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Artesunate/dihydroartemisinin pharmacokinetics in acute falciparum malaria in pregnancy: absorption, bioavailability, disposition and disease effects
AIM: To determine if reported lower plasma concentrations of artemisinin derivatives for malaria in pregnancy result from reduced oral bioavailability, expanded volume of distribution or increased clearance. METHODS: In a sequentially assigned crossover treatment study, pregnant women with uncomplic...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Science Inc
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3370352/ https://www.ncbi.nlm.nih.gov/pubmed/21950338 http://dx.doi.org/10.1111/j.1365-2125.2011.04103.x |
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author | McGready, Rose Phyo, Aung Pyae Rijken, Marcus J Tarning, Joel Lindegardh, Niklas Hanpithakpon, Warunee Than, Hla Hla Hlaing, Nathar Zin, Naw Thida Singhasivanon, Pratap White, Nicholas J Nosten, François |
author_facet | McGready, Rose Phyo, Aung Pyae Rijken, Marcus J Tarning, Joel Lindegardh, Niklas Hanpithakpon, Warunee Than, Hla Hla Hlaing, Nathar Zin, Naw Thida Singhasivanon, Pratap White, Nicholas J Nosten, François |
author_sort | McGready, Rose |
collection | PubMed |
description | AIM: To determine if reported lower plasma concentrations of artemisinin derivatives for malaria in pregnancy result from reduced oral bioavailability, expanded volume of distribution or increased clearance. METHODS: In a sequentially assigned crossover treatment study, pregnant women with uncomplicated falciparum malaria received i.v. artesunate (i.v. ARS) (4 mg kg(−1)) on the first day and oral ARS (4 mg kg(−1)) on the second, or, oral on the first and i.v. on the second, in both groups followed by oral ARS (4 mg kg(−1) day(−1)) for 5 days. Plasma concentrations of ARS and dihyroartemisinin (DHA) were measured by liquid chromatography-mass-spectrometry on days 0, 1, 2 and 6. Controls were the same women restudied when healthy (3 months post partum). RESULTS: I.v. ARS administration resulted in similar ARS and DHA pharmacokinetics in pregnant women with malaria (n = 20) and in controls (n = 14). Oral administration resulted in higher total drug exposure in pregnancy [AUC (95% CI) in (ng ml(−1) h)/(mg kg(−1))] of 55.1 (30.1, 100.0) vs. 26.5 (12.2, 54.3) for ARS, P = 0.002 and 673 (386, 1130) vs. 523 (351, 724) for DHA, P = 0.007. The corresponding median absolute oral bioavailability (F%) was 21.7 (12.6, 75.1) vs. 9.9 (6.0, 36.81) for ARS (P = 0.046) and 77.0 (42.2, 129) vs. 72.7 (42.0, 87.7) for DHA, P = 0.033. Total DHA exposure was lower at day 6 in pregnant women with malaria (P < 0.001) compared with day 0 or 1, but not in the controls (P = 0.084). CONCLUSIONS: This study demonstrates the effects of malaria on oral ARS drug disposition are greater than those of pregnancy. This probably results from a disease related reduction in first pass metabolism. The data are reassuring regarding current dosing recommendations. |
format | Online Article Text |
id | pubmed-3370352 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Blackwell Science Inc |
record_format | MEDLINE/PubMed |
spelling | pubmed-33703522012-06-20 Artesunate/dihydroartemisinin pharmacokinetics in acute falciparum malaria in pregnancy: absorption, bioavailability, disposition and disease effects McGready, Rose Phyo, Aung Pyae Rijken, Marcus J Tarning, Joel Lindegardh, Niklas Hanpithakpon, Warunee Than, Hla Hla Hlaing, Nathar Zin, Naw Thida Singhasivanon, Pratap White, Nicholas J Nosten, François Br J Clin Pharmacol Drugs in Pregnancy and Lactation AIM: To determine if reported lower plasma concentrations of artemisinin derivatives for malaria in pregnancy result from reduced oral bioavailability, expanded volume of distribution or increased clearance. METHODS: In a sequentially assigned crossover treatment study, pregnant women with uncomplicated falciparum malaria received i.v. artesunate (i.v. ARS) (4 mg kg(−1)) on the first day and oral ARS (4 mg kg(−1)) on the second, or, oral on the first and i.v. on the second, in both groups followed by oral ARS (4 mg kg(−1) day(−1)) for 5 days. Plasma concentrations of ARS and dihyroartemisinin (DHA) were measured by liquid chromatography-mass-spectrometry on days 0, 1, 2 and 6. Controls were the same women restudied when healthy (3 months post partum). RESULTS: I.v. ARS administration resulted in similar ARS and DHA pharmacokinetics in pregnant women with malaria (n = 20) and in controls (n = 14). Oral administration resulted in higher total drug exposure in pregnancy [AUC (95% CI) in (ng ml(−1) h)/(mg kg(−1))] of 55.1 (30.1, 100.0) vs. 26.5 (12.2, 54.3) for ARS, P = 0.002 and 673 (386, 1130) vs. 523 (351, 724) for DHA, P = 0.007. The corresponding median absolute oral bioavailability (F%) was 21.7 (12.6, 75.1) vs. 9.9 (6.0, 36.81) for ARS (P = 0.046) and 77.0 (42.2, 129) vs. 72.7 (42.0, 87.7) for DHA, P = 0.033. Total DHA exposure was lower at day 6 in pregnant women with malaria (P < 0.001) compared with day 0 or 1, but not in the controls (P = 0.084). CONCLUSIONS: This study demonstrates the effects of malaria on oral ARS drug disposition are greater than those of pregnancy. This probably results from a disease related reduction in first pass metabolism. The data are reassuring regarding current dosing recommendations. Blackwell Science Inc 2012-03 2011-09-28 /pmc/articles/PMC3370352/ /pubmed/21950338 http://dx.doi.org/10.1111/j.1365-2125.2011.04103.x Text en © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society |
spellingShingle | Drugs in Pregnancy and Lactation McGready, Rose Phyo, Aung Pyae Rijken, Marcus J Tarning, Joel Lindegardh, Niklas Hanpithakpon, Warunee Than, Hla Hla Hlaing, Nathar Zin, Naw Thida Singhasivanon, Pratap White, Nicholas J Nosten, François Artesunate/dihydroartemisinin pharmacokinetics in acute falciparum malaria in pregnancy: absorption, bioavailability, disposition and disease effects |
title | Artesunate/dihydroartemisinin pharmacokinetics in acute falciparum malaria in pregnancy: absorption, bioavailability, disposition and disease effects |
title_full | Artesunate/dihydroartemisinin pharmacokinetics in acute falciparum malaria in pregnancy: absorption, bioavailability, disposition and disease effects |
title_fullStr | Artesunate/dihydroartemisinin pharmacokinetics in acute falciparum malaria in pregnancy: absorption, bioavailability, disposition and disease effects |
title_full_unstemmed | Artesunate/dihydroartemisinin pharmacokinetics in acute falciparum malaria in pregnancy: absorption, bioavailability, disposition and disease effects |
title_short | Artesunate/dihydroartemisinin pharmacokinetics in acute falciparum malaria in pregnancy: absorption, bioavailability, disposition and disease effects |
title_sort | artesunate/dihydroartemisinin pharmacokinetics in acute falciparum malaria in pregnancy: absorption, bioavailability, disposition and disease effects |
topic | Drugs in Pregnancy and Lactation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3370352/ https://www.ncbi.nlm.nih.gov/pubmed/21950338 http://dx.doi.org/10.1111/j.1365-2125.2011.04103.x |
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