磷酸伯氨喹

Q1: What is the primary mechanism of action of Primaquine phosphate against malaria?

A1: While the exact mechanism remains unclear, Primaquine phosphate is known for its unique ability to target the dormant liver stage of Plasmodium vivax and Plasmodium ovale infections, called hypnozoites. [] This is crucial in preventing relapses, which are a significant challenge in treating these malaria species. []

Q2: How does Primaquine phosphate exert its anti-malarial effects?

A2: Several hypotheses exist regarding Primaquine phosphate's mechanism:

• Interference with Parasite Mitochondrial Function: It is suggested that Primaquine phosphate disrupts the electron transport chain in parasite mitochondria, ultimately leading to parasitic death. [, ]
• Formation of Reactive Oxygen Species: Primaquine phosphate may generate reactive oxygen species, causing oxidative damage within the parasite. []
• Inhibition of Parasite Nucleic Acid Synthesis: It has been proposed that Primaquine phosphate interferes with the synthesis of DNA and RNA in the parasite. []

Q3: What are the downstream effects of Primaquine phosphate on Plasmodium parasites?

A3: Primaquine phosphate's downstream effects are primarily linked to the proposed mechanisms mentioned above. These effects ultimately lead to the death of the parasite, effectively clearing the liver stage infection and preventing relapse.

Q4: What is the molecular formula and weight of Primaquine phosphate?

A4: The molecular formula of Primaquine phosphate is C15H21N3O·H3PO4. Its molecular weight is 365.3 g/mol.

Q5: Is there any spectroscopic data available for Primaquine phosphate?

A5: Yes, several studies have investigated Primaquine phosphate's spectroscopic properties: * FTIR spectroscopy: Used to identify characteristic functional groups and analyze potential interactions between Primaquine phosphate and excipients in formulations. [, ]* UV-Vis spectroscopy: Employed to assess the stability of Primaquine phosphate under various storage conditions. []

Q6: Does Primaquine phosphate exhibit any catalytic properties?

A6: While Primaquine phosphate is primarily recognized for its antimalarial activity, certain research explores its use as a spectrophotometric reagent for detecting trace amounts of gold. [] This application leverages Primaquine phosphate's ability to undergo oxidation by gold (III) ions in a sulfuric acid medium, forming a colored radical measurable at 550 nm.

Q7: Have there been any computational studies on Primaquine phosphate?

A7: While limited information is available on comprehensive computational modeling of Primaquine phosphate itself, some studies have focused on calculating physical parameters like molecular polarizability, diamagnetic susceptibility, and molecular electron ionization cross-section (Q). [] These parameters have been explored for potential correlations with drug activity, plasma protein binding, bioavailability, and dosage.

Q8: What formulation strategies have been investigated to enhance Primaquine phosphate's stability, solubility, or bioavailability?

A8: Several approaches have been explored to optimize Primaquine phosphate delivery:

• Solid Dispersions: Formulating Primaquine phosphate as a solid dispersion using carriers like mono ammonium glycyrrhizinate pentahydrate has been shown to effectively mask its bitter taste while also enhancing dissolution and potentially improving bioavailability. [, ]
• Nanoparticles: Encapsulating Primaquine phosphate within nanoparticles, such as PLGA nanoparticles and PEGylated galactosylated nano lipid carriers, has shown promise in enhancing drug loading, prolonging drug release, and potentially improving its targeting to the liver. [, ] These strategies aim to improve the drug's therapeutic efficacy and minimize potential side effects.

Q9: What are the key considerations for Safety, Health, and Environment (SHE) regulations concerning Primaquine phosphate?

A9: While the provided excerpts do not explicitly detail SHE regulations, responsible handling and disposal of Primaquine phosphate are crucial due to its potential environmental impacts.

Q10: What is the pharmacokinetic profile of Primaquine phosphate?

A10: Primaquine phosphate exhibits a relatively short half-life, necessitating frequent administration and potentially contributing to adverse effects and patient non-compliance. [] Various studies highlighted the pharmacokinetic properties of Primaquine phosphate:

• Absorption and Metabolism: Primaquine phosphate is well-absorbed after oral administration, and its metabolism involves the cytochrome P450 enzyme, particularly CYP2D6. []
• Bioavailability and Distribution: Studies have explored methods to improve Primaquine phosphate's bioavailability and target its delivery to the liver, the primary site of hypnozoite residence. []
• Excretion: The drug and its metabolites are primarily excreted in the urine. []

Q11: What is the relationship between Primaquine phosphate's pharmacokinetics and its pharmacodynamics?

A11: Research indicates a link between impaired CYP2D6 activity and decreased efficacy of Primaquine phosphate in achieving radical cure for P. vivax malaria. [] Individuals with compromised CYP2D6 activity, either due to genetic variations or drug interactions, may experience a higher risk of relapse.

Q12: What evidence supports the in vitro and in vivo efficacy of Primaquine phosphate?

A12: * In vitro: Studies demonstrate Primaquine phosphate's efficacy against Toxoplasma gondii tachyzoites in vitro, inhibiting their growth at specific concentrations. []* In vivo: In animal models, specifically Plasmodium berghei-infected mice, Primaquine phosphate formulated as solid lipid nanoparticles exhibited enhanced effectiveness compared to conventional oral doses. [] This highlights the potential of nanoformulations in improving the drug's therapeutic index.

Q13: What are the known mechanisms of resistance to Primaquine phosphate?

A13: While the precise mechanisms of resistance to Primaquine phosphate are not fully understood, they are thought to involve alterations in parasite drug uptake, drug target modifications, or enhanced detoxification pathways. []

Q14: Is there evidence of cross-resistance between Primaquine phosphate and other antimalarials?

A14: Although the provided excerpts do not directly address cross-resistance, it's a concern with antimalarial drugs. The emergence of resistance to one antimalarial can potentially reduce the efficacy of others with similar mechanisms of action.

Q15: What are the known toxicological effects and safety concerns associated with Primaquine phosphate?

A15: Primaquine phosphate can cause hemolytic anemia, particularly in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. [, , , ] Screening for G6PD deficiency before Primaquine phosphate administration is crucial to prevent this serious adverse effect. []

Q16: What drug delivery strategies have been explored to improve Primaquine phosphate's targeting to the liver?

A16: Researchers are investigating nanocarriers, like galactose-anchored gelatin nanoparticles, to specifically deliver Primaquine phosphate to the liver. [] This approach exploits the asialoglycoprotein receptor expressed on hepatocytes for targeted drug delivery.

Q17: Are there any biomarkers associated with Primaquine phosphate efficacy or toxicity?

A17: CYP2D6 genotype and phenotype can serve as biomarkers to predict the efficacy of Primaquine phosphate. Impaired CYP2D6 activity is linked to a higher relapse risk, indicating potential treatment failure. [] G6PD deficiency is a crucial biomarker for Primaquine phosphate-induced hemolytic anemia. [, , , ]

Q18: What analytical techniques are commonly employed in Primaquine phosphate research?

A18: Several analytical methods are crucial in Primaquine phosphate research:* High-Performance Liquid Chromatography (HPLC): A primary technique for quantitative determination of Primaquine phosphate in various matrices, including tablets, biological samples, and formulations. [, , , ]* Spectrophotometry: Employed to determine Primaquine phosphate concentrations by measuring the absorbance of colored complexes formed with specific reagents. [, , , ]* Dissolution Testing: Used to evaluate the release rate of Primaquine phosphate from various formulations, such as tablets, and assess how different factors impact its dissolution profile. []

Q19: Are there any viable alternatives or substitutes for Primaquine phosphate in treating malaria?

A19: While Primaquine phosphate remains a crucial drug for preventing relapse in specific malaria species, researchers are exploring alternative therapies: * Tafenoquine: A single-dose 8-aminoquinoline antimalarial drug with a longer half-life than Primaquine phosphate, potentially improving patient adherence. []