Primaquine in vivax malaria: an update and review on management issues

Fernando, Deepika; Rodrigo, Chaturaka; Rajapakse, Senaka

doi:10.1186/1475-2875-10-351

Cited by 134 publications

(126 citation statements)

References 79 publications

(103 reference statements)

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“…In a review of more than 300 studies publishedbetween 1920 and 2010 regarding P. vivax relapse rates in patients with and without radical treatment, a total of ~17,000 (19.5%) relapses were reported in over 87,000 patients with acute P. vivax malaria, and the relapse rate ranged from zero to 100% [34]. Primaquine is the only licensed medicine for the treatment of P. vivax hypnozoites [20]. Moreover, the transmissible stages of P. falciparum (i.e., gametocytes) are sensitive to primaquine [35].…”

Section: Discussionmentioning

confidence: 99%

“…Primaquine is an important medication for case management, whether it is P. vivax or P. falciparum malaria. It is the only drug that is active against the relapsing forms of P. vivax [20] and also has a gametocidal effect on P. falciparum [21]. However, one of the major drawbacks in primaquine administration is that it can trigger hemolytic reactions in patients with G6PD deficiency.…”

Section: Introductionmentioning

confidence: 99%

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Prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in southeast Iran: implications for malaria elimination

Tabatabaei

Khorashad

Sakeni

et al. 2015

J Infect Dev Ctries

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Introduction: Glucose-6-phosphate dehydrogenase deficiency (G6PD) is an X-linked genetic disorder with a relatively high frequency in malaria-endemic regions. It is an obstacle to malaria elimination, as primaquine administered in the treatment of malaria can cause hemolysis in G6PD-deficient individuals. This study presents information on the prevalence of G6PD deficiency in Sistan and Balouchetsan province, which hosts more than 90% of Plasmodium vivax malaria cases in Iran. This type of information is needed for a successful malaria elimination program. Methodology: A total of 526 students were randomly recruited through schools located in southeast Iran. Information was collected by interviewing the students using a structured questionnaire. Blood samples taken on filter papers were examined for G6PD deficiency using the fluorescent spot test. Results: Overall, 72.8% (383/526) of the subjects showed normal G6PD enzyme function. Mild and severe G6PD deficiency was observed in 14.8% (78) and 12.2% (64) of subjects, respectively. A total 193/261 males (73.9%) and 190/265 (72%) females had normal enzyme activity. Mild G6PD deficiency was observed in 10.8% (28) and 18.9% (50) of male and female subjects, respectively. However, in comparison with females, a greater proportion of males showed severe enzyme deficiency (15.3% versus 9.1%). All these differences were statistically significant (p < 0.006). Conclusions: G6PD deficiency is highly prevalent in southeast Iran. G6PD-deficient individuals are susceptible to potentially severe and lifethreatening hemolytic reactions after primaquine treatment. In order to achieve malaria elimination goals in the province, G6PD testing needs to be made routinely available within the health system.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in southeast Iran: implications for malaria elimination

Tabatabaei

Khorashad

Sakeni

et al. 2015

J Infect Dev Ctries

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“…It is also used as a prophylactic drug against all major forms of human malaria and in combination with clindamycin for the treatment as well as prophylaxis of Pneumocystis pneumonia in human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients (Tekwani and Walker, 2006;Kim et al, 2009). The utility of PQ has also been shown in the prevention and blocking of transmission of Plasmodium falciparum malaria (Hill et al, 2006;White et al, 2012), and recently its use has been proposed as a key strategy in malaria control and elimination efforts (White, 2008;Fernando et al, 2011;John et al, 2012;Galappaththy et al, 2013). However, the therapeutic utility of PQ is limited because of its due to severe hemolytic toxicity in individuals with glucose 6-phosphate dehydrogenase deficiency (Youngster et al, 2010;Baird, 2012;Ganesan et al, 2012;Howes et al, 2013) Synthesis and testing of many different 8-AQs in the 1940s led to the discovery of PQ, with its 4-amino-1-methylbutyl side chain ( Fig.…”

Section: Introductionmentioning

confidence: 99%

Enantioselective Pharmacokinetics of Primaquine in Healthy Human Volunteers

et al. 2015

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Primaquine (PQ), a racemic drug, is the only treatment available for radical cure of relapsing Plasmodium vivax malaria and blocking transmission of P. falciparum malaria. Recent studies have shown differential pharmacologic and toxicologic profiles of individual PQ enantiomers in rodent, dog, and primate animal models. This study was conducted in six healthy adult human volunteers to determine the plasma pharmacokinetic profile of enantiomers of PQ and carboxyprimaquine (cPQ), the major plasma metabolite. The individuals were orally administered PQ diphosphate, equivalent to 45-mg base, 30 minutes after a normal breakfast. Blood samples were collected at different time intervals, and plasma samples were analyzed for enantiomers of PQ and cPQ. Plasma PQ concentrations were low and variable for both parent enantiomers and peaked around 2-4 hours. Peak (2)-(R)-PQ concentrations ranged from 121 ng/ml to 221 ng/ml, and peak (+)-(S)-PQ concentrations ranged from 168 ng/ml to 299 ng/ml. The cPQ concentrations were much higher and were surprisingly consistent from subject to subject. Essentially all the cPQ detected in plasma was (2)-cPQ. The peak concentrations of (2)-cPQ were observed at 8 hours (range: 1104-1756 ng/ml); however, very high concentrations were sustained through 24 hours. (+)-cPQ was two orders of magnitude lower than (2)-cPQ, and in a few subjects it was detected but only under the limit of quantification. In vitro studies with primary human hepatocytes also suggested more rapid metabolism of (2)-PQ compared with (+)-PQ. The results suggest more rapid metabolism of (2)-PQ to (2) cPQ compared with (+)-PQ. Alternatively, (+)-PQ or (+)-cPQ could be rapidly converted to another metabolite(s) or distributed to tissues. This is the first clinical report on enantioselective pharmacokinetic profiles of PQ and cPQ and supports further clinical evaluation of individual PQ enantiomers.

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“…Although its mechanism of action is not yet fully understood, 5 it is thought to interfere with the cellular respiration of the parasite by generating oxygen free radicals and deregulating the electron transport. 6 PQ is a tissue schizonticide 8-aminoquinoline group of drug that destroys exoerythrocytes and hypnozoites in the liver, 7 thus preventing relapse and recrudescence. However, the drug has serious side effects including nausea, vomiting, stomach cramps, and hemolytic anemia.…”

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confidence: 99%

Preparation, characterization, and optimization of primaquine-loaded solid lipid nanoparticles

Omwoyo¹,

Ogutu²,

Oloo³

et al. 2014

IJN

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Primaquine (PQ) is one of the most widely used antimalarial drugs and is the only available drug that combats the relapsing form of malaria. PQ use in higher doses is limited by severe tissue toxicity including hematological- and gastrointestinal-related side effects. Nanoformulation of drugs in an appropriate drug carrier system has been extensively studied and shown to have the potential to improve bioavailability, thereby enhancing activity, reducing dose frequency, and subsequently reducing toxicity. The aim of this work was to design, synthesize, and characterize PQ-loaded solid lipid nanoparticles (SLNs) (PQ-SLNs) as a potential drug-delivery system. SLNs were prepared by a modified solvent emulsification evaporation method based on a water-in-oil-in-water (w/o/w) double emulsion. The mean particle size, zeta potential, drug loading, and encapsulation efficiency of the PQ-SLNs were 236 nm, +23 mV, 14%, and 75%, respectively. The zeta potential of the SLNs changed dramatically, from −6.54 mV to +23.0 mV, by binding positively charged chitosan as surface modifier. A spherical morphology of PQ-SLNs was seen by scanning electron microscope. In vitro, release profile depicted a steady drug release over 72 hours. Differential scanning calorimeter thermograms demonstrated presence of drug in drug-loaded nanoparticles along with disappearance of decomposition exotherms, suggesting increased physical stability of drug in prepared formulations. Negligible changes in characteristic peaks of drug in Fourier transform infrared spectra indicated absence of any interaction among the various components entrapped in the nanoparticle formulation. The nanoformulated PQ was 20% more effective as compared with conventional oral dose when tested in Plasmodium berghei -infected Swiss albino mice. This study demonstrated an efficient method of forming a nanomedicine delivery system for antimalarial drugs.

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Primaquine in vivax malaria: an update and review on management issues

Cited by 134 publications

References 79 publications

Prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in southeast Iran: implications for malaria elimination

Prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in southeast Iran: implications for malaria elimination

Enantioselective Pharmacokinetics of Primaquine in Healthy Human Volunteers

Preparation, characterization, and optimization of primaquine-loaded solid lipid nanoparticles

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