Population pharmacokinetics of artesunate and dihydroartemisinin in pregnant and non-pregnant women with malaria
Abstract Background The World Health Organization endorses the use of artemisinin-based combination therapy for treatment of acute uncomplicated falciparum malaria in the second and third trimesters of pregnancy. However, the effects of pregnancy on the pharmacokinetics of artemisinin derivatives, s...
Published in: | Malaria Journal |
---|---|
Main Authors: | , , , , , , , , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
BMC
2011
|
Subjects: | |
Online Access: | https://doi.org/10.1186/1475-2875-10-114 https://doaj.org/article/3638ed3b54bf4497bec811838e644221 |
id |
ftdoajarticles:oai:doaj.org/article:3638ed3b54bf4497bec811838e644221 |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:3638ed3b54bf4497bec811838e644221 2023-05-15T15:18:08+02:00 Population pharmacokinetics of artesunate and dihydroartemisinin in pregnant and non-pregnant women with malaria Bose Carl Ryder Robert W Wesche David Hemingway-Foday Jennifer Douoguih Macaya Lokomba Vicky Atibu Joseph Koch Matthew A Capparelli Edmund Onyamboko Marie A Morris Carrie A Wright Linda Tshefu Antoinette K Meshnick Steven Fleckenstein Lawrence 2011-05-01T00:00:00Z https://doi.org/10.1186/1475-2875-10-114 https://doaj.org/article/3638ed3b54bf4497bec811838e644221 EN eng BMC http://www.malariajournal.com/content/10/1/114 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-10-114 1475-2875 https://doaj.org/article/3638ed3b54bf4497bec811838e644221 Malaria Journal, Vol 10, Iss 1, p 114 (2011) Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2011 ftdoajarticles https://doi.org/10.1186/1475-2875-10-114 2022-12-31T00:14:52Z Abstract Background The World Health Organization endorses the use of artemisinin-based combination therapy for treatment of acute uncomplicated falciparum malaria in the second and third trimesters of pregnancy. However, the effects of pregnancy on the pharmacokinetics of artemisinin derivatives, such as artesunate (AS), are poorly understood. In this analysis, the population pharmacokinetics of oral AS, and its active metabolite dihydroartemisinin (DHA), were studied in pregnant and non-pregnant women at the Kingasani Maternity Clinic in the DRC. Methods Data were obtained from 26 pregnant women in the second (22 - 26 weeks) or the third (32 - 36 weeks) trimester of pregnancy and from 25 non-pregnant female controls. All subjects received 200 mg AS. Plasma AS and DHA were measured using a validated LC-MS method. Estimates for pharmacokinetic and variability parameters were obtained through nonlinear mixed effects modelling. Results A simultaneous parent-metabolite model was developed consisting of mixed zero-order, lagged first-order absorption of AS, a one-compartment model for AS, and a one-compartment model for DHA. Complete conversion of AS to DHA was assumed. The model displayed satisfactory goodness-of-fit, stability, and predictive ability. Apparent clearance (CL/F) and volume of distribution (V/F) estimates, with 95% bootstrap confidence intervals, were as follows: 195 L (139-285 L) for AS V/F, 895 L/h (788-1045 L/h) for AS CL/F, 91.4 L (78.5-109 L) for DHA V/F, and 64.0 L/h (55.1-75.2 L/h) for DHA CL/F. The effect of pregnancy on DHA CL/F was determined to be significant, with a pregnancy-associated increase in DHA CL/F of 42.3% (19.7 - 72.3%). Conclusions In this analysis, pharmacokinetic modelling suggests that pregnant women have accelerated DHA clearance compared to non-pregnant women receiving orally administered AS. These findings, in conjunction with a previous non-compartmental analysis of the modelled data, provide further evidence that higher AS doses would be required to maintain similar ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 10 1 114 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Bose Carl Ryder Robert W Wesche David Hemingway-Foday Jennifer Douoguih Macaya Lokomba Vicky Atibu Joseph Koch Matthew A Capparelli Edmund Onyamboko Marie A Morris Carrie A Wright Linda Tshefu Antoinette K Meshnick Steven Fleckenstein Lawrence Population pharmacokinetics of artesunate and dihydroartemisinin in pregnant and non-pregnant women with malaria |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background The World Health Organization endorses the use of artemisinin-based combination therapy for treatment of acute uncomplicated falciparum malaria in the second and third trimesters of pregnancy. However, the effects of pregnancy on the pharmacokinetics of artemisinin derivatives, such as artesunate (AS), are poorly understood. In this analysis, the population pharmacokinetics of oral AS, and its active metabolite dihydroartemisinin (DHA), were studied in pregnant and non-pregnant women at the Kingasani Maternity Clinic in the DRC. Methods Data were obtained from 26 pregnant women in the second (22 - 26 weeks) or the third (32 - 36 weeks) trimester of pregnancy and from 25 non-pregnant female controls. All subjects received 200 mg AS. Plasma AS and DHA were measured using a validated LC-MS method. Estimates for pharmacokinetic and variability parameters were obtained through nonlinear mixed effects modelling. Results A simultaneous parent-metabolite model was developed consisting of mixed zero-order, lagged first-order absorption of AS, a one-compartment model for AS, and a one-compartment model for DHA. Complete conversion of AS to DHA was assumed. The model displayed satisfactory goodness-of-fit, stability, and predictive ability. Apparent clearance (CL/F) and volume of distribution (V/F) estimates, with 95% bootstrap confidence intervals, were as follows: 195 L (139-285 L) for AS V/F, 895 L/h (788-1045 L/h) for AS CL/F, 91.4 L (78.5-109 L) for DHA V/F, and 64.0 L/h (55.1-75.2 L/h) for DHA CL/F. The effect of pregnancy on DHA CL/F was determined to be significant, with a pregnancy-associated increase in DHA CL/F of 42.3% (19.7 - 72.3%). Conclusions In this analysis, pharmacokinetic modelling suggests that pregnant women have accelerated DHA clearance compared to non-pregnant women receiving orally administered AS. These findings, in conjunction with a previous non-compartmental analysis of the modelled data, provide further evidence that higher AS doses would be required to maintain similar ... |
format |
Article in Journal/Newspaper |
author |
Bose Carl Ryder Robert W Wesche David Hemingway-Foday Jennifer Douoguih Macaya Lokomba Vicky Atibu Joseph Koch Matthew A Capparelli Edmund Onyamboko Marie A Morris Carrie A Wright Linda Tshefu Antoinette K Meshnick Steven Fleckenstein Lawrence |
author_facet |
Bose Carl Ryder Robert W Wesche David Hemingway-Foday Jennifer Douoguih Macaya Lokomba Vicky Atibu Joseph Koch Matthew A Capparelli Edmund Onyamboko Marie A Morris Carrie A Wright Linda Tshefu Antoinette K Meshnick Steven Fleckenstein Lawrence |
author_sort |
Bose Carl |
title |
Population pharmacokinetics of artesunate and dihydroartemisinin in pregnant and non-pregnant women with malaria |
title_short |
Population pharmacokinetics of artesunate and dihydroartemisinin in pregnant and non-pregnant women with malaria |
title_full |
Population pharmacokinetics of artesunate and dihydroartemisinin in pregnant and non-pregnant women with malaria |
title_fullStr |
Population pharmacokinetics of artesunate and dihydroartemisinin in pregnant and non-pregnant women with malaria |
title_full_unstemmed |
Population pharmacokinetics of artesunate and dihydroartemisinin in pregnant and non-pregnant women with malaria |
title_sort |
population pharmacokinetics of artesunate and dihydroartemisinin in pregnant and non-pregnant women with malaria |
publisher |
BMC |
publishDate |
2011 |
url |
https://doi.org/10.1186/1475-2875-10-114 https://doaj.org/article/3638ed3b54bf4497bec811838e644221 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 10, Iss 1, p 114 (2011) |
op_relation |
http://www.malariajournal.com/content/10/1/114 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-10-114 1475-2875 https://doaj.org/article/3638ed3b54bf4497bec811838e644221 |
op_doi |
https://doi.org/10.1186/1475-2875-10-114 |
container_title |
Malaria Journal |
container_volume |
10 |
container_issue |
1 |
container_start_page |
114 |
_version_ |
1766348367554674688 |