Abstract
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. Co-administration 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 co-administered 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. Key words: Malaria, pharmacokinetics, chloroquine, primaquine, Thai population.
Highlights
Malaria remains a major public health problem in many countries of the world
The current 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
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’ glucose-6-phosphate dehydrogenase (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 (Edwards et al, 1993; Na-Bangchnag et al, 1994b; Hanboonkunpakarn et al, 2014; Jittamala et al, 2015)
Summary
Malaria remains a major public health problem in many countries of the world. Despite the progress in reducing malaria cases and deaths, it is estimated that 212 million cases of malaria occurred worldwide in 2015, leading to. Information of the pharmacokinetics of CQ in patients with malaria is essential for rational and safe intravenous regimens In another two published articles (Na-Bangchang et al, 1994a; Hoglund et al, 2016), the relationship between clinical efficacy of the standard three-day CQ and the pharmacokinetics of CQ and DECQ were examined in patients with P. vivax infection to explain the cause of treatment failure in the light of accumulating evidence for the declining of in vitro sensitivity of P. vivax isolates in Thailand to CQ. The relationship between CQ and DECQ blood concentrations and clinical response following the standard three-day regimen of CQ for treatment of P. vivax infection was investigated in Thai population in the two studies (Na-Bangchang et al, 1994a; Hoglund et al, 2016).
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