQUINE; 3 HYDROXYPRIMAQUINE; 4 HYDROXYPRIMAQUINE; CARBON 13; CYTOCHROME P450 2D6; DRUG METABOLITE; PRIMAQUINE; UNCLASSIFIED DRUG; ANTIMALARIAL AGENT;

ARTICLE; CONTROLLED STUDY; DRUG METABOLISM; ENANTIOMER; ENANTIOSELECTIVITY; ISOTOPE LABELING; LIQUID CHROMATOGRAPHY; PHENOTYPE; QUANTITATIVE ANALYSIS; TANDEM MASS SPECTROMETRY; ULTRA PERFORMANCE LIQUID CHROMATOGRAPHY; CHEMISTRY; ENZYME SPECIFICITY; HUMAN; KINETICS; METABOLISM; PLASMODIUM VIVAX; STEREOISOMERISM;

ANTIMALARIALS; CHROMATOGRAPHY, LIQUID; CYTOCHROME P-450 CYP2D6; HUMANS; ISOTOPE LABELING; KINETICS; PLASMODIUM VIVAX; PRIMAQUINE; STEREOISOMERISM; SUBSTRATE SPECIFICITY; TANDEM MASS SPECTROMETRY;

EID: 84924286899     PISSN: None     EISSN: 14752875     Source Type: Journal    
DOI: 10.1186/1475-2875-13-507     Document Type: Article

References (37)

1. Tekwani BL, Walker LA: 8-aminoquinolines: future role as antiprotozoal drugs. Curr Opin Infect Dis 2006, 19:623-631.
2. Hill DR, Baird JK, Parise ME, Lewis LS, Ryan ET, Magill AJ: Primaquine: report from CDC expert meeting on malaria chemoprophylaxis. Am J Trop Med Hyg 2006, 75:402-415.
3. Vale N, Moreira R, Gomes P: Primaquine revisited six decades after its discovery. Eur J Med Chem 2009, 44:937-953.
4. Fernando D, Rodrigo C, Rajapakse S: Primaquine in vivax malaria: an update and review on management issues. Malar J 2011, 10:351.
5. WHO: Global Plan for Artemisinin Resistance Containment (GPARC). [http://www.wpro.who.int/mvp/artemisinin-resistance-containment-2011.pdf].
6. Beutler E, Duparc S: Glucose-6-phosphate dehydrogenase deficiency and antimalarial drug development. Am J Trop Med Hyg 2007, 77:779-789.
7. Uthman OA, Saunders R, Sinclair D, Graves P, Gelband H, Clarke A, Garner P: Safety of 8-aminoquinolines given to people with G6PD deficiency: protocol for systematic review of prospective studies. BMJ Open 2014, 4:e004664.
8. Tarlov AR, Brewer GL, Carson PE, Alving AS: Primaquine sensitivity. Arch Intern Med 1962, 109:209-234.
9. Avula B, Tekwani BL, Chaurasiya ND, Nanayakkara NP, Wang YH, Khan SI, Adelli VR, Sahu R, Elsohly MA, McChesney JD, Khan IA, Walker LA: Profiling primaquine metabolites in primary human hepatocytes using UHPLC-QTOF-MS with 13C stable isotope labeling. J Mass Spectrom 2013, 48:276-285.
10. Allahyari R, Strother A, Fraser IM, Verbiscar AJ: Synthesis of certain hydroxy analogs of the antimalarial drug primaquine and their in vitro methemoglobin-producing and glutathione-depleting activity in human erythrocytes. J Med Chem 1984, 27:407-410.
11. Link CM, Theoharides AD, Anders JC, Chung H, Canfield CJ: Structure-activity relationships of putative primaquine metabolites causing methemoglobin formation in canine hemolysates. Toxicol Appl Pharmacol 1985, 81:192-202.
12. Fletcher KA, Barton PF, Kelly JA: Studies on the mechanisms of oxidation in the erythrocyte by metabolites of primaquine. Biochem Pharmacol 1988, 37:2683-2690.
13. Vasquez-Vivar J, Augusto O: Hydroxylated metabolites of the antimalarial drug primaquine: oxidation and redox cycling. J Bio Chem 1992, 267:6848-6854.
14. Mihaly GW, Ward SA, Edwards G, Orme ML, Breckenridge AM: Pharmacokinetics of primaquine in man: identification of the carboxylic acid derivative as a major plasma metabolite. Br J Clin Pharmacol 1984, 17:441-446.
15. Peters W, Robinson BL: The activity of primaquine and its possible metabolites against rodent malaria. In Primaquine: Pharmacokinetics, Metabolism, Toxicity and Activity. Edited by Wernsdorfer WH, Trigg PI. Chichester: John Wiley; 1984:93-101.
16. Ganesan S, Tekwani BL, Sahu R, Tripathi LM, Walker LA: Cytochrome P450-dependent toxic effects of primaquine on human erythrocytes. Toxicol Appl Pharmacol 2009, 241:14-22.
17. Jin X, Pybus BS, Marcsisin SR, Logan T, Luong TL, Sousa J, Matlock N, Collazo V, Asher C, Carroll D, Olmeda R, Walker LA, Kozar MP, Melendez V: An LC-MS based study of the metabolic profile of primaquine, an 8-aminoquinoline antiparasitic drug, with an in vitro primary human hepatocyte culture model. Eur J Drug Metab Pharmacokinet 2014, 39:139-146.
18. Pybus BS, Sousa JC, Jin X, Ferguson JA, Christian RE, Barnhart R, Vuong C, Sciotti RJ, Reichard GA, Kozar MP, Walker LA, Ohrt C, Melendez V: CYP450 phenotyping and accurate mass identification of metabolites of the 8-aminoquinoline, anti-malarial drug primaquine. Malar J 2012, 11:259.
19. Bennett JW, Pybus BS, Yadava A, Tosh D, Sousa JC, McCarthy WF, Deye G, Melendez V, Ockenhouse CF: Primaquine failure and cytochrome P-450 2D6 in Plasmodium vivax malaria. N Engl J Med 2013, 369:1381-1382.
20. Marcsisin SR, Sousa JC, Reichard GA, Caridha D, Zeng Q, Roncal N, McNulty R, Careagabarja J, Sciotti RJ, Bennett JW, Zottig VE, Deye G, Li Q, Read L, Hickman M, Dhammika Nanayakkara NP, Walker LA, Smith B, Melendez V, Pybus BS: Tafenoquine and NPC-1161B require CYP 2D metabolism for anti-malarial activity: implications for the 8-aminoquinoline class of anti-malarial compounds. Malar J 2014, 13:2.
21. Pybus BS, Marcsisin SR, Jin X, Deye G, Sousa JC, Li Q, Caridha D, Zeng Q, Reichard GA, Ockenhouse C, Bennett J, Walker LA, Ohrt C, Melendez V: The metabolism of primaquine to its active metabolite is dependent on CYP 2D6. Malar J 2013, 12:212.
22. Schmidt LH, Alexander S, Allen L, Rasco J: Comparison of the curative antimalarial activities and toxicities of primaquine and its d and l isomers. Antimicrob Agents Chemother 1977, 12:51-60.
23. Nanayakkara ND, Tekwani BL, Herath HB, Sahu R, Gettayacamin M, Tungtaeng A, van Gessel Y, Baresel P, Wickham KS, Bartlett MS, Fronczek FR, Melendez V, Ohrt C, Reichard GA, McChesney JD, Rochford R, Walker LA: Scalable preparation and differential pharmacologic and toxicologic profiles of primaquine enantiomers. Antimicrob Agents Chemother 2014, 58:4737-4744.
24. Brocks DR, Mehvar R: Stereoselectivity in the pharmacodynamics and pharmacokinetics of the chiral antimalarial drugs. Clin Pharmacokinet 2003, 42:1359-1382.
25. Avula B, Khan SI, Tekwani BL, Nanayakkara NPD, McChesney JD, Walker LA, Khan IA: Analysis of primaquine and its metabolite carboxyprimaquine in biological samples: enantiomeric separation, method validation and quantification. Biomed Chromatogr 2011, 25:1010-1017.
26. Bortocan R, Bonato PS: Enantioselective analysis of primaquine and its metabolite carboxyprimaquine by capillary electrophoresis. Electrophoresis 2004, 25:2848-2853.
27. Herath HMT, McChesney JD, Walker LA, Nanayakkara NP: Synthesis of [13C6] primaquine. J Labelled Comp Radiopharm 2013, 56:341-343.
28. McChesney JD, Sarangan S: Synthesis of site specifically deuterated primaquines. II. N-alkyl deuterated primaquines. J Label Compd Radiopharm 1984, 21:293-298.
29. LaMontagne MP, Markovac A, Menke JR: Antimalarials. 10. Synthesis of 4-substituted primaquine analogs as candidate antimalarials. J Med Chem 1977, 20:1122-1127.
30. Bowman ZS, Morrow JD, Jollow DJ, McMillan DC: Primaquine-induced hemolytic anemia: role of membrane lipid peroxidation and cytoskeletal protein alterations in the hemotoxicity of 5-hydroxyprimaquine. J Pharmacol Exp Ther 2005, 314:838-845.
31. Wetter WP, Blanton CD: 8-(ω-Aminoalkylamino)quinolines as potential prophylactic antimalarials. J Med Chem 1974, 17:620-624.
32. Baker RH, Tinsley SW, Butler D, Riegel B: 3-Haloquinolines with substituents in the 6-and 8-positions. J Am Chem Soc 1950, 72:393-395.
33. Ganesan S, Chaurasiya ND, Sahu R, Walker LA, Tekwani BL: Understanding the mechanisms for metabolism-linked hemolytic toxicity of primaquine against glucose 6-phosphate dehydrogenase deficient human erythrocytes: evaluation of eryptotic pathway. Toxicology 2012, 294:54-60.
34. Bolchoz LJ, Budinsky RA, McMillan DC, Jollow DJ: Primaquine-induced hemolytic anemia: formation and hemotoxicity of the arylhydroxylamine metabolite 6-methoxy-8-hydroxylaminoquinoline. J Pharmacol Exp Ther 2001, 297:509-515.
35. Liu H, Tekwani BL, Nanayakkara ND, Walker LA, Doerksen RJ: Methemoglobin generation by 8-aminoquinolines: effect of substitution at 5-position of primaquine. Chem Res Toxicol 2013, 26:1801-1809.
36. Bowman ZS, Oatis JE, Whelan JL, Jollow DJ, McMillan DC: Primaquine-induced hemolytic anemia: susceptibility of normal versus glutathione-depleted rat erythrocytes to 5-hydroxyprimaquine. J Pharmacol Exp Ther 2004, 309:79-85.
37. Bowman ZS, Jollow DJ, McMillan DC: Primaquine-induced hemolytic anemia: role of splenic macrophages in the fate of 5-hydroxyprimaquine-treated rat erythrocytes. J Pharmacol Exp Ther 2005, 315:980-986.