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Tese
Estimativas da dose e dos parâmetros farmacocinéticos da cloroquina em pacientes com malária por Plasmodium vivax na amazônia brasileira
Malaria caused by Plasmodium vivax is still an important public health issue in the Brazilian Amazon basin, with 169,000 cases recorded in 2018. The treatment is based on the concurrent administration of chloroquine and primaquine. Despite the efficacy and tolerability over 60 years of use, there...
Autor principal: | FERREIRA, Michelle Valéria Dias |
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Grau: | Tese |
Idioma: | por |
Publicado em: |
Universidade Federal do Pará
2022
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Assuntos: | |
Acesso em linha: |
http://repositorio.ufpa.br:8080/jspui/handle/2011/14092 |
Resumo: |
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Malaria caused by Plasmodium vivax is still an important public health issue in the
Brazilian Amazon basin, with 169,000 cases recorded in 2018. The treatment is
based on the concurrent administration of chloroquine and primaquine. Despite the
efficacy and tolerability over 60 years of use, there are several issues related to
chloroquine uses that should be elucidated in the Brazilian Amazon. The aims of the
present study were to estimate the doses administered and to assess the
pharmacokinetics parameters of chloroquine by a no-compartmental approach
associating with patients age and gender. A prospective study of cases was carried
out in the municipality of Anajas, PA, with 161 patients diagnosed with malaria
caused by P. vivax, 81 children and 80 adults. The geometric mean of parasites at
admission were 2,644 in children and 1,210 per mm3 of blood in adults. Parasites
were cleared from the peripheral blood within 28 days. The doses of chloroquine
administered ranged from 20,2 to 28,9 mg/kg in children and 16,3 to 34,09 mg/kg in
adults. The proportions of patients with chloroquine doses below 25 mg/kg ranged
from 29,4% to 63,6% in children and 59% in adults. The required doses were lower
than the given doses in ages ranges of 4-8 years (U=64; p=0,007), 9-11 years (U=32;
p<0,001) and 12-14 years (U=18; p<0,0001). Blood chloroquine concentrations in
168h in ng/ml ranged from 107 to 440 in children and 201 to 582 in adults. Blood
levels of desethylchloroquine ranged from 167 to 412 in children and 178 to 482 in
adults. The pharmacokinetics parameters derived from no-compartmental approach
were elimination rate constant, area under the curve at day 28, extrapolated to
infinite, maximum concentration, total clearance, elimination half-life, volume of
distribution and meantime of residence. Overall, the data were similar to those found
in other population groups and confirmed the high elimination half-life and a large
volume of distribution of the drug. There was no significant influence of gender, but
the age decreased significantly the clearance and the volume of distribution. The
results permit to conclude that chloroquine is yet effective in the research area. Most
of the patients received sub-doses of chloroquine. The pharmacokinetics parameters
were not influenced by gender, but the age promoted a significant decrease in the
volume of distribution and in the clearance, with the lower values in children. |