Published Studies Related to Primaquine
Directly-observed therapy (DOT) for the radical 14-day primaquine treatment of Plasmodium vivax malaria on the Thai-Myanmar border. [2010.11.01]
BACKGROUND: Plasmodium vivax has a dormant hepatic stage, called the hypnozoite, which can cause relapse months after the initial attack. For 50 years, primaquine has been used as a hypnozoitocide to radically cure P. vivax infection, but major concerns remain regarding the side-effects of the drug and adherence to the 14-day regimen. This study examined the effectiveness of using the directly-observed therapy (DOT) method for the radical treatment of P. vivax malaria infection, to prevent reappearance of the parasite within the 90-day follow-up period. Other potential risk factors for the reappearance of P. vivax were also explored... CONCLUSIONS: Adherence to the 14-day primaquine regimen is important for the radical cure of P. vivax malaria infection. Implementation of DOT reduces the reappearance rate of the parasite, and may subsequently decrease P. vivax transmission in the area.
In Tanzania, hemolysis after a single dose of primaquine coadministered with an artemisinin is not restricted to glucose-6-phosphate dehydrogenase-deficient (G6PD A-) individuals. [2010.05]
The current interest in malaria elimination has led to a renewed interest in drugs that can be used for mass administration to minimize malaria transmission. Primaquine (PQ) is the only generally available drug with a strong activity against mature Plasmodium falciparum gametocytes, the parasite stage responsible for transmission...
A comparison of two short-course primaquine regimens for the treatment and radical cure of Plasmodium vivax malaria in Thailand. [2010.04]
Thai adult males (N = 85) with acute Plasmodium vivax malaria and normal glucose-6-phosphate dehydrogenase screening were randomized to receive 30 mg or 60 mg primaquine daily for 7 days (N = 43 and 42, respectively). The regimens were well tolerated and all patients recovered fully... A 1 week course of primaquine 60 mg daily is an effective treatment of vivax malaria in this region.
Therapeutic efficacy of chloroquine and chloroquine plus primaquine for the treatment of Plasmodium vivax in Ethiopia. [2010.02]
Plasmodium vivax is the second most important cause of morbidity in Ethiopia. There is, however, little information on P.
[Therapeutic efficacy of a regimen of artesunate-mefloquine-primaquine treatment for Plasmodium falciparum malaria and treatment effects on gametocytic development] [2009.06]
INTRODUCTION: The treatment of Plasmodium falciparum malaria requires a safe and effective therapeutic treatment regimen, which in turn has high impact on the transmission. In 2006, an artesunate (AS)-mefloquine (MQ) treatment program was implemented in Antioquia. In addition, primaquine (PQ) was added to eliminate malaria gametocytes in the bloodstream. OBJECTIVE: The efficacy and gametocytocidal activity was evaluated for two treatment regimens, AS-MQ-PQ and AS-MQ, in patients with uncomplicated P. falciparum malaria... CONCLUSION: These studies recommend the use of AS-MQ to treat P. falciparum malaria given its good therapeutic efficacy. However, further assessment is suggested concerning the benefit of adding PQ to this treatment scheme.
Clinical Trials Related to Primaquine
Primaquine Pharmacokinetics in Lactating Women and Their Infants [Recruiting]
The weight of malaria falls most heavily on young children and pregnant women but studies of
the safety of antimalarials in pregnancy and lactation are few. The only recommended
medication used for radical treatment of P. vivax is primaquine. The 2010 WHO malaria
guidelines recommend its use in all patients with P. vivax infection in areas of low
transmission, in the absence of contraindications. Primaquine is contraindicated in
pregnancy. The postpartum period presents a key opportunity to definitively treat women who
suffer multiple malaria relapses during pregnancy. The 2010 WHO malaria treatment guidelines
allow for primaquine use during lactation but there are no studies to date quantifying
primaquine excretion in breast milk and the dose that breastfed infants would be exposed to
is unknown. The investigators propose to study the pharmacokinetics of primaquine in
maternal and infant plasma and in breast milk during a 14 day radical treatment of P. vivax.
Some inferences about the expected behavior of primaquine in lactation can be drawn from its
known pharmacologic properties. Primaquine pharmacokinetics have been well characterized in
healthy subjects and malaria patients after single and multiple oral dosing. Peak
concentrations are reached within 2-3 hours after dosing and the plasma elimination
half-life is ~7 hours. It is extensively distributed in the tissue and largely metabolized
to inert carboxyprimaquine, the major plasma metabolite, which undergoes further
biotransformation to unknown metabolites that are probably more toxic than the parent
compound. The identification of other metabolites in humans has been difficult to pursue
because the expected aminophenol metabolites are unstable.
No pharmacokinetic studies have been done to measure primaquine excretion in breast milk. A
few studies have been done of other antimalarials during lactation and have shown low levels
of drug in breast milk during treatment.
Pharmacokinetic and in Vitro Transmission Blocking Activities Study of Primaquine Compare to Methylene Blue in Healthy Volunteer Both G6PD Normal and G6PD Deficiency [Not yet recruiting]
The emergence of partial artemisinin resistance in Plasmodium falciparum on the
Cambodia-Thai border and more recently on the Myanmar-Thai border jeopardizes the renewed
global efforts of control and elimination of malaria. Containment of this severe threat
requires reduction of transmission of the resistant phenotype by adding gametocytocidal
drugs to the treatment of falciparum malaria. Mathematical models also predict that
transmission blocking will be required if the goal of malaria elimination is to be achieved.
The only drug currently available with strong gametocytocidal properties against the more
mature gametocytes is primaquine. However, the oxidative properties of primaquine readily
causes acute haemolysis in glucose 6 phosphate dehydrogenase (G6PD) deficiency, the degree
of which appears to be inversely related to G6PD enzyme activity. Because of these safety
concerns, primaquine is not widely deployed in treatment regimens for falciparum malaria,
even in areas with documented artemisinin resistance. Methylene blue, which does not exert
its action through an oxidative mechanism, is a promising alternative as a gametocytocidal
adjuvant to artemisinin combination therapies (ACTs). Paul Ehrlich discovered methylene blue
as the first synthetic drug ever to treat malaria. In contrast with primaquine, the
thiazine dye methylene blue asserts its properties as an oxidizing agent only at very high
doses, whereas at pharmacologic doses it has reducing agent properties and is for this
reason used as a medication for the treatment of methemoglobinemia. A recent laboratory
study identified methylene blue as a potent inhibitor of gametocyte development across all
stages, almost fully abolishing P. falciparum transmission to mosquitoes at concentrations
readily achievable in humans. In addition, a recent clinical study in 180 children with
uncomplicated falciparum malaria in Burkina Faso showed that, compared to
artesunate-amodiaquine alone, addition of the cheap drug methylene blue to either artesunate
or amodiaquine importantly reduced gametocyte carrier rates measured at days 3, 7, and 14 of
follow-up. This effect was seen both in patients with and without P. falciparum
gametocytaemia at baseline. The current series of studies will investigate further methylene
blue as a potential gametocytocidal drug in the treatment of uncomplicated falciparum
Evaluation of the Gametocytocidal Efficacy and Safety of Primaquine in Uncomplicated Falciparum Malaria in Uganda [Recruiting]
The purpose of this study is to evaluate the safety and efficacy of lower doses of
primaquine compared to the dose recommended by the WHO for reducing P. falciparum
gametocytes in the infected human host to prevent transmission of falciparum malaria to the
anopheles mosquito vector.
Pharmacokinetic Study of Primaquine and Pyronaridine-Artesunate in Healthy Subjects [Recruiting]
The observed changes of P. falciparum sensitivity to artemisinin lead to the intensification
of early detection as well as treatment monitoring in malaria infection. It is widely
accepted that the development of resistance can be delayed by the use of combination
therapy, especially combinations that include artemisinin derivatives (acts). As the
resistance problem is considered extremely serious; as a consequence, who has recommended
that all monotherapy for malaria should be stopped.
Current WHO guidelines recommend that the drug combination regimens using ACT with effective
partner medicines should be used to decrease the risk of development or spreading of
Phase2a Primaquine Dose Escalation Study [Not yet recruiting]
The purpose of this study is to evaluate the safety, efficacy, and pharmacokinetcis of low
single-dose primaquine for gametocydal activity against P. falciparum among adult G6PD-normal