1921
Volume 68, Issue 1
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Published pharmacokinetic data indicate that after treatment of patients with therapeutic doses of atovaquone/proguanil hydrochloride (Malarone™, GlaxoSmithKline Research Triangle Park, NC), the plasma half-lives of these drugs are 70h and 15h, respectively. However, using two biologic assays (mosquito transmission and asexual stage development), we demonstrate here that sera from volunteers treated with atovaquone/proguanil retained activity against up to 6 weeks after such treatment. This activity was due to atovaquone, as administration of this drug alone replicated the data obtained with the combination. Most notably, asexual stage development of an atovaquone-resistant strain (NGATV01) of was not inhibited by sera taken after atovaquone treatment. These data indicate that for atovaquone, biologic assays, though not quantitative, are more sensitive than the usual physicochemical assays. Also, persistence of atovaquone in plasma at low concentrations for long periods may increase the risk of resistant parasites arising.

Loading

Article metrics loading...

/content/journals/10.4269/ajtmh.2003.68.111
2003-01-01
2017-09-26
Loading full text...

Full text loading...

/deliver/fulltext/14761645/68/1/0680111.html?itemId=/content/journals/10.4269/ajtmh.2003.68.111&mimeType=html&fmt=ahah

References

  1. Peters W, 1984. Use of drug combinations. Peters W, Richards WHG, eds. Antimalarial Drugs, vol 2. London: Springer-Verlag, 499–509.
  2. Butcher G, 1997. Antimalarial drugs and the mosquito transmission of Plasmodium. Int J Parasitol 27 : 975–987.
  3. Sabchereon A, Attanath P, Phanuasksook P, Chanthavanich P, Poonpanich T, Mookmanee D, Chongsuphajaisiddhi T, Sadler BM, Hussein Z, Canfield CJ, Hutchinson DBA, 1998. Efficacy and pharmacokinetics of atovaquone and proguanil in children with multi-drug resistant Plasmodium falciparum malaria. Trans R Soc Trop Med Hyg 92: 201–206.
  4. Shanks GD, Kremsner PG, Such TY, van der Berg J, Shapiro TA, Scott TR, Chulay JD, 1999. Atovaquone and proguanil hydrochloride (MALARONE™) for prophylaxis of malaria. J Travel Med 6 (Suppl 1) : S21–S27.
  5. Beerahee M, 1999. Clinical pharmacology of atovaquone and proguanil hydrochloride. J Travel Med 6 (Suppl 1) : S13–S17.
  6. Hudson AT, 1993. Atovaquone—a novel broad-spectrum anti-infective drug. Parasitol Today 9 : 66–68.
  7. Butcher GA, Mendoza J, Sinden RE, 2000. Inhibition of the mosquito transmission of Plasmodium berghei by Malarone™ (atovaquone/proguanil). Ann Trop Med Parasitol 94: 429–436
  8. Ponnudurai TV, Lensen AHW, Leeuwenberg ADEM, Meuwissen JHET, 1982. Cultivation of fertile Plasmodium falciparum gametocytes in semi-automated systems. Trans R Soc Trop Med Hyg 76 : 242–250.
  9. Butcher GA, Sinden RE, Billker O, 1996. Plasmodium berghei: infectivity of mice to Anopheles stephensi mosquitoes. Exp Parasitol 84 : 371–379.
  10. Høgh B, Gamage-Mendis A, Butcher GA, Thompson R, Begtrup K, Mendis C, Enosse SM, Dgedge M, Barreto J, Eling W, Sinden RE, 1998. The differing impact of chloroquine and pyrimethamine/sulfadoxine upon the infectivity of malaria spp. to the mosquito vector. Am J Trop Med Hyg 58 : 176–182.
  11. Fivelman QL, Butcher GA, Adagu IS, Warhurst DC, Pasvol G, 2002. Malarone treatment failure and in vitro confirmation of resistance of Plasmodium falciparum isolate from Lagos, Nigeria. Malaria J 1 : 1–4.
  12. Butcher GA, Clark IA, Crane G, 1987. Inhibition of intraerythrocytic growth of P. falciparum by human sera from Papua New Guinea. Trans R Soc Trop Med Hyg 81 : 568–572.
  13. Lindegardh N, Fundling L, Bergvist Y, 2001. Automated solid-phase extraction method for the determination of atovaquone in capillary blood applied onto sampling paper by rapid high-performance liquid chromatography. J Chromatog B: Biomed Sci Appl 758 : 137–144.
  14. Huang W, Foster JA, Rogchefsky AS, 2000. Pharmacology of botulinum toxin. J Am Acad Dermatol 43 : 249–259.
  15. Looareesuwan S, Viravin C, Webster HK, Kyle DE, Hutchinson DB Canfield CJ. 1996. Clinical studies of atovaquone, alone or in combination with other antimalarial drugs, for the treatment of acute uncomplicated malaria in Thailand. Am J Trop Med Hyg 54: 52–56.
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.2003.68.111
Loading
/content/journals/10.4269/ajtmh.2003.68.111
Loading

Data & Media loading...

  • Received : 17 Apr 2002
  • Accepted : 22 Aug 2002

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error