Page 97 - 80 guidelines for the treatment of malaria_opt

ANNEX 3. Pharmacology of antimalarial medicines

are given orally, or with similar doses of water-soluble drugs such as artesunate. Clinical,
neurophysiological and pathological studies in humans have not shown similar findings
with therapeutic use of these compounds (40). Toxicity is otherwise similar to that of
CI N CI N
artemisinin.
N
H N
N N Drug interactions
2
O O CH 3
HN CH 3 HN S CH 3 None known.
N
N CH 3 N O
H
O NH 2
OH CH 3 H N CH 3 CI
A3
2
N CH 3
H 3 C A3.6.3 Artesunate
Molecular weight: 384.4

F Artesunate is the sodium salt of the
H 3 C H 3 C H 3 C
F F hemisuccinate ester of artemisinin.
F
F It is soluble in water but has poor
N O O O
O C O C O C stability in aqueous solutions at
F O O O neutral or acid pH. In the injectable
ÿ O CH 3 O CH 3 O O CH 3 form, artesunic acid is drawn up in
H H H H 3 C H H HO H H
HO O O O sodium bicarbonate to form sodium
H H H artesunate immediately before
HN CH 3 CH 3 O CH 3
injection.
Artesunate can be given orally, rectally or by the intramuscular or intravenous routes.

H 3 C H 3 C CI Formulations
• Tablets containing 50 mg or 200 mg of sodium artesunate.
CH 3
O O C O O C HN NH 2
O O • Ampoules for intramuscular or intravenous injection containing 60 mg of anhydrous
N
CH 3 CH 3 CI CI artesunaic acid with a separate ampoule of 5% sodium bicarbonate solution.
O O
H H H H • Rectal capsules containing 100 mg or 400 mg of sodium artesunate.
H 3 C H 3 C
HO H 3 C O O
H H Pharmacokinetics
CH 3 CH 3 H 3 C N
OH
Artesunate is rapidly absorbed, with peak plasma levels occurring 1.5 h, 2 h and 0.5 h after
oral, rectal and intramuscular administration, respectively (43–47). It is almost entirely
converted to dihydroartemisinin, the active metabolite (30). Elimination of artesunate is
very rapid, and antimalarial activity is determined by dihydroartemisinin elimination
CI CI
H H H (half-life approximately 45 min) (40). The extent of protein binding is unknown. No dose
N N N CH 3 CI O
H NH NH CH 3 modifications are necessary in renal or hepatic impairment.
H N S NH 2
2
NH NH CH 3
CI H H H O
O N N N CH 3 83
H
OH
O

H 2 C H H 3 C CH 3 OH CI
HO CH 3 H N OH O O O CH 3 O CH 3
OH OH N
NH N
N 2 H H
H 3 C O
HO H NH 2 CH 3
OH H HO S
OH H H
O OH O OH O O
H 3 C H 3 C OH N HO OH
H 3 C CH 3
N