Determinants of primaquine and carboxyprimaquine exposures in children and adults with Plasmodium vivax malaria
<strong>Background</strong> Primaquine is the only widely available drug for radical cure of Plasmodium vivax malaria. There is uncertainty whether the pharmacokinetic properties of primaquine are altered significantly in childhood or not. <br> <strong>Methods</strong>...
| Auteurs principaux: | , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Langue: | English |
| Publié: |
American Society for Microbiology
2021
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| _version_ | 1826268307057016832 |
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| author | Chu, CS Watson, JA Phyo, AP Win, HH Yotyingaphiram, W Thinraow, S Soe, NL Aung, AA Wilaisrisak, P Kraft, K Imwong, M Hanpithakpong, W Blessborn, D Tarning, J Proux, S Ling, C Nosten, FH White, NJ |
| author_facet | Chu, CS Watson, JA Phyo, AP Win, HH Yotyingaphiram, W Thinraow, S Soe, NL Aung, AA Wilaisrisak, P Kraft, K Imwong, M Hanpithakpong, W Blessborn, D Tarning, J Proux, S Ling, C Nosten, FH White, NJ |
| author_sort | Chu, CS |
| collection | OXFORD |
| description | <strong>Background</strong>
Primaquine is the only widely available drug for radical cure of Plasmodium vivax malaria. There is uncertainty whether the pharmacokinetic properties of primaquine are altered significantly in childhood or not.
<br>
<strong>Methods</strong>
Glucose-6-phosphate dehydrogenase normal patients with uncomplicated P. vivax malaria were randomized to receive either chloroquine (25mg base/kg) or dihydroartemisinin-piperaquine (dihydroartemisinin 7mg/kg and piperaquine 55mg/kg) plus primaquine; given either as 0.5 mg base/kg/day for 14 days or 1 mg/kg/day for 7 days. Pre-dose day 7 venous plasma concentrations of chloroquine, desethylchloroquine, piperaquine, primaquine and carboxyprimaquine were measured. Methemoglobin levels were measured on day 7.
<br>
<strong>Results</strong>
Day 7 primaquine and carboxyprimaquine concentrations were available for 641 patients. After adjustment for the primaquine mg/kg daily dose, day of sampling, partner drug, and fever clearance, there was a significant non-linear relationship between age and trough primaquine and carboxyprimaquine concentrations, and day methemoglobin levels. Compared to adults 30 years of age, children 5 years of age had trough primaquine concentrations 0.53 (95% CI: 0.39- 0.73) fold lower, trough carboxyprimaquine concentrations 0.45 (95% CI: 0.35- 0.55) fold lower, and day 7 methemoglobin levels 0.87 (95% CI: 0.58-1.27) fold lower. Increasing concentrations of piperaquine and chloroquine and poor metabolizer CYP 2D6 alleles were associated with higher day 7 primaquine and carboxyprimaquine concentrations. Higher blood methemoglobin concentrations were associated with a lower risk of recurrence.
<br>
<strong>Conclusion</strong>
Young children have lower primaquine and carboxyprimaquine exposures, and lower levels of methemoglobinemia, than adults. Young children may need higher weight adjusted primaquine doses than adults. |
| first_indexed | 2024-03-06T21:07:40Z |
| format | Journal article |
| id | oxford-uuid:3d05e85b-7d6b-4a35-91fe-cb57cd3f1fe7 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:07:40Z |
| publishDate | 2021 |
| publisher | American Society for Microbiology |
| record_format | dspace |
| spelling | oxford-uuid:3d05e85b-7d6b-4a35-91fe-cb57cd3f1fe72022-03-26T14:17:09ZDeterminants of primaquine and carboxyprimaquine exposures in children and adults with Plasmodium vivax malariaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3d05e85b-7d6b-4a35-91fe-cb57cd3f1fe7EnglishSymplectic ElementsAmerican Society for Microbiology2021Chu, CSWatson, JAPhyo, APWin, HHYotyingaphiram, WThinraow, SSoe, NLAung, AAWilaisrisak, PKraft, KImwong, MHanpithakpong, WBlessborn, DTarning, JProux, SLing, CNosten, FHWhite, NJ<strong>Background</strong> Primaquine is the only widely available drug for radical cure of Plasmodium vivax malaria. There is uncertainty whether the pharmacokinetic properties of primaquine are altered significantly in childhood or not. <br> <strong>Methods</strong> Glucose-6-phosphate dehydrogenase normal patients with uncomplicated P. vivax malaria were randomized to receive either chloroquine (25mg base/kg) or dihydroartemisinin-piperaquine (dihydroartemisinin 7mg/kg and piperaquine 55mg/kg) plus primaquine; given either as 0.5 mg base/kg/day for 14 days or 1 mg/kg/day for 7 days. Pre-dose day 7 venous plasma concentrations of chloroquine, desethylchloroquine, piperaquine, primaquine and carboxyprimaquine were measured. Methemoglobin levels were measured on day 7. <br> <strong>Results</strong> Day 7 primaquine and carboxyprimaquine concentrations were available for 641 patients. After adjustment for the primaquine mg/kg daily dose, day of sampling, partner drug, and fever clearance, there was a significant non-linear relationship between age and trough primaquine and carboxyprimaquine concentrations, and day methemoglobin levels. Compared to adults 30 years of age, children 5 years of age had trough primaquine concentrations 0.53 (95% CI: 0.39- 0.73) fold lower, trough carboxyprimaquine concentrations 0.45 (95% CI: 0.35- 0.55) fold lower, and day 7 methemoglobin levels 0.87 (95% CI: 0.58-1.27) fold lower. Increasing concentrations of piperaquine and chloroquine and poor metabolizer CYP 2D6 alleles were associated with higher day 7 primaquine and carboxyprimaquine concentrations. Higher blood methemoglobin concentrations were associated with a lower risk of recurrence. <br> <strong>Conclusion</strong> Young children have lower primaquine and carboxyprimaquine exposures, and lower levels of methemoglobinemia, than adults. Young children may need higher weight adjusted primaquine doses than adults. |
| spellingShingle | Chu, CS Watson, JA Phyo, AP Win, HH Yotyingaphiram, W Thinraow, S Soe, NL Aung, AA Wilaisrisak, P Kraft, K Imwong, M Hanpithakpong, W Blessborn, D Tarning, J Proux, S Ling, C Nosten, FH White, NJ Determinants of primaquine and carboxyprimaquine exposures in children and adults with Plasmodium vivax malaria |
| title | Determinants of primaquine and carboxyprimaquine exposures in children and adults with Plasmodium vivax malaria |
| title_full | Determinants of primaquine and carboxyprimaquine exposures in children and adults with Plasmodium vivax malaria |
| title_fullStr | Determinants of primaquine and carboxyprimaquine exposures in children and adults with Plasmodium vivax malaria |
| title_full_unstemmed | Determinants of primaquine and carboxyprimaquine exposures in children and adults with Plasmodium vivax malaria |
| title_short | Determinants of primaquine and carboxyprimaquine exposures in children and adults with Plasmodium vivax malaria |
| title_sort | determinants of primaquine and carboxyprimaquine exposures in children and adults with plasmodium vivax malaria |
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