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NOT Open Access | Combination of transdermal patches and solid microneedles for improved transdermal delivery of primaquine

October 20, 2021 - 20:05 -- NOT Open Access
Ananda PWR, Elim D, Zaman HS, Muslimin W, Tunggeng MGR, Permana AD
Int J Pharm. 2021 Oct 16;609:121204

Malaria caused by various types of Plasmodium has become a global health problem. One of the drugs used as the first line of malaria therapy is primaquine (PMQ). PMQ is generally administered through the oral route. However, the use of PMQ orally could potentially cause some side effects and undergo the first-pass metabolism in the liver, reducing its effectiveness. Therefore, it is necessary to develop another drug administration route to avoid this effect. In this study, for the first time, PMQ was formulated into a transdermal patch for transdermal delivery, combined with solid microneedles, Dermaroller®. Following several optimizations, HPMC and glycerin were used as the main polymer and plasticizer, respectively.

NOT Open Access | Improved Liver Delivery of Primaquine by Phospholipid-Free Small Unilamellar Vesicles with Reduced Hemolytic Toxicity

September 23, 2021 - 08:51 -- NOT Open Access
Al Fayez N, Böttger R, Rouhollahi E, Cullis PR, Witzigmann D, Li SD
Mol Pharm. 2021 Sep 21

Hemolytic toxicity caused by primaquine (PQ) is a high-risk condition that hampers the wide use of PQ to treat liver-stage malaria. This study demonstrated that phospholipid-free small unilamellar vesicles (PFSUVs) composed of Tween80 and cholesterol could encapsulate and deliver PQ to the hepatocytes with reduced exposure to the red blood cells (RBCs). Nonionic surfactant (Tween80) and cholesterol-forming SUVs with a mean diameter of 50 nm were fabricated for delivering PQ. Drug release/retention, drug uptake by RBCs, pharmacokinetics, and liver uptake of PFSUVs-PQ were evaluated in in vitro and in vivo models in comparison to free drugs.

Development of weight and age-based dosing of daily primaquine for radical cure of vivax malaria

September 14, 2021 - 14:19 -- Open Access
Walter Robert Taylor, Richard M. Hoglund, Mavuto Mukaka, et al.
Malaria Journal 2021 20:366 9 September 2021

In many endemic areas, Plasmodium vivax malaria is predominantly a disease of young adults and children. International recommendations for radical cure recommend fixed target doses of 0.25 or 0.5 mg/kg/day of primaquine for 14 days in glucose-6-phosphate dehydrogenase normal patients of all ages. However, for many anti-malarial drugs, including primaquine, there is evidence that children have lower exposures than adults for the same weight-adjusted dose. The aim of the study was to develop 14-day weight-based and age-based primaquine regimens against high-frequency relapsing tropical P. vivax.

Dynamics of G6PD activity in patients receiving weekly primaquine for therapy of Plasmodium vivax malaria

September 14, 2021 - 14:07 -- Open Access
Taylor WRJ, Kim S, Kheng S, Muth S, Tor P, Christophel E, Mukaka M, Kerleguer A, Luzzatto L, Baird JK, Menard D
PLoS Negl Trop Dis. 2021 Sep 8;15(9):e0009690

Acute Plasmodium vivax malaria is associated with haemolysis, bone marrow suppression, reticulocytopenia, and post-treatment reticulocytosis leading to haemoglobin recovery. Little is known how malaria affects glucose-6-phosphate dehydrogenase (G6PD) activity and whether changes in activity when patients present may lead qualitative tests, like the fluorescent spot test (FST), to misdiagnose G6PD deficient (G6PDd) patients as G6PD normal (G6PDn). Giving primaquine or tafenoquine to such patients could result in severe haemolysis.

NOT Open Access | Preliminary studies on drug delivery of polymeric primaquine microparticles using the liver high uptake effect based on size of particles to improve malaria treatment

September 8, 2021 - 15:54 -- NOT Open Access
da Silva de Barros AO, Portilho FL, Santos-Oliveira R, et al.
Mater Sci Eng C Mater Biol Appl. 2021 Sep;128:112275

Malaria is the most common parasitic disease around the world, especially in tropical and sub-tropical regions. This parasitic disease can have a rapid and severe evolution. It is transmitted by female anopheline mosquitoes. There is no reliable vaccine or diagnostic test against malaria; instead, Artesunate is used for the treatment of severe malaria and Artemisinin is used for uncomplicated falciparum malaria.

Increased primaquine total dose prevents Plasmodium vivax relapses in patients with impaired CYP2D6 activity: report of three cases

August 18, 2021 - 16:20 -- Open Access
Anielle de Pina-Costa, Ana Carolina Rios Silvino, Edwiges Motta dos Santos, Renata Saraiva Pedro, José Moreira, Gabriela Liseth Umana, Ana Danielle Tavares da Silva, Otília Helena Lupi da Rosa Santos, Karina Medeiros de Deus Henriques, Cláudio Tadeu Daniel-Ribeiro, Patrícia Brasil, Tais Nobrega Sousa and André M. Siqueira
Malaria Journal 2021 20:341, 14 August 2021

The relapsing nature of Plasmodium vivax infection is a major barrier to its control and elimination. Factors such as adequate dosing, adherence, drug quality, and pharmacogenetics can impact the effectiveness of radical cure of P. vivax and need to be adequately evaluated. CYP2D6 pathway mediates the activation of primaquine (primaquine) into an active metabolite(s) in hepatocytes, and impaired activity has been linked to a higher risk of relapse.

Determinants of primaquine and carboxyprimaquine exposures in children and adults with Plasmodium vivax malaria

August 17, 2021 - 16:25 -- Open Access
Chu CS, Watson JA, Phyo AP, Win HH, Yotyingaphiram W, Thinraow S, Soe NL, Aung AA, Wilaisrisak P, Kraft K, Imwong M, Hanpithakpong W, Blessborn D, Tarning J, Proux S, Ling C, Nosten FH, White NJ
Antimicrob Agents Chemother. 2021 Aug 16:AAC0130221

Primaquine is the only widely available drug for radical cure of Plasmodium vivax malaria. There is uncertainty whether the pharmacokinetic properties of primaquine are altered significantly in childhood or not.

Relapse of Plasmodium vivax and Plasmodium ovale malaria with and without primaquine treatment in a non-endemic area

July 6, 2021 - 14:43 -- Open Access
Wångdahl A, Sondén K, Wyss K, Stenström C, Björklund D, Zhang J, Hervius Askling H, Carlander C, Hellgren U, Färnert A
Clin Infect Dis. 2021 Jul 3:ciab610

The effect of primaquine in preventing P. vivax relapses from dormant stages is well established. For P. ovale, the relapse characteristics and the use primaquine is not as well studied. We set to evaluate the relapsing properties of these two species, in relation to primaquine use among imported malaria cases in a non-endemic setting.

Interactions of primaquine and chloroquine with PEGylated phosphatidylcholine liposomes

June 16, 2021 - 15:09 -- Open Access
Miatmoko A, Nurjannah I, Nehru NF, Rosita N, Hendradi E, Sari R, Ekowati J
Sci Rep. 2021 Jun 14;11(1):12420

This study aimed to analyze the interaction of primaquine (PQ), chloroquine (CQ), and liposomes to support the design of optimal liposomal delivery for hepatic stage malaria infectious disease. The liposomes were composed of hydrogenated soybean phosphatidylcholine, cholesterol, and distearoyl-sn-glycero-3-phosphoethanolamine-N-(methoxy[polyethyleneglycol]-2000), prepared by thin film method, then evaluated for physicochemical and spectrospic characteristics. The calcein release was further evaluated to determine the effect of drug co-loading on liposomal membrane integrity.

Evaluation of the effect of supervised anti-malarial treatment on recurrences of Plasmodium vivax malaria

June 16, 2021 - 13:11 -- Open Access
Kelry Mazurega Oliveira Dinelly, Sheila Vitor-Silva, Gisely Cardoso Melo, et al.
Malaria Journal 2021 20:266, 13 June 2021

Relapses in vivax malaria have posed great challenges for malaria control, and they also account for a great proportion of reported cases. Knowing the real effectiveness of a 7-day primaquine (PQ) scheme is crucial in order to evaluate not only the cost-effectiveness of implementing new anti-hypnozoite drugs, but also how health education strategies can guarantee better compliance and be reinforced. This study aimed to evaluate the effect of daily treatment with chloroquine and PQ supervised by health workers versus prescription without supervision.


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