The exact mechanism of action of Primaquine is not well understood. It may act by generating reactive oxygen species or by interfering with electron transport in the parasite. It binds to and alters the properties of protozoal DNA. Primaquine's major metabolite is carboxyprimaquine. Its unique action on latent liver stages and gametocytes makes it essential in malaria eradication efforts.

In vitro, Primaquine has antimalarial activity against various stages of the Plasmodium parasite. It has also been shown to inhibit the endosomal trafficking and nuclear localization of EGFR and induce apoptosis of breast cancer cells by nuclear EGFR/Stat3-mediated c-Myc downregulation. Specific IC₅₀ values for its antimalarial activity are not provided in the available sources.

In vivo, Primaquine is used clinically as an antimalarial drug. It is indicated to prevent relapse of vivax malaria and is used in combination with other antimalarials for the treatment of Plasmodium vivax and ovale infections. It is also used to treat Pneumocystis carinii pneumonia. Its efficacy in eliminating liver stages and gametocytes has been established in clinical use.

A cell-free assay for Primaquine is not applicable as it is not an enzyme inhibitor with a well-defined target. Its antimalarial activity is assessed in parasite cultures. Its ability to generate reactive oxygen species can be measured in cell-free systems. Its binding to DNA could be assessed using spectroscopic methods.

Cellular assays for Primaquine typically involve assessing its antimalarial activity against Plasmodium parasites in culture. Parasite growth inhibition is measured after treatment with varying concentrations of the compound. Primaquine has also been studied in cancer cell lines for its effects on EGFR signaling and apoptosis. Specific protocols are not detailed in the available sources.

In vivo animal experiments for Primaquine are not described in the available sources. As a clinically used drug, its efficacy and safety have been established in human studies. Preclinical studies in animal models of malaria likely contributed to its development, but specific protocols and data are not provided.

Absorption, Distribution and Excretion
Absorption is rapid; bioavailability is approximately 96%. Primaquine is well absorbed from the gastrointestinal tract. Peak plasma concentrations are typically reached within 6 hours after oral administration; plasma concentrations are usually negligible after 24 hours. Significant individual variability in peak plasma concentrations has been reported even when administering the same dose of primaquine. While specific information regarding the distribution of primaquine in tissues and fluids is lacking, the drug appears to be widely distributed in the body after oral administration. The apparent volume of distribution of primaquine in healthy adults is approximately 150 to 250 liters. It is widely distributed; in one study, the whole blood to plasma distribution ratio was 0.93 in patients treated with 15 mg (bases) daily for 14 days. For more complete data on the absorption, distribution, and excretion of primaquine (7 metabolites), please visit the HSDB records page.

---

Metabolism/Metabolites
Primaquine's major metabolite is carboxyprimaquine, which has a much higher plasma concentration than unmetabolized primaquine.
It is currently unclear whether carboxyprimaquine possesses antimalarial activity.
Primaquine is rapidly metabolized…The three identified oxidative metabolites are 8-(3-carboxy-1-methylpropylamino)-6-methoxyquinoline, 5-hydroxyprimaquine, and 5-hydroxy-6-demethylprimaquine. The carboxyl derivative is the major metabolite in human plasma. After a single dose, its plasma concentration can be more than 10 times that of primaquine; this non-toxic metabolite is slowly cleared and accumulates after multiple doses…The antimalarial activity of these three metabolites…appears to be significantly lower than that of primaquine. However, except for the carboxyl derivative, their hemolytic activity (assessed by in vitro methemoglobin formation) is higher than that of the parent compound.

---

Biological Half-Life
3.7-7.4 hours
Primaquine has a plasma half-life of 3.7-9.6 hours in healthy adults.
Carboxyprimaquine has a half-life of 22-30 hours.

Primaquine has a half-life of about 6 hours, and its major metabolite, carboxyprimaquine, has a half-life of 22 to 30 hours. The compound is administered orally. Its pharmacokinetic properties are consistent with those of other 8-aminoquinolines. Specific PK parameters, such as clearance and volume of distribution, are not provided in the available sources.

Hepatotoxicity
Although primaquine has been used for over 50 years, it has not been found to be associated with significant elevations in serum transaminases or clinically significant acute liver injury. Primaquine can cause hemolysis in patients with G6PD deficiency, leading to mild jaundice.
Probability score: E (unlikely a cause of clinically significant liver injury).

---

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation Primaquine and its metabolites are rarely excreted into the breast milk of lactating mothers and are undetectable in the serum of breastfed infants. No signs of hemolysis have been observed in breastfed infants after the neonatal period. Studies have not been conducted on newborns and infants with glucose-6-phosphate dehydrogenase (G6PD) deficiency, but the risk of hemolysis through breast milk exposure in G6PD-deficient infants older than 28 days appears to be low. If primaquine is required, it is recommended that both the mother and infant be tested for G6PD deficiency before administration to a breastfeeding mother. The UK malaria treatment guidelines recommend that breastfeeding mothers with malaria avoid primaquine and suggest taking 500 mg of chloroquine weekly until breastfeeding is discontinued. However, these guidelines were developed before information on primaquine excretion in breast milk and its safety for breastfed infants was published. Updated information indicates that all mothers breastfeeding infants older than 28 days can safely take primaquine. The US Centers for Disease Control and Prevention (CDC) guidelines state that primaquine can be used by breastfeeding mothers and infants with normal G6PD levels. Because the amount of primaquine in breast milk is extremely low and insufficient to provide adequate protection or treatment against malaria, infants requiring chemoprevention or treatment must receive the recommended dose of primaquine.
◉ Effects on breastfed infants
21 mothers with vivax malaria took 0.5 mg/kg of primaquine daily for 14 days while breastfeeding infants at least 28 days old. No abnormalities were observed in hematocrit, Heinz body count, serum bilirubin, oxygen saturation, or methemoglobinemia in any of the infants.
A woman with vivax malaria, 5 months postpartum, was given 0.52 mg/kg primaquine daily for 7 days after a follow-up weight check, followed by 0.46 mg/kg daily for 7 days. Sh was diagnosed as a heterozygote for glucose-6-phosphate dehydrogenase (G6PD) deficiency and presented with hemolysis and anemia. Her daughter, who was breastfed during treatment (feeding extent not specified), was diagnosed as a heterozygote for the G6PD Mahidol variant but did not present with significant hemolysis. The infant has completed vaccinations and showed normal motor development milestones at 6 months of age.
◉ Effects on lactation and breast milk
As of the revision date, no relevant published information was found.
Toxicity data for Primaquine are not detailed in the available sources. As a clinically used drug, its safety profile is known. Common adverse effects include gastrointestinal upset and hemolytic anemia, particularly in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Specific toxicological information is not provided in the references cited.

Primaquine is an N-substituted diamine with the structure pentane-1,4-diamine, substituted at the N(4) position with a 6-methoxyquinoline-8-yl group. It is a drug used to treat malaria and Pneumocystis carinii pneumonia, possessing antimalarial activity. It is an aminoquinoline compound, belonging to the N-substituted diamine class, and is also an aromatic ether compound.
Primaquine phosphate is a prescription antimalarial drug approved by the U.S. Food and Drug Administration (FDA) for the prevention of relapse of malaria caused by Plasmodium vivax.
Malaria can be an opportunistic infection of HIV infection. Opportunistic infections are those that are more common or more severe in people with weakened immune systems (such as those infected with HIV) than in people with healthy immune systems.
Primaquine is an oral aminoquinoline drug used to eradicate vivax and ovale malaria and to prevent relapse after treatment with blood schizonticides. It has also been used to prevent the spread of falciparum malaria from returning populations to areas where malaria may re-enter. Adverse reactions include anemia and gastrointestinal disturbances. (Excerpt from Martindale Pharmacopoeia, 30th Edition, page 404)
Primaquine is an antimalarial drug.
Primaquine is an aminoquinoline drug that has been used for the prevention and treatment of malaria for over 50 years. Primaquine does not cause elevated serum enzymes during treatment and has not been found to be associated with clinically significant cases of acute liver injury.
Primaquine has been reported to cause infection with Streptomyces rimosus, and relevant data exist.
Primaquine is a synthetic 8-aminoquinoline derivative with antimalarial properties. Although its mechanism of action is not fully understood, primaquine binds to protozoan DNA and alters its properties. This drug clears tissue (extraerythrocytic stage) Plasmodium infection, thereby preventing the development of erythrocytic parasites that lead to relapses of Plasmodium vivax and Plasmodium ovale. Primaquine is also effective against late hepatic stages (dormant zoan, schizont). (NCI04)
Oral aminoquinoline drugs are used to eradicate infection with Plasmodium vivax and Plasmodium ovale and to prevent relapse after treatment with blood schizonticides. It has also been used to prevent the transmission of Plasmodium falciparum malaria by individuals returning to areas where malaria may re-enter. Adverse reactions include anemia and gastrointestinal disturbances. (From Martindale Pharmacopoeia, 30th edition, p. 404)
See also: Primaquine phosphate (in saline form).
Drug Indications

For the treatment of malaria.
FDA Label

Mechanism of Action

The mechanism of action of primaquine is not fully understood. It may act by generating reactive oxygen species or interfering with electron transport in the parasite. Furthermore, although its mechanism of action is not fully understood, primaquine may bind to protozoan DNA and alter its properties.
The exact mechanism of action has not been determined, but it is likely based on primaquine's ability to bind to DNA and alter its properties. Primaquine is highly active against the extraerythrocytic stages of Plasmodium vivax and Plasmodium ovale, as well as the primary extraerythrocytic stage of Plasmodium falciparum. It is also highly active against the sexual reproductive stage (gametophyte) of Plasmodium, especially Plasmodium falciparum, and can block disease transmission by eliminating mosquito-borne sources of infection. Primaquine can damage the mitochondria of the parasite, thereby interfering with energy-requiring metabolic processes. …Primaquine is a class of aromatic amine-containing exogenous substances that can induce oxidative damage in erythrocytes. These substances appear to enhance normal redox reactions and overcome normal protective mechanisms. The interaction of these exogenous substances with hemoglobin leads to the formation of free radicals, resulting in the denaturation of key proteins, including hemoglobin, thiol-dependent enzymes, and erythrocyte membrane components…Oxidative denaturation of globin chains reduces their affinity for heme groups, which may dissociate from the globin chains during oxidative damage…The generation of free radicals may also lead to membrane lipid peroxidation. This may affect the deformability of erythrocytes and the permeability of the cell membrane to potassium ions. Alterations in the Na⁺/K⁺ gradient can pose a fatal threat to damaged red blood cells. Oxidative damage also impairs the metabolic mechanisms of red blood cells, leading to a decrease in ATP concentration. Cell membrane damage can also cause denatured hemoglobin to leak from the cell. This free denatured hemoglobin is itself toxic. Free hemoglobin can irreversibly bind to nitric oxide, causing vasoconstriction. The released hemoglobin may form nephrotoxic hemoglobin dimers, leading to kidney damage. /Oxidative hemolysis/
Primaquine (CAS: 90-34-6) is an 8-aminoquinoline antimalarial drug. It is used to prevent relapse of vivax malaria and as a gametocytocide in falciparum malaria. Its mechanism of action is not fully understood but may involve the generation of reactive oxygen species. The compound is essential for malaria eradication efforts due to its unique activity against liver stages and gametocytes. It is also known as 8-(4-Amino-1-methylbutylamino)-6-methoxyquinoline. It is available as an oral medication.

C15H21N3O

259.34674

259.168

90-34-6

Primaquine diphosphate;63-45-6;Primaquine-13C,d3

4908

Viscous liquid

1.1±0.1 g/cm3

451.1±45.0 °C at 760 mmHg

25°C

226.6±28.7 °C

0.0±1.1 mmHg at 25°C

1.616

2.67

2

4

6

19

262

0

N1C2C(=CC(=CC=2NC(CCCN)C)OC)C=CC=1

INDBQLZJXZLFIT-UHFFFAOYSA-N

InChI=1S/C15H21N3O/c1-11(5-3-7-16)18-14-10-13(19-2)9-12-6-4-8-17-15(12)14/h4,6,8-11,18H,3,5,7,16H2,1-2H3

4-N-(6-methoxyquinolin-8-yl)pentane-1,4-diamine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~250 mg/mL (~963.95 mM)

Solubility in Formulation 1: 2.08 mg/mL (8.02 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

 (Please use freshly prepared in vivo formulations for optimal results.)