Pharmacokinetic and pharmacodynamic evaluation of intramuscular artesunate in healthy beagle dogs.
Am J Trop Med Hyg
; 79(1): 36-41, 2008 Jul.
Article
en En
| MEDLINE
| ID: mdl-18606761
ABSTRACT
Pharmacokinetic and pharmacodynamic responses were evaluated after intramuscular (i.m.) injection of artesunate (AS). Twelve dogs were injected with i.m. 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, i.m. AS resulted in a prolonged half-life for both AS and DHA. Intramuscular AS also had a lower mean dose-adjusted C(max) and a higher mean dose-adjusted area under the curve; but produced similar concentrations of dihydroartemisinin. These findings suggest that adverse reactions to i.m. artesunate are minor and temporary which justify further study of this route in treating severe malaria.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Músculo Esquelético
/
Creatina Quinasa
/
Artemisininas
/
Malaria
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Am J Trop Med Hyg
Año:
2008
Tipo del documento:
Article
País de afiliación:
Estados Unidos