The pharmacokinetic properties of intramuscular artesunate and rectal dihydroartemisinin in uncomplicated falciparum malaria.
OBJECTIVE
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 microm (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 microm (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 microm (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 microm (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.
Ilett
Kenneth F
KF
Department of Pharmacology, University of Western Australia, Nedlands 6009 Western Australia. kilett@receptor.pharm.uwa.edu.au
Batty
Kevin T
KT
Powell
Shane M
SM
Binh
Tran Quang
TQ
Thu
Le Thi Anh
le TA
Phuong
Hoang Lan
HL
Hung
Nguyen Canh
NC
Davis
Timothy M E
TM
D000285:Administration, Rectal; D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D037621:Artemisinins; D000077332:Artesunate; D016001:Confidence Intervals; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018709:Statistics, Nonparametric
D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; D000077332:Artesunate; C039060:artenimol