ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
World Health Organization, 2015. World Malaria Report. Geneva, Switzerland: World Health Organization.
-
2.
World Health Organization, 2010. Guidelines for the Treatment of Malaria. Geneva, Switzerland: World Health Organization.
-
3.
Hill DR, Baird JK, Parise ME, Lewis LS, Ryan ET, Magill AJ, 2006. Primaquine: report from CDC expert meeting on malaria chemoprophylaxis I. Am J Trop Med Hyg 65: 402–415.
-
4.
Vale N, Moreira R, Gomes P, 2009. Primaquine revised six decades after its discovery. Eur J Med Chem 44: 937–953.
-
5.
Baird JK, Hoffman SL, 2004. Primaquine therapy for malaria. Clin Infect Dis 39: 1336–1345.
-
6.
Robert W, Taylor J, White NJ, 2004. Antimalarials drug toxicity: a review. Drug Saf 27: 25–61.
-
7.
Hsiech HS, Jaffe ER, 1975. The metabolism of methemoglobin in human erythrocytes. Surgenor DMN, ed. The Red Blood Cell. New York, NY: Academic Press II, 799–824.
-
8.
Kiese M, 1974. Methemoglobinemia: A Comprehensive Treatise. Cleveland, OH: CRC Press.
-
9.
Carmona-Fonseca J, Álvarez G, Maestre A, 2009. Methemoglobinemia and adverse events in Plasmodium vivax malaria patients associated with high doses of primaquine treatment. Am J Trop Med Hyg 80: 188–193.
-
10.
Greaves J, Evans DAP, Fletcher KA, 1980. Urinary primaquine excretion and red cell methaemoglobin levels in man following a primaquine: chloroquine regimen. Br J Clin Pharmacol 10: 293–295.
-
11.
Cohen RJ, Sachs JR, Wicker DJ, Conrad ME, 1968. Methemoglobinemia provoked by malarial chemoprophylaxis in Vietnam. N Engl J Med 279: 1127–1131.
-
12.
Mihaly GW, Ward SA, Edwards G, Orme ML, Breckenridge AM, 1984. Pharmacokinetics of primaquine in man: identification of the carboxylic acid derivative as a major plasma metabolite. Br J Clin Pharmacol 17: 441–446.
-
13.
Ganesan S, Tekwani BL, Sahu R, Tripathi LM, Walker LA, 2009. Cytochrome P450-dependent toxic effects of primaquine on human erythrocytes. Toxicol Appl Pharmacol 241: 14–22.
-
14.
Bennett JW, Pybus BS, Yadava A, Tosh D, Sousa JC, McCarthy WF, Deye G, Melendez V, Ockenhouse CF, 2013. Primaquine failure and cytochrome P-450 2D6 in Plasmodium vivax malaria. N Engl J Med 369: 1381–1382.
-
15.
Potter BM, Xie LH, Vuong C, Zhang J, Zhang P, Duan D, Luong TL, Bandara Herath HM, Dhammika Nanayakkara NP, Tekwani BL, Walker LA, Nolan CK, Sciotti RJ, Zottig VE, Smith PL, Paris RM, Read LT, Li Q, Pybus BS, Sousa JC, Reichard GA, Marcsisin SR, 2015. Differential CYP 2D6 metabolism alters primaquine pharmacokinetics. Antimicrob Agents Chemother 59: 2380–2387.
-
16.
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, 2013. The metabolism of primaquine to its active metabolite is dependent on CYP 2D6. Malar J 12: 212–221.
-
17.
Ma MK, Woo MH, McLeod HL, 2002. Genetic basis of drug metabolism. Am J Health Syst Pharm 59: 2061–2069.
-
18.
Bertilsson L, 1995. Geographical/interracial differences in polymorphic drug oxidation. Current state of knowledge of cytochromes P450 (CYP) 2D6 and 2C19. Clin Pharmacokinet 29: 192–209.
-
19.
Meibohm B, Beierle I, Derendorf H, 2002. How important are gender differences in pharmacokinetics? Clin Pharmacokinet 41: 329–342.
-
20.
Gandhi M, Aweeka F, Greenblatt RM, Blaschke TF, 2004. Sex differences in pharmacokinetics and pharmacodynamics. Annu Rev Pharmacol Toxicol 44: 499–523.
-
21.
Oliveira-Ferreira J, Lacerda MV, Brasil P, Ladislau JL, Tauil PL, Daniel Ribeiro CT, 2010. Malaria in Brazil: an overview. Malar J 9: 115–132.
-
22.
Dua VK, Kar EK, Sarina R, Sharma VP, 1996. High-performance liquid chromatographic determination of primaquine and carboxyprimaquine concentrations in plasma and blood cells in Plasmodium vivax malaria cases following chronic dosage with primaquine. J Chromatogr B Biomed Sci Appl 657: 93–98.
-
23.
Hegesh E, Grener N, Cohen OS, Bochkousky R, Shuval HI, 1972. A sensitive micromethod for the determination of methemoglobin in blood. Clin Chim Acta 30: 679–683.
-
24.
Ward SA, Mihaly GW, Edwards G, Looareesuwan S, Phillips RE, Chanthavanich P, Warrell DA, Orme ML, Breckenridge AM, 1985. Pharmacokinetics of primaquine in man. II. Comparison of acute vs chronic dosage in Thai subjects. Br J Clin Pharmacol 19: 751–755.
-
25.
Bangchang KN, Songsaeng W, Thanavibul A, Chroenlarp P, Karbwang J, 1994. Pharmacokinetics of primaquine in G6PD deficient and G6PD normal patients with vivax malaria. Trans R Soc Trop Med Hyg 88: 220–222.
-
26.
Pukrittayakamee S, Tarning J, Jittamala P, Charunwatthana P, Lawpoolsri S, Lee SJ, Hanpithakpong W, Hanboonkunupakarn B, Day NP, Ashley EA, White NJ, 2014. Pharmacokinetic interactions between primaquine and chloroquine. Antimicrob Agents Chemother 58: 3354–3359.
-
27.
Kim YR, Kuh HJ, Kim MY, Kim YS, Ghung W-C, Kim S II, Kang MW, 2004. Pharmacokinetics of primaquine and carboxyprimaquine in Korean patients with vivax malaria. Arch Pharm Res 27: 576–580.
-
28.
Bhatia SC, Saraph YS, Revankar SN, Doshi KJ, Bharuca ED, Desai ED, Vaidya AB, Subrahmanyam D, Gupta KC, Satoskar RS, 1986. Pharmacokinetics of primaquine in patients with P. vivax malaria. Eur J Clin Pharmacol 31: 205–210.
-
29.
Elmes NJ, Bennett SM, Abdalla H, Carthew TL, Edstein MD, 2006. Lack of sex effect on the pharmacokinetics of primaquine. Am J Trop Med Hyg 74: 951–952.
-
30.
Cuong BT, Binh VQ, Dai B, Duy DN, Lovell CM, Rieckmann KH, Edstein MD, 2006. Does gender, food or grapefruit juice alter the pharmacokinetics of primaquine in healthy subjects? Br J Clin Pharmacol 61: 682–689.
-
31.
Singhasivanon V, Sabcharoen A, Attanath P, Chongsuphajaisiddhi T, Diquet B, Turk P, 1991. Pharmacokinetics of primaquine in healthy volunteers. Southeast Asian J Trop Med Public Health 22: 527–533.
-
32.
Binh VC, Chinh NT, Thanh NX, Cuong BT, Quang NN, Dai B, Travers T, Edstein MD, 2009. Sex affects the steady-state pharmacokinetics of primaquine but not doxycycline in healthy subjects. Am J Trop Med Hyg 81: 747–753.
-
33.
Bolchoz LJC, Budinsky RA, McMillan DC, Jollow DJ, 2001. Primaquine-induced hemolytic anemia: formation and hemotoxicity of the arylhydroxylamine metabolite 6-methoxy-8-hydroxylaminoquinoline. J Pharmacol Exp Ther 297: 509–515.
-
34.
Percario S, Moreira D, Gomes BAQ, Ferreira MED, Gonçalves ACM, Laurindo PSOC, Vilhena TC, Dolabela MF, Green MD, 2012. Oxidative stress in malaria. Int J Mol Sci 13: 16346–16372.
-
35.
World Health Organization, 2011. Methods and Techniques for Assessing Exposure to Antimalarials Drugs in Clinical Field Studies. Geneva, Switzerland: World Health Organization.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 454 | 360 | 16 |
| Full Text Views | 452 | 9 | 0 |
| PDF Downloads | 180 | 9 | 0 |
Primaquine in Plasma and Methemoglobinemia in Patients with Malaria Due to Plasmodium vivax in the Brazilian Amazon Basin
José Luiz Vieira
José Luiz Vieira
Pharmacy Faculty, Para Federal University, Belem, Brazil.
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Michelle E. S. Ferreira
Michelle E. S. Ferreira
Pharmacy Faculty, Para Federal University, Belem, Brazil.
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Michelle V. D. Ferreira
Michelle V. D. Ferreira
Pharmacy Faculty, Para Federal University, Belem, Brazil.
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Margarete M. Gomes
Margarete M. Gomes
Laboratório Central Macapa, Secretaria de Estado da Saúde do Amapá, Amapá, Brazil.
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Primaquine is the only licensed drug available for the elimination of Plasmodium vivax hypnozoites. Methemoglobinemia is currently reported in the course of treatment. There is evidence that metabolites of primaquine formed by the cytochrome pathway are responsible for methemoglobin formation; a genetic polymorphism of cytochrome isoforms; and a potential influence of gender in the activities of these enzymes requiring the establishment of dose × response curves profiles in different population groups. Concentrations of primaquine in plasma and methemoglobin levels were investigated in 54 patients with malaria due to P. vivax during the course of the standard regimen of chloroquine with primaquine (0.25 mg/kg/day for 14 days). All study subjects lived in an endemic area of the Brazilian Amazon Basin. The blood samples were collected before initiation of treatment and 3 hours (range 2–4 hours) after the administration of antimalarial drugs on days 2, 7, and 14. Plasma primaquine concentrations were similar in both genders (males: range = 164–191 ng/mL, females: range = 193–212 ng/mL). Methemoglobin levels ranged from 3.3% to 5.9% in males and from 3.1% to 6.5% in females. There were no significant correlations between the plasma primaquine concentrations or total dose and methemoglobin levels, suggesting that unidentified metabolites rather than parent drug were likely responsible for changes in methemoglobin levels. There was no significant influence of gender on primaquine concentrations in plasma or methemoglobin levels.
Author Notes
Authors' addresses: José Luiz Vieira, Michelli E. S. Ferreira, and Michelle V. D. Ferreira, Health Science Institute, Para Federal University, Belem, Brazil, E-mails: jvieira@ufpa.br and latoxufpa@gmail.com. Margarete M. Gomes, Central Laboratory of Public Health, Amapa, Brazil.
Reprint requests: José Luiz Vieira, Laboratório de Toxicologia, Faculdade de Farmácia, Universidade Federal do Pará, Campus do Guamá, Av. Augusto Corrêa 01, Belém 66075-110, Brazil, E-mail: jvieira@ufpa.br.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
World Health Organization, 2015. World Malaria Report. Geneva, Switzerland: World Health Organization.
-
2.
World Health Organization, 2010. Guidelines for the Treatment of Malaria. Geneva, Switzerland: World Health Organization.
-
3.
Hill DR, Baird JK, Parise ME, Lewis LS, Ryan ET, Magill AJ, 2006. Primaquine: report from CDC expert meeting on malaria chemoprophylaxis I. Am J Trop Med Hyg 65: 402–415.
-
4.
Vale N, Moreira R, Gomes P, 2009. Primaquine revised six decades after its discovery. Eur J Med Chem 44: 937–953.
-
5.
Baird JK, Hoffman SL, 2004. Primaquine therapy for malaria. Clin Infect Dis 39: 1336–1345.
-
6.
Robert W, Taylor J, White NJ, 2004. Antimalarials drug toxicity: a review. Drug Saf 27: 25–61.
-
7.
Hsiech HS, Jaffe ER, 1975. The metabolism of methemoglobin in human erythrocytes. Surgenor DMN, ed. The Red Blood Cell. New York, NY: Academic Press II, 799–824.
-
8.
Kiese M, 1974. Methemoglobinemia: A Comprehensive Treatise. Cleveland, OH: CRC Press.
-
9.
Carmona-Fonseca J, Álvarez G, Maestre A, 2009. Methemoglobinemia and adverse events in Plasmodium vivax malaria patients associated with high doses of primaquine treatment. Am J Trop Med Hyg 80: 188–193.
-
10.
Greaves J, Evans DAP, Fletcher KA, 1980. Urinary primaquine excretion and red cell methaemoglobin levels in man following a primaquine: chloroquine regimen. Br J Clin Pharmacol 10: 293–295.
-
11.
Cohen RJ, Sachs JR, Wicker DJ, Conrad ME, 1968. Methemoglobinemia provoked by malarial chemoprophylaxis in Vietnam. N Engl J Med 279: 1127–1131.
-
12.
Mihaly GW, Ward SA, Edwards G, Orme ML, Breckenridge AM, 1984. Pharmacokinetics of primaquine in man: identification of the carboxylic acid derivative as a major plasma metabolite. Br J Clin Pharmacol 17: 441–446.
-
13.
Ganesan S, Tekwani BL, Sahu R, Tripathi LM, Walker LA, 2009. Cytochrome P450-dependent toxic effects of primaquine on human erythrocytes. Toxicol Appl Pharmacol 241: 14–22.
-
14.
Bennett JW, Pybus BS, Yadava A, Tosh D, Sousa JC, McCarthy WF, Deye G, Melendez V, Ockenhouse CF, 2013. Primaquine failure and cytochrome P-450 2D6 in Plasmodium vivax malaria. N Engl J Med 369: 1381–1382.
-
15.
Potter BM, Xie LH, Vuong C, Zhang J, Zhang P, Duan D, Luong TL, Bandara Herath HM, Dhammika Nanayakkara NP, Tekwani BL, Walker LA, Nolan CK, Sciotti RJ, Zottig VE, Smith PL, Paris RM, Read LT, Li Q, Pybus BS, Sousa JC, Reichard GA, Marcsisin SR, 2015. Differential CYP 2D6 metabolism alters primaquine pharmacokinetics. Antimicrob Agents Chemother 59: 2380–2387.
-
16.
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, 2013. The metabolism of primaquine to its active metabolite is dependent on CYP 2D6. Malar J 12: 212–221.
-
17.
Ma MK, Woo MH, McLeod HL, 2002. Genetic basis of drug metabolism. Am J Health Syst Pharm 59: 2061–2069.
-
18.
Bertilsson L, 1995. Geographical/interracial differences in polymorphic drug oxidation. Current state of knowledge of cytochromes P450 (CYP) 2D6 and 2C19. Clin Pharmacokinet 29: 192–209.
-
19.
Meibohm B, Beierle I, Derendorf H, 2002. How important are gender differences in pharmacokinetics? Clin Pharmacokinet 41: 329–342.
-
20.
Gandhi M, Aweeka F, Greenblatt RM, Blaschke TF, 2004. Sex differences in pharmacokinetics and pharmacodynamics. Annu Rev Pharmacol Toxicol 44: 499–523.
-
21.
Oliveira-Ferreira J, Lacerda MV, Brasil P, Ladislau JL, Tauil PL, Daniel Ribeiro CT, 2010. Malaria in Brazil: an overview. Malar J 9: 115–132.
-
22.
Dua VK, Kar EK, Sarina R, Sharma VP, 1996. High-performance liquid chromatographic determination of primaquine and carboxyprimaquine concentrations in plasma and blood cells in Plasmodium vivax malaria cases following chronic dosage with primaquine. J Chromatogr B Biomed Sci Appl 657: 93–98.
-
23.
Hegesh E, Grener N, Cohen OS, Bochkousky R, Shuval HI, 1972. A sensitive micromethod for the determination of methemoglobin in blood. Clin Chim Acta 30: 679–683.
-
24.
Ward SA, Mihaly GW, Edwards G, Looareesuwan S, Phillips RE, Chanthavanich P, Warrell DA, Orme ML, Breckenridge AM, 1985. Pharmacokinetics of primaquine in man. II. Comparison of acute vs chronic dosage in Thai subjects. Br J Clin Pharmacol 19: 751–755.
-
25.
Bangchang KN, Songsaeng W, Thanavibul A, Chroenlarp P, Karbwang J, 1994. Pharmacokinetics of primaquine in G6PD deficient and G6PD normal patients with vivax malaria. Trans R Soc Trop Med Hyg 88: 220–222.
-
26.
Pukrittayakamee S, Tarning J, Jittamala P, Charunwatthana P, Lawpoolsri S, Lee SJ, Hanpithakpong W, Hanboonkunupakarn B, Day NP, Ashley EA, White NJ, 2014. Pharmacokinetic interactions between primaquine and chloroquine. Antimicrob Agents Chemother 58: 3354–3359.
-
27.
Kim YR, Kuh HJ, Kim MY, Kim YS, Ghung W-C, Kim S II, Kang MW, 2004. Pharmacokinetics of primaquine and carboxyprimaquine in Korean patients with vivax malaria. Arch Pharm Res 27: 576–580.
-
28.
Bhatia SC, Saraph YS, Revankar SN, Doshi KJ, Bharuca ED, Desai ED, Vaidya AB, Subrahmanyam D, Gupta KC, Satoskar RS, 1986. Pharmacokinetics of primaquine in patients with P. vivax malaria. Eur J Clin Pharmacol 31: 205–210.
-
29.
Elmes NJ, Bennett SM, Abdalla H, Carthew TL, Edstein MD, 2006. Lack of sex effect on the pharmacokinetics of primaquine. Am J Trop Med Hyg 74: 951–952.
-
30.
Cuong BT, Binh VQ, Dai B, Duy DN, Lovell CM, Rieckmann KH, Edstein MD, 2006. Does gender, food or grapefruit juice alter the pharmacokinetics of primaquine in healthy subjects? Br J Clin Pharmacol 61: 682–689.
-
31.
Singhasivanon V, Sabcharoen A, Attanath P, Chongsuphajaisiddhi T, Diquet B, Turk P, 1991. Pharmacokinetics of primaquine in healthy volunteers. Southeast Asian J Trop Med Public Health 22: 527–533.
-
32.
Binh VC, Chinh NT, Thanh NX, Cuong BT, Quang NN, Dai B, Travers T, Edstein MD, 2009. Sex affects the steady-state pharmacokinetics of primaquine but not doxycycline in healthy subjects. Am J Trop Med Hyg 81: 747–753.
-
33.
Bolchoz LJC, Budinsky RA, McMillan DC, Jollow DJ, 2001. Primaquine-induced hemolytic anemia: formation and hemotoxicity of the arylhydroxylamine metabolite 6-methoxy-8-hydroxylaminoquinoline. J Pharmacol Exp Ther 297: 509–515.
-
34.
Percario S, Moreira D, Gomes BAQ, Ferreira MED, Gonçalves ACM, Laurindo PSOC, Vilhena TC, Dolabela MF, Green MD, 2012. Oxidative stress in malaria. Int J Mol Sci 13: 16346–16372.
-
35.
World Health Organization, 2011. Methods and Techniques for Assessing Exposure to Antimalarials Drugs in Clinical Field Studies. Geneva, Switzerland: World Health Organization.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 454 | 360 | 16 |
| Full Text Views | 452 | 9 | 0 |
| PDF Downloads | 180 | 9 | 0 |