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N
CI
N
CI
2
HN
HN
CH 3
N CH 3 O S O N N N O CH 3 H N N N CH 3
H
O NH 2
OH CH 3 H N CH 3 CI
2
nd
Guidelines for the treatment of malaria – 2 edition
N CH 3
H 3 C
Toxicity
As for artemisinin.
F
Drug interactions H 3 C H 3 C H 3 C
F F
F
None known. F
N
O O C O O C O O C
F O O O
ÿ O CH 3 O CH 3 O O CH 3
H H H H 3 C H H HO H H
HO O O O
H H H
A3.6.4 Dihydroartemisinin CH 3 CH 3 O CH 3
HN
Molecular weight: 284.4
Dihydroartemisinin is the main active metabolite
H 3 C H 3 C CI
of the artemisinin derivatives, but can also be
CH 3
given orally and rectally as a drug in its own right.
O
O
O C O C HN NH 2
O, and requires
O It is relatively insoluble in water
CH 3
CH 3 formulation with suitable excipients to ensure CI CI N
O O
H
H
H H adequate absorption. It achieves cure rates similar
H 3 C artesunate. A fixed dose formulation
HO to those of oral O H 3 C H 3 C O
H
H with piperaquine is currently undergoing evaluation
CH 3 CH 3 H 3 C N
as a promising new artemisinin-based combination OH
treatment (ACT).
Formulations
• Tablets containing 20 mg, 60 mg or 80 mg of dihydroartemisinin. CI
CI
• Suppositories containing 80 mg of dihydroartemisinin. H H H CH 3 CI O
N
N
N
H NH NH CH 3
Pharmacokinetics NH NH CH 3 H N S NH 2
2
CI H H H CH 3 O
Dihydroartemisinin is rapidly absorbed following oral administration, reaching peak N N N
O
levels after around 2.5 h. Absorption via the rectal route is somewhat slower, with
H
peak levels occurring around 4 h after administration. Plasma protein binding is
around 55%. Elimination half-life is approximately 45 minutes via intestinal and hepatic
OH
O
glucuronidation (48).
Toxicity
As for artemisinin.
H 2 C H H 3 C CH 3 OH CI
Drug interactions HO CH 3 H N OH O O O CH 3 O CH 3
OH OH N
None known. NH N
N 2 H H
H 3 C O CH 3
84 HO H NH 2 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