1921
Volume 79, Issue 1
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Pharmacokinetic and pharmacodynamic responses were evaluated after intramuscular (IM) injection of artesunate (AS). Twelve dogs were injected with IM AS at 2.5, 5, or 10 mg/kg into the left gluteal muscle. A second injection of only diluent was given in the right gluteal muscle. At 24 hours post-injection, plasma creatine kinase (CK) concentrations were elevated above normal. Muscle biopsies showed myocyte necrosis and acute inflammation, which was worse on the treated side. At 7 days after injection, CK concentrations were normal. Muscle biopsies showed mineralization, fibrosis, and chronic inflammation with less difference between sides. Compared with intravenous administration, IM AS resulted in a prolonged half-life for both AS and DHA. Intramuscular AS also had a lower mean dose-adjusted and a higher mean dose-adjusted area under the curve; but produced similar concentrations of dihydroartemisinin. These findings suggest that adverse reactions to IM artesunate are minor and temporary which justify further study of this route in treating severe malaria.

Loading

Article metrics loading...

/content/journals/10.4269/ajtmh.2008.79.36
2008-07-01
2017-11-25
Loading full text...

Full text loading...

/deliver/fulltext/14761645/79/1/0790036.html?itemId=/content/journals/10.4269/ajtmh.2008.79.36&mimeType=html&fmt=ahah

References

  1. Nealon C, Dzeing A, Muller-Romer U, Planche T, Sinou V, Kombila M, Kremsner P, Parzy D, Krishna S, 2002. Intramuscular bioavailability and clinical efficacy of artesunate in Gabonese children with severe malaria. Antimicrob Agents Chemother 46 : 3933–3939.
  2. Hien TT, Davis TM, Chuong LV, Ilett KF, Sinh DXT, Phu NH, Agus C, Chiswell GM, White NJ, Farrar J, 2004. Comparative pharmacokinetics of intramuscular artesunate and artemether in patients with severe falciparum malaria. Antimicrob Agents Chemother 48 : 4234–4239.
  3. Hien TT, Day NP, Phu NH, Mai NTH, Chau TTH, Loc PP, Sinh DX, Chuong LV, Vinh H, Waller D, Peto TE, White NJ, 1996. A controlled trial of artemether or quinine in Vietnamese adults with severe falciparum malaria. N Engl J Med 335 : 76–83.
  4. Dondorp A, Nosten F, Stepniewska K, Day N, White N, 2005. Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial. Lancet 366 : 717–725.
  5. Batty KT, Thu LTA, Ilett KF, Tien NP, Powell SM, Hung NC, Mai TX, Chon VV, Thien HV, Binh TQ, Kim NV, Davis TM, 1998. A pharmacokinetic and pharmacodynamic study of arte-sunate for vivax malaria. Am J Trop Med Hyg 59 : 823–827.
  6. Griffith KS, Lewis LS, Mali S, Parise ME, 2007. Treatment of malaria in the United States: a systemic review. JAMA 297 : 2264–2277.
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.2008.79.36
Loading
/content/journals/10.4269/ajtmh.2008.79.36
Loading

Data & Media loading...

  • Received : 29 Apr 2007
  • Accepted : 20 Apr 2008

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