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. 1990;68(5):633–638.

Pharmacokinetics of mefloquine in combination with sulfadoxine-pyrimethamine and primaquine in male Thai patients with falciparum malaria.

J Karbwang 1, D J Back 1, D Bunnag 1, A M Breckenridge 1
PMCID: PMC2393179  PMID: 2289299

Abstract

The pharmacokinetics of mefloquine (M) were studied in 59 male Thai patients with falciparum malaria. Mefloquine was administered alone (750 mg orally; group 1), or with primaquine (PQ, 45 mg; group 2), or in combination with sulfadoxine (1.5 g) + pyrimethamine (75 mg) (MSP; group 3), or as MSP + PQ (group 4). All patients in groups 1, 2 and 4 initially responded to treatment, but two patients from group 1 had RI recrudescent infections. One patient in group 3 failed to respond to treatment and was considered to have RII resistance, while a further patient from this group had RI recrudescence. The pharmacokinetic parameters for group 1 and group 3 were not significantly different. Co-administration of primaquine alone had no significant effect on the pharmacokinetics of mefloquine, but there was a statistically significant decrease in the terminal elimination half-life of mefloquine for group 4 relative to that for group 3.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Back D. J., Purba H. S., Park B. K., Ward S. A., Orme M. L. Effect of chloroquine and primaquine on antipyrine metabolism. Br J Clin Pharmacol. 1983 Nov;16(5):497–502. doi: 10.1111/j.1365-2125.1983.tb02206.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Back D. J., Tjia J. F., Karbwang J., Colbert J. In vitro inhibition studies of tolbutamide hydroxylase activity of human liver microsomes by azoles, sulphonamides and quinolines. Br J Clin Pharmacol. 1988 Jul;26(1):23–29. doi: 10.1111/j.1365-2125.1988.tb03359.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Karbwang J., Back D. J., Bunnag D., Breckenridge A. M. A comparison of the pharmacokinetics of mefloquine in healthy Thai volunteers and in Thai patients with falciparum malaria. Eur J Clin Pharmacol. 1988;35(6):677–680. doi: 10.1007/BF00637607. [DOI] [PubMed] [Google Scholar]
  4. Karbwang J., Bunnag D., Breckenridge A. M., Back D. J. The pharmacokinetics of mefloquine when given alone or in combination with sulphadoxine and pyrimethamine in Thai male and female subjects. Eur J Clin Pharmacol. 1987;32(2):173–177. doi: 10.1007/BF00542191. [DOI] [PubMed] [Google Scholar]
  5. Looareesuwan S., White N. J., Warrell D. A., Forgo I., Dubach U. G., Ranalder U. B., Schwartz D. E. Studies of mefloquine bioavailability and kinetics using a stable isotope technique: a comparison of Thai patients with falciparum malaria and healthy Caucasian volunteers. Br J Clin Pharmacol. 1987 Jul;24(1):37–42. doi: 10.1111/j.1365-2125.1987.tb03133.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Mihaly G. W., Ward S. A., Nicholl D. D., Edwards G., Breckenridge A. M. The effects of primaquine stereoisomers and metabolites on drug metabolism in the isolated perfused rat liver and in vitro rat liver microsomes. Biochem Pharmacol. 1985 Feb 1;34(3):331–336. doi: 10.1016/0006-2952(85)90040-1. [DOI] [PubMed] [Google Scholar]
  7. Miller K. D., Lobel H. O., Satriale R. F., Kuritsky J. N., Stern R., Campbell C. C. Severe cutaneous reactions among American travelers using pyrimethamine-sulfadoxine (Fansidar) for malaria prophylaxis. Am J Trop Med Hyg. 1986 May;35(3):451–458. doi: 10.4269/ajtmh.1986.35.451. [DOI] [PubMed] [Google Scholar]
  8. Murray M. In vitro effects of quinoline derivatives on cytochrome P-450 and aminopyrine N-demethylase activity in rat hepatic microsomes. Biochem Pharmacol. 1984 Oct 15;33(20):3277–3281. doi: 10.1016/0006-2952(84)90090-x. [DOI] [PubMed] [Google Scholar]
  9. Peters W., Robinson B. L. The chemotherapy of rodent malaria XXXV. Further studies on the retardation of drug resistance by the use of a triple combination of mefloquine, pyrimethamine and sulfadoxine in mice infected with P. berghei and 'P. berghei NS'. Ann Trop Med Parasitol. 1984 Oct;78(5):459–466. doi: 10.1080/00034983.1984.11811850. [DOI] [PubMed] [Google Scholar]
  10. Riviere J. H., Back D. J. Effect of mefloquine on hepatic drug metabolism in the rat: comparative study with primaquine. Biochem Pharmacol. 1985 Feb 15;34(4):567–571. doi: 10.1016/0006-2952(85)90191-1. [DOI] [PubMed] [Google Scholar]
  11. Riviere J. H., Back D. J. Inhibition of ethinyloestradiol and tolbutamide metabolism by quinoline derivatives in vitro. Chem Biol Interact. 1986 Oct 1;59(3):301–308. doi: 10.1016/s0009-2797(86)80075-8. [DOI] [PubMed] [Google Scholar]
  12. Rivière J. H., Back D. J., Breckenridge A. M., Howells R. E. The pharmacokinetics of mefloquine in man: lack of effect of mefloquine on antipyrine metabolism. Br J Clin Pharmacol. 1985 Nov;20(5):469–474. doi: 10.1111/j.1365-2125.1985.tb05099.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Rozman R. S., Canfield C. J. New experimental antimalarial drugs. Adv Pharmacol Chemother. 1979;16:1–43. doi: 10.1016/s1054-3589(08)60241-0. [DOI] [PubMed] [Google Scholar]
  14. Sweeney T. R. The present status of malaria chemotherapy: mefloquine, a novel antimalarial. Med Res Rev. 1981 Fall;1(3):281–301. doi: 10.1002/med.2610010304. [DOI] [PubMed] [Google Scholar]
  15. de Souza J. M. A phase I clinical trial of mefloquine in Brazilian male subjects. Bull World Health Organ. 1983;61(5):809–814. [PMC free article] [PubMed] [Google Scholar]
  16. de Souza J. M. A phase II clinical trial of mefloquine in Brazilian male subjects. Bull World Health Organ. 1983;61(5):815–820. [PMC free article] [PubMed] [Google Scholar]

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