Pharmacokinetics of primaquine in man. II. Comparison of acute vs chronic dosage in Thai subjects.

Ward, SA; Mihaly, G W; Edwards, Geoffrey; Looareesuwan, S; Phillips, R E; Chanthavanich, Pornthep; Warrell, D. A.; Orme, ML; Breckenridge, AM

doi:10.1111/j.1365-2125.1985.tb02710.x

Cited by 55 publications

(31 citation statements)

References 11 publications

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“…Pre-treatment with CQ did not significantly alter the pharmacokinetics of PQ despite the relatively high systemic exposure of CQ (approximately 500 to 3,000 ng/ml) (Na-Bangchang et al, 1994a; Hoglund et al, 2016). The PQ pharmacokinetics in G6PD-deficient patients with P. vivax malaria was in broad agreement with other reports (Greaves et al, 1980;Fletcher et al, 1981;Mihly et al, 1985;Ward et al, 1985;Bhatia et al, 1986;NaBangchang et al, 1994b). After absorption from gastrointestinal tract, the drug rapidly declined monoexponentially with complete elimination within 24 h of dosing.…”

Section: General Pharmacokinetic Propertiessupporting

confidence: 81%

“…A significant increase in total clearance of PQ was found following the last dose leading to the observed lower AUC and C max compared with that after the first dose (Table 2). These findings were in contrast with the previously described studies by Mihaly et al (1985), Greaves et al (1980), andWard et al (1985) in which similar total body clearance with no accumulation of PQ was found after multiple dose administration of 15 mg PQ. The pre-dose plasma PQ concentrations at steady in this study varied from 0 to 35 ng/ml while Greaves et al (1980) reported undetectable level.…”

Section: Referencecontrasting

confidence: 57%

“…This review summarizes findings of the nine pharmacokinetic investigations in relation to the four main issues (Table 2), that is the pharmacokinetic change following multiple dosing of PQ (Greaves et al, 1980;Fletcher et al, 1981;Ward et al, 1985;Singhasivanon et al, 1991), the relationship between patients' G6PD status and PQ and/or CPQ pharmacokinetics (Greaves et al, 1980;Fletcher et al, 1981;Na-Bangchang et al, 1994), the influence of the acute phase malaria infection on pharmacokinetics of PQ, and the pharmacokinetic interactions between PQ and the concurrently administered antimalarial drugs (quinine, chloroquine, mefloquine, dihydroartemisinin-piperaquine, pyronaridine, and artesunate) (Edwards et al, 1993;Na-Bangchnag et al, 1994b;Hanboonkunpakarn et al, 2014;Jittamala et al, 2015). The first human PQ pharmacokinetic was reported almost concurrently by Greaves et al (1980) and Fletcher et al (1981).…”

Section: General Pharmacokinetic Propertiesmentioning

confidence: 99%

“…The observed systemic clearance was similar to that reported in healthy Thai and Caucasian subjects (Greaves et al, 1980;Mihaly et al, 1985;Fletcher et al, 1981). The potential of PQ to alter its own disposition, and in addition, accumulation of plasma concentrations of the carboxylic acid metabolite CPQ during repeated dosing was further investigated in 5 healthy Thai male subjects by Ward et al (1985) at Trang Provincial Hospital, southern Thailand. The study design was a crossover design in which each subject received PQ on two occasions, that is a single oral dose of 15 mg (base) PQ on the first occasion and repeated oral dose of 15 mg (base) daily for 14 days (no information on pharmaceutical formulation of PQ provided).…”

Section: Referencementioning

confidence: 99%

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A review of clinical pharmacokinetics of chloroquine and primaquine and their application in malaria treatment in Thai population

Chukanchitipat¹,

Na‐Bangchang²

2017

Afr. J. Pharm. Pharmacol.

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The blood schizontocidal chloroquine (CQ) and the tissue schizontocidal and gametocytocidal primaquine (PQ) remain the mainstay treatment of Plasmodium vivax and Plasmodium ovale infections for more than six decades. The review focuses on the clinical pharmacokinetic studies of both drugs in Thai population that have provided useful information for clinical application in the treatment of malaria. There appears to be no major differences in the pharmacokinetics of both drugs with respect to the influences of ethinicity, acute phase malaria infection, and G6PD status. The increase in systemic exposure of CQ and/or its metabolite mono-desethylchlorooquine (DECQ) following oral administration could be due to change in the absorption kinetics during acute phase infection. The high clinical efficacy of CQ for treatment of P. vivax infection in Thailand supports this benefitial pharmacokinetic change. Transiently high and toxic plasma/whole blood concentrations of CQ following intravenous infusion at high rate is explained by the pharmacokinetic characteristics of CQ. Pharmacokinetics of PQ following repeated dosing in most studies appears to be similar to that following a single dosing. This suggests that auto-inhibition of PQ metabolism during multiple dosing is unlikely. Coadministration of CQ, dihydroartemisinin-piperaquine (DHA-PIP), and pyronaridine-artesunate (PYR-ARS) significantly altered the pharmacokinetics of PQ. In the presence of these drugs, PQ exposure was significantly increased. The apparent volume of distribution of PQ was reduced when coadministered with PYR-ARS. In addition, plasma concentrations of CPQ were significantly increased in the presence of CQ. Clinical relevance of these interactions needs to be confirmed.

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Section: General Pharmacokinetic Propertiessupporting

confidence: 81%

Section: Referencecontrasting

confidence: 57%

Section: General Pharmacokinetic Propertiesmentioning

confidence: 99%

Section: Referencementioning

confidence: 99%

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A review of clinical pharmacokinetics of chloroquine and primaquine and their application in malaria treatment in Thai population

Chukanchitipat¹,

Na‐Bangchang²

2017

Afr. J. Pharm. Pharmacol.

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“…Because it has an elimination half-life of 4 to 6 h (32), there is no significant PMQ accumulation with daily dosing. Therefore, the C max and area under the plasma concentration-time curve at the beginning and end of a 14-day course of daily PMQ doses are similar (1,33). This lack of time/dose-dependent kinetics improves the validity of extrapolation from single to multiple dosings in our simulations.…”

Section: Figmentioning

confidence: 68%

Pharmacokinetic Properties of Single-Dose Primaquine in Papua New Guinean Children: Feasibility of Abbreviated High-Dose Regimens for Radical Cure of Vivax Malaria

Moore

Salman

Benjamin

et al. 2014

Antimicrob Agents Chemother

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f Since conventional 14-day primaquine (PMQ) radical cure of vivax malaria is associated with poor compliance, and as total dose, not therapy duration, determines efficacy, a preliminary pharmacokinetic study of two doses (0.5 and 1.0 mg/kg of body weight) was conducted in 28 healthy glucose-6-phosphate dehydrogenase-normal Papua New Guinean children, aged 5 to 12 years, to facilitate development of abbreviated high-dose regimens. Dosing was with food and was directly observed, and venous blood samples were drawn during a 168-h postdose period. Detailed safety monitoring was performed for hepatorenal function and hemoglobin and methemoglobin concentrations. Plasma concentrations of PMQ and its metabolite carboxyprimaquine (CPMQ) were determined by liquid chromatography-mass spectrometry and analyzed using population pharmacokinetic methods. The derived models were used in simulations. Both single-dose regimens were well tolerated with no changes in safety parameters. The mean PMQ central volume of distribution and clearance relative to bioavailability (200 liters/70 kg and 24.6 liters/ h/70 kg) were within published ranges for adults. The median predicted maximal concentrations (C max ) for both PMQ and CPMQ after the last dose of a 1.0 mg/kg 7-day PMQ regimen were approximately double those at the end of 14 days of 0.5 mg/kg daily, while a regimen of 1.0 mg/kg twice daily resulted in a 2.38 and 3.33 times higher C max for PMQ and CPMQ, respectively. All predicted median C max concentrations were within ranges for adult high-dose studies that also showed acceptable safety and tolerability. The present pharmacokinetic data, the first for PMQ in children, show that further studies of abbreviated high-dose regimens are feasible in this age group. P rimaquine (PMQ) is an 8-aminoquinoline drug used for primary (causal) and terminal malaria prophylaxis, radical cure of Plasmodium vivax and P. ovale, and as a gametocytocidal agent in P. falciparum infections (1-4). It remains the only FDA-approved drug for elimination of liver stages (hypnozoites and schizonts) of P. vivax and P. ovale (2,4,5). In many non-African tropical countries, such as Papua New Guinea (PNG), there is hyperendemic transmission of P. vivax (5-7). Children carry the burden of repeated P. vivax infections in this geoepidemiologic setting (5,8,9). Therefore, a safe and effective radical cure would benefit personal well-being, growth, and development and lessen the economic impact of the infection on the community (10).Primaquine is conventionally administered as a 14-day course for terminal prophylaxis and radical cure (2), but this regimen can be problematic due to poor compliance (1, 5). An abbreviated regimen would have advantages (11, 12) as long as it was safe and well tolerated. Pharmacokinetic studies of PMQ to date have been conducted only in adults (6). As the pharmacokinetic and pharmacodynamic profiles of antimalarial drugs can differ between adults and children (13), there is a need for a study of PMQ disposition in the pediatric age grou...

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Synthesis of [¹³C₆]primaquine

Herath

McChesney

Walker

et al. 2013

Labelled Comp Radiopharmac

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Pharmacokinetics of primaquine in man. II. Comparison of acute vs chronic dosage in Thai subjects.

Cited by 55 publications

References 11 publications

A review of clinical pharmacokinetics of chloroquine and primaquine and their application in malaria treatment in Thai population

A review of clinical pharmacokinetics of chloroquine and primaquine and their application in malaria treatment in Thai population

Pharmacokinetic Properties of Single-Dose Primaquine in Papua New Guinean Children: Feasibility of Abbreviated High-Dose Regimens for Radical Cure of Vivax Malaria

Synthesis of [¹³C₆]primaquine

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Pharmacokinetics of primaquine in man. II. Comparison of acute vs chronic dosage in Thai subjects.

Cited by 55 publications

References 11 publications

A review of clinical pharmacokinetics of chloroquine and primaquine and their application in malaria treatment in Thai population

A review of clinical pharmacokinetics of chloroquine and primaquine and their application in malaria treatment in Thai population

Pharmacokinetic Properties of Single-Dose Primaquine in Papua New Guinean Children: Feasibility of Abbreviated High-Dose Regimens for Radical Cure of Vivax Malaria

Synthesis of [13C6]primaquine

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Synthesis of [¹³C₆]primaquine