The pharmacokinetic properties of intramuscular artesunate and rectal dihydroartemisinin in uncomplicated falciparum malaria

Aims  To obtain pharmacokinetic data for artesunate (ARTS) and its active metabolite dihydroartemisinin (DHA) following i.m. ARTS and rectal DHA administration. Methods  Twelve Vietnamese patients with uncomplicated falciparum malaria were randomized to receive either i.v. or i.m. ARTS (120 mg), wit...

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Bibliographic Details
Published in:British journal of clinical pharmacology 2002-01, Vol.53 (1), p.23-30
Main Authors: Ilett, Kenneth F., Batty, Kevin T., Powell, Shane M., Binh, Tran Quang, Thu, Le Thi Anh, Phuong, Hoang Lan, Hung, Nguyen Canh, Davis, Timothy M. E.
Format: Article
Language:English
Subjects:
Administration, Rectal
Adult
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antimalarials - administration & dosage
Antimalarials - pharmacokinetics
Antiparasitic agents
Area Under Curve
Artemisinins
Artesunate
Biological and medical sciences
Confidence Intervals
Cross-Over Studies
dihydroartemisinin
falciparum malaria
Female
Humans
Injections, Intramuscular
Injections, Intravenous
intramuscular injection
Malaria, Falciparum - drug therapy
Malaria, Falciparum - metabolism
Male
Medical sciences
Pharmacokinetics
Pharmacology. Drug treatments
rectal administration
Sesquiterpenes - administration & dosage
Sesquiterpenes - pharmacokinetics
Statistics, Nonparametric
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Summary:Aims  To obtain pharmacokinetic data for artesunate (ARTS) and its active metabolite dihydroartemisinin (DHA) following i.m. ARTS and rectal DHA administration. Methods  Twelve Vietnamese patients with uncomplicated falciparum malaria were randomized to receive either i.v. or i.m. ARTS (120 mg), with the alternative preparation given 8 h later in an open crossover design. A further 12 patients were given i.v. ARTS (120 mg) at 0 h and rectal DHA (160 mg) 8 h later. Results  Following i.v. bolus, ARTS had a peak concentration of 42 µm (16 mg l−1), elimination t1/2 = 3.2 min, CL = 2.8 l h−1 kg−1 and V = 0.22 l kg−1. The Cmax for DHA was 9.7 µm (2.7 mg l−1), t1/2 = 59 min, CL = 0.64 l h−1 kg−1 and V =  0.8 l kg−1. Following i.m. ARTS, Cmax was 2.3 µm (3.7 mg l−1), the apparent t1/2 = 41 min, CL = 2.9 l h−1 kg−1 and V = 2.6 l kg−1. The relative bioavailability of DHA was 88%, Cmax was 4.1 µm (1.16 mg l−1) and t1/2 = 64 min. In the rectal DHA study, relative bioavailability of DHA was 16%. Conclusions  For patients with uncomplicated falciparum malaria i.m. ARTS is a suitable alternative to i.v. ARTS, at equal doses. To achieve plasma DHA concentrations equivalent to parenteral administration of ARTS, rectal DHA should be given at approximately four‐fold higher milligram doses. Further studies are needed to determine whether these recommendations can be applied to patients with severe malaria.
ISSN:0306-5251
1365-2125
DOI:10.1046/j.0306-5251.2001.01519.x