Disposition of chloroquine in man after single intravenous and oral doses.

Gustafsson, LL; Walker, O; Alván, Gunnar; Beermann, B; Estévez, Francisco; Gleisner, L; Lindström, Björn; Sjöqvist, Folke

doi:10.1111/j.1365-2125.1983.tb01532.x

Cited by 224 publications

(227 citation statements)

References 10 publications

(7 reference statements)

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“…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).…”

Section: General Pharmacokinetic Propertiessupporting

confidence: 93%

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: 93%

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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“…It remains the most widely used antimalarial agent although there is considerable concern surrounding its safety when given parenterally (WHO, 1984). Preliminary studies in volunteers (Gustafsson et al, 1983;Looareesuwan et al, 1986) showed that intravenous injection of chloroquine was potentially dangerous because of transient but very high, plasma chloroquine concentrations. It seemed likely that slow intravenous infusion of chloroquine would be safer.…”

Section: Discussionmentioning

confidence: 99%

“…In both healthy adults (Gustafsson et al, 1983) and children with uncomplicated falciparum malaria (Adelusi et al, 1982;Walker et al, 1983) the drug is well absorbed after oral administration and is detectable in the plasma for up to 52 days and in the urine for up to 119 days following oral or intravenous administration of a single dose (Gustafsson et al, 1983). Slow, rate-controlled intravenous infusion is an acceptable mode of administration for CQ in seriously ill patients or where oral therapy is not possible Edwards et al, 1987).…”

Section: Introduction Methodsmentioning

confidence: 99%

Pharmacokinetics of chloroquine in Thais: plasma and red‐cell concentrations following an intravenous infusion to healthy subjects and patients with Plasmodium vivax malaria.

Edwards¹,

Davies²,

Wattanagoon³

et al. 1988

Brit J Clinical Pharma

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1 Chloroquine diphosphate (15 mg base kg-") was given by constant rate intravenous infusion to two groups of Thai subjects. Eleven were patients with malaria (10 with Plasmodium vivax and one case with Plasmodium malariae) and 10 were healthy normal volunteers. 2 Plasma and packed red-cell concentrations of chloroquine, electrocardiographic intervals, arterial blood pressure and pulse were measured at frequent intervals.3 Peak plasma concentrations at the end of the infusion ranged from 979 to 2,900 ng ml-' in the malaria patients. In the group of healthy subjects the range was 550-2,200 ng ml-'.Values for terminal elimination rate constant, (X,) plasma clearance (CL), initial volume of distribution (V1) and volume of distribution at steady state (Vss) were calculated. For the healthy subjects, mean estimates of these parameters were X, = 0.062 ± 0.030 day-1, CL = 597 ± 238 ml min-, V1 = 0.66 ± 0.71 1 kg-" and Vss = 132 ± 50 1 kg-1For the group of malaria patients, the corresponding values were A, = 0.055 ± 0.032 day-1, CL = 535 ± 246 ml min-1, V1 = 0.74 ± 0.75 1 kg-1 and Vss = 136 ± 64 1 kg-1There was no statistically significant difference in the estimates for any parameter between groups (P -0.05). 4 Chloroquine concentrations in packed red blood cells consistently exceeded those in plasma and showed no consistent change with time throughout the period of study in either group. The median value for the red cell to plasma ratio was between 3 and 4 in each group. Peak red-cell concentrations were significantly higher than the equivalent plasma concentration in both groups. In the malaria patients the range of concentration was 1829-11052 ng ml-'. In the healthy volunteers, the range was 2410-4570 ng ml-'. were not statistically significant. There was no significant difference in the area under the sacked red-cell concentration vs time curve between the malaria patients (151637 + 85737 ng m-1' h) and healthy volunteers (100053 ± 42536 ng ml-1 h), when measured to infinite time.5 Various subjective side effects were reported in all participants. A small but significant fall from baseline systolic blood pressure 105 ± 6 mmHg was recorded, 2 h into the infusion (99 ± 9 mmHg), but baseline values had been regained by the end of the infusion (101 ± 10 mmHg). There was no significant rise in heart rate. However the minimum measured blood pressure and maximum recorded pulse in each subject were significantly different from the resting values. 6 Coincident with changes in blood pressure, there was, in both groups, a significant prolongation of the PR interval, QRS interval (88 ± 13 ms to 101 ± 17 ms) and an increase in T wave height (44 ± 13%). 7 These findings suggest that there are no major differences in the pharmacokinetics of chloroquine between the group of patients with vivax malaria studied here and a matched group of healthy volunteers. The cardiovascular effects of the drug are common to both groups, suggesting that the relationships between the pharmacokinetics of chloroquine are governed principally by the ...

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“…This has been shown clearly for alprenolol and imipramine (Piafsky & Borga, 1977). The high volume of distribution of chloroquine (Gustafsson et al, 1983) indicates extensive tissue binding but it is weakly bound in plasma, 46-74% in healthy individuals. This is in agreement with a previous report by Buchanan & van der Walt (1972).…”

Section: Discussionmentioning

confidence: 99%

Characterization of chloroquine plasma protein binding in man.

Walker¹,

Birkett²,

Alván³

et al. 1983

Brit J Clinical Pharma

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Chloroquine protein binding was determined by equilibrium dialysis of purified plasma proteins and plasma samples from 20 healthy subjects and 14 patients with rheumatoid arthritis. The mean binding was 61 + 9% in plasma from healthy subjects (range 46-74%) and 64 + 7% in plasma from rheumatoid arthritis patients (range 55-79%). Albumin and a,-acid glycoprotein at physiological concentrations bound chloroquine to an approximately equal extent. Protein binding is unlikely to be an important determinant of chloroquine pharmacokinetics or response.

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Disposition of chloroquine in man after single intravenous and oral doses.

Abstract: 1 Chloroquine was given in 300 mg single doses as an i.v. infusion, an oral solution and as tablets at intervals of at least 56 days to 11 healthy volunteers. Concentrations of chloroquine and its metabolite desethylchloroquine were measured in plasma, erythrocytes and urine using h.p.l.c.

Cited by 224 publications

References 10 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

Pharmacokinetics of chloroquine in Thais: plasma and red‐cell concentrations following an intravenous infusion to healthy subjects and patients with Plasmodium vivax malaria.

Characterization of chloroquine plasma protein binding in man.

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