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効能
抗マラリア薬
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使用
Primaquine is the most effective and most toxic drug from the whole series of known
8-aminoquinolines. It is generally used for treating exoerythrocyte forms of malaria caused
by P. vivax and P. ovale. It also acts on the sexual forms of the plasmodia, which die in the
human body upon using this drug.
Primaquine is used for treating and preventing late relapses of 3- and 4-day malaria as
well as tropic malaria. Synonyms of this drug are avlon and others.
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適応症
Primaquine is the least toxic and most effective of the 8-
aminoquinoline antimalarial compounds. The mechanism
by which 8-aminoquinolines exert their antimalarial
effects is thought to be through a quinoline–quinone
metabolite that inhibits the coenzyme Q–mediated respiratory
chain of the exoerythrocytic parasite.
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定義
ChEBI: A N-substituted diamine that is pentane-1,4-diamine substituted by a 6-methoxyquinolin-8-yl group at N4 position. It is a drug used in the treatment of malaria and Pneumocystis pneumonia.
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抗菌性
Primaquine is highly active against the hepatic stages of the
malaria life cycle, including the latent hypnozoite stage of P.
vivax. It has poor activity against erythrocytic stages of malaria
parasites, other than gametocytes. The isomers have similar
antiplasmodial activity but differ in toxicity. It exhibits activity
against Pneumocystis jirovecii and, in experimental models,
against Babesia spp. and the intracellular stages of Leishmania
spp. and Trypanosoma cruzi.
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獲得抵抗性
Failure rates of up to 35% have been reported in South East Asia
in patients treated with a standard course for P. vivax infections.
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応用例（製薬）
A synthetic 8-aminoquinoline, formulated as the diphosphate
for oral administration.
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作用機序
Moving the side chain from the fourth position of the quinoline ring to the eighth position
completely changes the compound’s spectrum of activity. Unlike the 4-substituted aminoquinolines, primaquine has practically no effect on erythrocyte forms of the malaria parasite. Its activity is limited to tissue forms of the parasite in mammals and in the mosquitoes
themselves. This makes primaquine an especially valuable drug, allowing radical recovery
and simultaneous prevention, which is usually not achieved by using erythrocyte drugs.
The place of action of primaquine is the mitochondria of the malarial parasite. It seems
likely that primaquine interferes in the process of electron transfer, causing damage to
mitochondrial enzymatic systems. This is expressed in the swelling and vacuolization of
the parasite’s mitochondria. Host mitochondria are not affected.
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薬物動態学
Oral absorption: >75%
Cmax 45 mg oral: 0.2 mg/L after 2–3 h
Plasma half-life: 4–10 h
Volume of distribution: 2 L/kg
Plasma protein binding: Extensive
Bioavailability is variable after oral administration. There is
extensive tissue distribution. About 60% of the dose is metabolized
to carboxyprimaquine, which can reach levels 50 times
that of the parent drug; this metabolite has a half-life of 16 h,
a low tissue distribution and is detectable at 120 h. Methoxy
and hydroxy metabolites are also detectable. Less than 4% of
the original dose is excreted unchanged in urine.
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臨床応用
Radical cure of malaria caused by P. vivax or P. ovale
Mild or moderately severe infections with Pn. jirovecii (in combination with
clindamycin).
Because of its gametocytocidal properties, primaquine has
been used rarely in a single dose to prevent the spread of chloroquine-
resistant P. falciparum.
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副作用
At standard doses side effects are mild: abdominal cramps,
anemia, leukocytosis and methemoglobinemia. However,
primaquine
is often associated with serious adverse effects due
to the toxic metabolites 5-hydroxyprimaquine or 6-methoxy-
8-aminoquinoline which are considered to be directly responsible
for complications such as hemolytic anemia. Toxicity is
worse in people deficient of glucose-6-phosphate dehydrogenase
(G6PD) or glutathione synthetase. Adverse effects can
be further increased by the repeated administration of high
doses, due to its limited oral bioavailability.
