Pharmacokinetics and Efficacy of Piperaquine and Chloroquine in Melanesian Children with Uncomplicated Malaria

Abstract

The disposition of chloroquine (CQ) and the related 4-aminoquinoline, piperaquine (PQ), were compared in Papua New Guinean children with uncomplicated malaria. Twenty-two children were randomized to 3 days of PQ phosphate at 20 mg/kg/day (12 mg of PQ base/kg/day) coformulated with dihydroartemisinin (DHA-PQ), and twenty children were randomized to 3 days of CQ at 10 mg base/kg/day with a single dose of sulfadoxinepyrimethamine (CQ-SP). After a 42-day intensive sampling protocol, PQ, CQ, and its active metabolite monodesethyl-chloroquine (DECQ) were assayed in plasma by using high-performance liquid chromatography. A two-compartment model with first-order absorption was fitted to the PQ and CQ data. There were no significant differences in age, gender, body weight, or admission parasitemia between the two groups. The PCR-corrected 42-day adequate clinical and parasitological responses were 100% for DHA-PQ and 94% for CQ-SP, but P. falciparum reinfections during follow-up were common (33 and 18%, respectively).

An HPLC method with diode array detector for the simultaneous quantification of chloroquine and desethylchloroquine in plasma and whole blood samples from Plasmodium vivax patients in Vietnam, using quinine as an internal standard

“…In general, large inter‐individual differences of CQ and MCQ levels were found in plasma as well as in whole blood, in agreement with previous publications (Dua et al , 1999; Karunajeewa et al , 2008, 2010; Sutanto et al , 2010). All 14 subjects had CQ blood levels on day 7 of between 196 and 855 ng/mL, over the concentration of 100 ng/mL that is considered chloroquine‐resistant P. vivax .…”

“…Moreover, it was successfully achieved with a smaller sample volume of 100 μL vs. 150 μL (Cheomung and Na‐Bangchang, 2011), 200 μL (Bustos et al , 2002), 500 μL (Dua et al , 1999; Zuluaga‐Idárraga et al , 2014) and 1000 μL (Chaulet et al , 1994; Deng et al , 2006; Karunajeewa et al , 2008, 2010; Yakasai, 2006) in previous studies. However, when CQ and MCQ analysis was performed by LC‐MS/MS, the LOQ was 7.5 ng/mL for CQ using 200 μL plasma (Hodel et al , 2009), 0.5 ng/mL for MCQ and 1.0 ng/mL for CQ (Tang and Sojinu, 2012), and 0.2 ng/mL for CQ and 0.4 ng/mL for MCQ using 100 μL plasma (Boonprasert et al , 2012).…”

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

“…A two-compartment model was best fit with the concentration-time profiles of both CQ and DECQ, with a one transit compartment model for the absorption of CQ. This multiexponential decline in blood concentrations of both CQ and DECQ were in consistency with previous reports (Gustafsson et al, 1983;Aderounmu et al, 1986;Karunajeewa et al, 2008;Obua et al, 2008). The mean transit time of absorption (MTT: 0.773 h), peripheral volume of distribution (Vp: 1,600 l), and elimination halflife (t 1/2 : 10.7 days) of CQ were similar to the previously reported values in other populations, but systemic clearance (CL: 6.13 l/h) was relatively lower (FriskHolmberg et al, 1984;Aderounmu et al, 1986;Gustafsson et al, 1987;Tett et al, 1987;Edwards et al, 1988;Titus et al, 1989;Vries et al, 1994;Lee et al, 2008;Karunajeewa et al, 2008;Obua et al, 2008;Karunajeewa et al, 2010;Wetsteyn et al, 2012;Zhao et al, 2014).…”

pfmdr1 Amplification Is Related to Increased Plasmodium falciparum In Vitro Sensitivity to the Bisquinoline Piperaquine

“…This, associated with the knowledge that PPQ resistance has already emerged in the past (13), commands urgency regarding the research of its molecular mechanisms. Additionally, it should be noted that emerging drug resistance has even been suggested as an explanation for an unexpected low cure rate of the DHA-PPQ ACT in a clinical trial conducted in Papua New Guinea (18).…”