In the last two years, a substantial increase in the number of malaria vivax
cases has occurred in the Brazilian Amazon basin. The adequate exposure of
hypnozoites to primaquine is a matter of interest as these dormant forms are
responsible for the maintenance or even the increase of malaria burden in
endemic areas. The aim of this study was to estimate the levels of primaquine
and carboxyprimaquine in whole blood samples of patients with P.
vivax treated with chloroquine and an abbreviated regimen of
primaquine (0.5 mg/kg/d for 7 days), with adequate clinical and parasitological
outcomes after 180 days of follow-up. A total of 40 male patients met the
criteria for inclusion in the study. Primaquine and carboxyprimaquine were
measured by high-performance liquid chromatography. The levels of primaquine in
whole blood samples ranged from 40-238 ng/mL, 42-196 ng/mL and 42-150 ng/mL on
days 1, 3 and 7. The levels of carboxyprimaquine in whole blood samples ranged
from 87-234 ng/mL, 96-252 ng/mL and 74-448 ng/mL on days 1, 3 and 7. These data
provide a reliable estimation of exposure of the infecting parasite to
primaquine. Based on the regional pattern of relapse, the estimated blood levels
of primaquine can be considered effective against hypnozoites of the local
circulating strains of P. vivax.
Chloroquine is the first-line therapy against the asexual stages of Plasmodium vivax. There is a high variation of chloroquine plasma levels after therapeutic doses, which can lead to inadequate exposure to the drug. The gender influence was low regarding the disposition of the drug, which is relevant as there are significant physiological variations between male and female patients. The objective of the study was to investigate whether gender modifies the pharmacokinetics parameters of chloroquine in patients with malaria vivax. A prospective study was performed in male and female adult patients using chloroquine (total dose of 25 mg/kg for three days) combined with primaquine. Serial blood samples were collected at admission and up to 672 h post-administration of the drugs. Chloroquine was measured in plasma samples by high-performance liquid chromatography with fluorescence detection. A non-compartmental analysis was used for modeling the data. A total of 26 male and 25 female patients were enrolled in the study. The pharmacokinetic parameters of chloroquine were similar between male and female patients: a half-life of 9.5 days and 10.2 days, maximum concentration (Cmax) of 1295 ng/ml and 1220 ng/ml, area-under-the-curve (AUC 0-28) of 241 µg/mL h and 237 µg/mL h, observed clearance (CL/f) of 5.8 and 5.5 L/h and the volume of distribution (V/f) of 1869 L and 1936 L. The study results suggest that a similar dose regimen of chloroquine combined with primaquine provides a comparable pattern of exposure in male and female patients.
Background
Chloroquine is effective against the asexual blood stage of Plasmodium vivax. A high proportion of children are underdosed with the drug, but there are no studies comparing chloroquine exposure in adults and children aged 8–11 years old. The present study intends to compare these populations using the area under the curve (AUC) derived from the plasma concentration-time profile in patients with P. vivax.
Methods
A prospective study of cases was performed on male children (aged 9–11 years) and adults with vivax malaria. Blood samples were collected after several days of treatment. Chloroquine was measured by high-performance liquid chromatography. A non-compartmental pharmacokinetic model was used to calculate the pharmacokinetic parameters of the drug.
Results
A total of 20 children and 25 adults were included in the study. Plasma concentrations of chloroquine in older children ranged from 67 to 1112 ng/ml, and in adults the value ranged from 74 to 1147 ng/ml. The AUC to the last measurable concentration and to infinite was significantly lower in children than in adults, indicating a lower exposure to the drug.
Conclusion
These data demonstrate lower exposure to chloroquine in children, which corroborates the importance of optimising the doses of chloroquine in the study age band to ensure adequate exposure to the drug.
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