Effect of pharmacogenetics on plasma lumefantrine pharmacokinetics and malaria treatment outcome in pregnant women
Abstract Background Pregnancy has considerable effects on the pharmacokinetic properties of drugs used to treat uncomplicated Plasmodium falciparum malaria. The role of pharmacogenetic variation on anti-malarial drug disposition and efficacy during pregnancy is not well investigated. The study aimed...
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ftdoajarticles:oai:doaj.org/article:6d52330c190f4dc681bbef9713f527c3 2023-05-15T15:14:26+02:00 Effect of pharmacogenetics on plasma lumefantrine pharmacokinetics and malaria treatment outcome in pregnant women Ritah F. Mutagonda Appolinary A. R. Kamuhabwa Omary M. S. Minzi Siriel N. Massawe Muhammad Asghar Manijeh V. Homann Anna Färnert Eleni Aklillu 2017-07-01T00:00:00Z https://doi.org/10.1186/s12936-017-1914-9 https://doaj.org/article/6d52330c190f4dc681bbef9713f527c3 EN eng BMC http://link.springer.com/article/10.1186/s12936-017-1914-9 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-017-1914-9 1475-2875 https://doaj.org/article/6d52330c190f4dc681bbef9713f527c3 Malaria Journal, Vol 16, Iss 1, Pp 1-10 (2017) Malaria in pregnancy Day 7 lumefantrine concentration Recrudescence Pharmacogenetics Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2017 ftdoajarticles https://doi.org/10.1186/s12936-017-1914-9 2022-12-31T02:05:30Z Abstract Background Pregnancy has considerable effects on the pharmacokinetic properties of drugs used to treat uncomplicated Plasmodium falciparum malaria. The role of pharmacogenetic variation on anti-malarial drug disposition and efficacy during pregnancy is not well investigated. The study aimed to examine the effect of pharmacogenetics on lumefantrine (LF) pharmacokinetics and treatment outcome in pregnant women. Methods Pregnant women with uncomplicated falciparum malaria were enrolled and treated with artemether-lumefantrine (ALu) at Mkuranga and Kisarawe district hospitals in Coast Region of Tanzania. Day-7 LF plasma concentration and genotyping forCYP2B6 (c.516G>T, c.983T>C), CYP3A4*1B, CYP3A5 (*3, *6, *7) and ABCB1 c.4036A4G were determined. Blood smear for parasite quantification by microscopy, and dried blood spot for parasite screening and genotyping using qPCR and nested PCR were collected at enrolment up to day 28 to differentiate between reinfection from recrudescence. Treatment response was recorded following the WHO protocol. Results In total, 92 pregnant women in their second and third trimester were included in the study and 424 samples were screened for presence of P. falciparum. Parasites were detected during the follow up period in 11 (12%) women between day 7 and 28 after treatment and PCR genotyping confirmed recrudescent infection in 7 (63.3%) women. The remaining four (36.4%) pregnant women had reinfection: one on day 14 and three on day 28. The overall PCR-corrected treatment failure rate was 9.0% (95% CI 4.4–17.4). Day 7 LF concentration was not significantly influenced by CYP2B6, CYP3A4*1B and ABCB1 c.4036A>G genotypes. Significant associations between CYP3A5 genotype and day 7 plasma LF concentrations was found, being higher in carriers of CYP3A5 defective variant alleles than CYP3A5*1/*1 genotype. No significant influence of CYP2B6, CYP3A5 and ABCB1 c.4036A>Genotypes on malaria treatment outcome were observed. However, CYP3A4*1B did affect malaria treatment outcome in ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 16 1 |
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Malaria in pregnancy Day 7 lumefantrine concentration Recrudescence Pharmacogenetics Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
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Malaria in pregnancy Day 7 lumefantrine concentration Recrudescence Pharmacogenetics Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Ritah F. Mutagonda Appolinary A. R. Kamuhabwa Omary M. S. Minzi Siriel N. Massawe Muhammad Asghar Manijeh V. Homann Anna Färnert Eleni Aklillu Effect of pharmacogenetics on plasma lumefantrine pharmacokinetics and malaria treatment outcome in pregnant women |
topic_facet |
Malaria in pregnancy Day 7 lumefantrine concentration Recrudescence Pharmacogenetics Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Pregnancy has considerable effects on the pharmacokinetic properties of drugs used to treat uncomplicated Plasmodium falciparum malaria. The role of pharmacogenetic variation on anti-malarial drug disposition and efficacy during pregnancy is not well investigated. The study aimed to examine the effect of pharmacogenetics on lumefantrine (LF) pharmacokinetics and treatment outcome in pregnant women. Methods Pregnant women with uncomplicated falciparum malaria were enrolled and treated with artemether-lumefantrine (ALu) at Mkuranga and Kisarawe district hospitals in Coast Region of Tanzania. Day-7 LF plasma concentration and genotyping forCYP2B6 (c.516G>T, c.983T>C), CYP3A4*1B, CYP3A5 (*3, *6, *7) and ABCB1 c.4036A4G were determined. Blood smear for parasite quantification by microscopy, and dried blood spot for parasite screening and genotyping using qPCR and nested PCR were collected at enrolment up to day 28 to differentiate between reinfection from recrudescence. Treatment response was recorded following the WHO protocol. Results In total, 92 pregnant women in their second and third trimester were included in the study and 424 samples were screened for presence of P. falciparum. Parasites were detected during the follow up period in 11 (12%) women between day 7 and 28 after treatment and PCR genotyping confirmed recrudescent infection in 7 (63.3%) women. The remaining four (36.4%) pregnant women had reinfection: one on day 14 and three on day 28. The overall PCR-corrected treatment failure rate was 9.0% (95% CI 4.4–17.4). Day 7 LF concentration was not significantly influenced by CYP2B6, CYP3A4*1B and ABCB1 c.4036A>G genotypes. Significant associations between CYP3A5 genotype and day 7 plasma LF concentrations was found, being higher in carriers of CYP3A5 defective variant alleles than CYP3A5*1/*1 genotype. No significant influence of CYP2B6, CYP3A5 and ABCB1 c.4036A>Genotypes on malaria treatment outcome were observed. However, CYP3A4*1B did affect malaria treatment outcome in ... |
format |
Article in Journal/Newspaper |
author |
Ritah F. Mutagonda Appolinary A. R. Kamuhabwa Omary M. S. Minzi Siriel N. Massawe Muhammad Asghar Manijeh V. Homann Anna Färnert Eleni Aklillu |
author_facet |
Ritah F. Mutagonda Appolinary A. R. Kamuhabwa Omary M. S. Minzi Siriel N. Massawe Muhammad Asghar Manijeh V. Homann Anna Färnert Eleni Aklillu |
author_sort |
Ritah F. Mutagonda |
title |
Effect of pharmacogenetics on plasma lumefantrine pharmacokinetics and malaria treatment outcome in pregnant women |
title_short |
Effect of pharmacogenetics on plasma lumefantrine pharmacokinetics and malaria treatment outcome in pregnant women |
title_full |
Effect of pharmacogenetics on plasma lumefantrine pharmacokinetics and malaria treatment outcome in pregnant women |
title_fullStr |
Effect of pharmacogenetics on plasma lumefantrine pharmacokinetics and malaria treatment outcome in pregnant women |
title_full_unstemmed |
Effect of pharmacogenetics on plasma lumefantrine pharmacokinetics and malaria treatment outcome in pregnant women |
title_sort |
effect of pharmacogenetics on plasma lumefantrine pharmacokinetics and malaria treatment outcome in pregnant women |
publisher |
BMC |
publishDate |
2017 |
url |
https://doi.org/10.1186/s12936-017-1914-9 https://doaj.org/article/6d52330c190f4dc681bbef9713f527c3 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 16, Iss 1, Pp 1-10 (2017) |
op_relation |
http://link.springer.com/article/10.1186/s12936-017-1914-9 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-017-1914-9 1475-2875 https://doaj.org/article/6d52330c190f4dc681bbef9713f527c3 |
op_doi |
https://doi.org/10.1186/s12936-017-1914-9 |
container_title |
Malaria Journal |
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16 |
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1766344886055862272 |