The disposition of intramuscular artemether in children with cerebral malaria; a preliminary study

The disposition of intramuscular artemether (AM) was studied in 26 Kenyan children with cerebral malaria. Antimalarial activity determined by bioassay was compared with total plasma AM plus dihydroartemisinin (DHA) determined by high power liquid chromatography (HPLC). Therapeutic levels were achiev...

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Bibliographic Details
Published in:Transactions of the Royal Society of Tropical Medicine and Hygiene Vol. 91; no. 3; p. 331
Main Authors: Murphy, S A, Mberu, E, Muhia, D, English, M, Crawley, J, Waruiru, C, Lowe, B, Newton, C R, Winstanley, P, Marsh, K, Watkins, W M
Format: Journal Article
Language:English
Published: England 01.05.1997
Subjects:
Antimalarials - administration & dosage
Antimalarials - blood
Antimalarials - pharmacokinetics
Artemether
Artemisinins
Biological Availability
Child
Child, Preschool
Chromatography, High Pressure Liquid
Female
Humans
Infant
Injections, Intramuscular
Kenya
Malaria, Cerebral - blood
Malaria, Cerebral - drug therapy
Male
Respiratory Insufficiency - complications
Sesquiterpenes - administration & dosage
Sesquiterpenes - blood
Sesquiterpenes - pharmacokinetics
Time Factors
Treatment Outcome
ISSN:0035-9203
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Summary:The disposition of intramuscular artemether (AM) was studied in 26 Kenyan children with cerebral malaria. Antimalarial activity determined by bioassay was compared with total plasma AM plus dihydroartemisinin (DHA) determined by high power liquid chromatography (HPLC). Therapeutic levels were achieved in most subjects (21/26) within 1 h of receiving intramuscular AM (3.2 mg/kg), with close correlation between bioassay and HPLC measurements (r = 0.706). However, there was marked inter-individual variation, antimalarial activity was undetectable in 5 subjects ('non-absorbers'), and plasma concentrations were lower in subject with respiratory distress. The 50% parasite clearance time was significantly longer in non-absorbers (mean = 13.1 h, SD = 10.8 vs. mean = 7.8 h, SD = 5.5; P = 0.013). We conclude that the bioavailability of intramuscular AM in children with severe malaria may be highly variable, particularly in the presence of respiratory distress, and may be associated with an inadequate therapeutic response.
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ISSN:0035-9203
DOI:10.1016/S0035-9203(97)90097-3