Archives of Pharmacal Research

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Pharmacokinetics of Primaquine and Carboxyprimaquine in Korean Patients with Vivax Malaria

  • Kim, Yang-Ree (Department of Internal Medicine, College of Medicine, The Catholic University of Korea) ;
  • Kuh, Hyo-Jeong (Research Institute of New Drug Development, The Catholic University of Kore) ;
  • Kim, Mi-Young (Department of Internal Medicine, College of Medicine, The Catholic University of Kore) ;
  • Kim, Yo-Sook (Infectious Disease Section, Catholic Research Institutes of Medical Science, The Catholic University) ;
  • Chung, Woo-Chul (Department of Internal Medicine, College of Medicine, The Catholic University of Kore) ;
  • Kim, Sang-Il (Department of Internal Medicine, College of Medicine, The Catholic University of Kore) ;
  • Kang, Moon-Won (Department of Internal Medicine, College of Medicine, The Catholic University of Korea)
  • Published : 2004.05.01
Download PDF
⟨ Previous Next ⟩

Abstract

Primaquine is used for relapses caused by vivax malaria hypnozoites. No studies on the pharmacokinetics of primaquine (PMQ) has been reported in Korean patients. In our study, thirty vivax malaria patients were given 15 mg primaquine daily for 14 days after 3 days of chloroquine treatment. Plasma samples were taken at intervals after each daily dose of PMQ for 3 days. Plasma concentrations of PMQ and carboxyprimaquine (CPMQ), the major metabolite of primaquine, were measured by HPLC. The PMQ concentrations reached a maximum of 0.28$\pm$0.18 $\mu\textrm{g}$/mL at 1.5 h after the first dose. The maximum concentration of CPMQ was 0.32$\pm$0.13 $\mu\textrm{g}$/mL at 4 h. Higher drug concentrations with repeated dosing were observed for CPMQ, but not for the parent drug, PMQ. The elimination half-life was 3.76$\pm$1.8 hand 15.7$\pm$12.2 h, for PMQ and CPMQ, respectively. Large variation in the plasma concentrations of both drugs was observed. Overall, PMQ is absorbed and metabolized rapidly after oral administration. It was noted that the mean peak plasma concentration of PMQ was significantly higher and that of CPMQ was lower in our patients compared to other studies. This suggests a potential difference of inter-ethnic groups, which warrants further investigations.

Keywords

References

  1. Anonymous., Epidemiology of malaria in Korea, 2000. CDMR., 12, 5-10(2001)
  2. Bangchang, K. N., Karbwang, J., and Back, D. J., Primaquine metabolism by human liver microsomes; effect of other antimalarial drugs. Biochem. Pharmacol., 44, 587-590 (1992) https://doi.org/10.1016/0006-2952(92)90453-P
  3. Bhatia, S. C., Saraph, Y. S., Revankar, S. N., Doshi, K. J., Bharucha, E. D., Desai, N. D., Vaidya, A. B., Subramanyam, D., Gupta, K. C., and Satoskar, R. S., Pharmacokinetics of primaquine in patients with P. vivax malaria. Eur. J. Clin. Pharm., 31, 205-210 (1986) https://doi.org/10.1007/BF00606660
  4. Bunnag, D., Karbwang, J., Thanvibul, A., Chittamas, S., Ratanapongse, Y., Chalermrut, K., Bangchang, K. N., and Harinasuta, T., High dose of primaquine in primaquine resistant vivax malaria. Trans. R. Soc. Trop. Med. Hyg., 88, 218-219 (1994) https://doi.org/10.1016/0035-9203(94)90305-0
  5. Chai, I. H., Lim, G. I., Yoon, S. N., Oh, W. I., Kim, S. J., and Chai, J. Y., Occurrence of tertian malaria in a male patient who has never been abroad. Kor. J. Parasitol., 32, 195-200 (1994) https://doi.org/10.3347/kjp.1994.32.3.195
  6. Clyde, D. F. and McCarthy, V. C., Radical cure of Chesson strain vivax malaria in man by 7, not 14, days of treatment with primaquine. Am. J. Trap. Med. Hyg., 26, 562-563 (1977)
  7. Colin, D., Primaquine. In Colin., D., Boobis, A. R., Burley. D., Davies, D. M., Davies., D. S., Harrison. P. I., Orme. M. L., Park. B. K., and Goldberg. L. I. (Eds.). Therapeutic Drug. Edinbergh:Churchill Livingston, New York, pp.209-212, (1991)
  8. Constantino, L., Paixao, P., Moreira, R., Portela, M. J., Do Rosario, V. E., and lley, J., Metabolism of primaquine by liver homogenate fractions. Evidence for monoamine oxidase and cytochrome P450 involvement in the oxidative deamination of primaquine to carboxyprimaquine. Exp. Toxicol. Pathol,. 51, 299-303 (1999) https://doi.org/10.1016/S0940-2993(99)80010-4
  9. Dua, V. K., Kar, P. K., Sarin. R., and Sharma, V. P., 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., 675, 93-98 (1996) https://doi.org/10.1016/0378-4347(95)00357-6
  10. Endoh, Y. S., Yoshimura, H., Sasaki, N., Ishihara, Y., Sasaki, H., Nakamura, S., Inoue, Y., and Nishikawa, M., High-performance liquid chromatographic determination of pamaquine, primaquine and carboxyprimaquine in calf plasma using electrochemical detection. J. Chromatogr., 592, 123-129 (1992)
  11. Fletcher, K. A., Evans, D. A., Gilles, H. M., Greaves, J., Bunnag, D., and Harinasuta, T., Studies on the pharmacokinetics of primaquine. Bull. World Health Organ., 59, 407-412 (1981)
  12. Gashaw, I., Kirchheiner, J., Goldammer, M., Bauer, S., Seidemann, J., Zoller, K., Mrozikiewicz, P. M., Roots, I., and Brockmoller, J., Cytochrome P450 3A4 messenger ribonucleic acid induction by rifampin in human peripheral blood mononuclear cells: correlation with alprazolam pharmacokinetics. Clin. Pharmacol. Ther., 774, 448-457 (2003)
  13. Greaves, J., Evans, D. A., Gilles, H. M., Fletcher, K. A., Bunnag, D., and Harinasuta, T., Plasma kinetics and urinary excretion of primaquine in man. Brit. J. Clin. Pharmacol., 10, 399-405 (1980)
  14. Kennedy, E. and Frischer, H., Distribution of primaquine in human blood: drug-binding to ${\alpha}_{1}$-glycoprotein. J. Lab. Clin. Med., 116, 871-878 (1990)
  15. Kim, J. H., Park, K. S., Lee, J. M., Choi, J. H., Lee, I. S., Kim, M. Y., Kim, Y. R., and Kang, M. W., A case of primaquine-resistant tertian malaria. Kor. J. Infect. Dis., 29, 503-507 (1997) https://doi.org/10.3109/00365549709011863
  16. Kimura, M., Tomizawa, I., Takizwa, Y., and Ohtomo, H., A study of relapsed cases of vivax malaria after the standard primaquine therapy. Kansenshogaku Zasshi., 70, 1086-1091 (1996)
  17. Law, M. Y., Slawson, M. H., and Moody, D. E., Selective involvemnet of cytochrome P450 2D subfamily in in vivo 4-hydroxylation of amphetamine in rat. Drug Metab. Dispos., 28, 348-353 (2000)
  18. McEvoy. G. K., Primaquine phosphate. In McEvoy, G. K., Miller. J. L., Snow. E. K., and Welsh. O. H. (Eds.). AHFS Drug information. ASHP Inc., Bethesda, pp.754-756, (2002)
  19. Mihaly, G. W., Nicholl, D. D., Ward, S. A., Edwards, G., Orme, M. L., and Breckenridge, A. M., Pharmacokinetics of prmaquine in man: Identification of the carboxylic acid derivative as a major plasma metabolite. Brit. J. Clin. Pharmacol., 17, 441-446 (1984) https://doi.org/10.1111/j.1365-2125.1984.tb02369.x
  20. Mihaly, G. W., Ward, S. A., Edwards, G., Nicholl, D. D., Orme, M. L., and Breckenridge, A. M., Pharmacokinetics of primaquine in man. I. Studies of the absolute bioavailability and effects of dose size. Brit. J. Clin. Pharmacol., 19, 745-750 (1985) https://doi.org/10.1111/j.1365-2125.1985.tb02709.x
  21. Pukrittayakamee, S., Vanijanonta, S., Chantra, A., Clemens, R., and White, N. J., Blood stage antimalarial efficacy of primaquine in Plasmodium vivax malaria. J. Infect. Dis., 169, 932-935 (1994) https://doi.org/10.1093/infdis/169.4.932
  22. Rieckmann, K. H., Yeo, A. E., Davis, D. R., Hutton, D. C., Wheatley, P. F., and Simpson, R., Recent military experience with malaria chemoprophylaxis. Med. J. Aust., 158, 446-449 (1993)
  23. Ward, S. A., Mihaly, G. W., Edwards, G., Looareesuwin, S., Phillips, R. E., Chanthavanich, P., Warrell, D. A., Orme, M. L., and Breckenridge, A. M., Pharmacokinetics of primaquine in Man. II. Comparison of acute vs chronic dosage in Thai subjects. Br. J. Clin. Pharmacol., 19, 751-755 (1985) https://doi.org/10.1111/j.1365-2125.1985.tb02710.x
  24. Zhao, X. J. and Ishizaki, T., A further interaction study of quinine with clinically important drugs by human liver microsomes: determinations of inhibition constant (Ki) and type of inhibition. Eur. J. Drug Metab. Pharmacokinet., 24, 272-278 (1999). https://doi.org/10.1007/BF03190031