Pharmacokinetics of co-formulated mefloquine and artesunate in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum infection in Burkina Faso
Mefloquine/artesunate has recently been developed as a fixed-dose combination, providing a promising rescue/alternative treatment for malaria during pregnancy. However, limited data are available on the effect of pregnancy on its pharmacokinetic properties. This study was conducted to assess the pha...
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| Veröffentlicht in: | Journal of antimicrobial chemotherapy 2014-09, Vol.69 (9), p.2499-2507 |
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| creator | Valea, Innocent Tinto, Halidou Traore-Coulibaly, Maminata Toe, Laeticia C Lindegardh, Niklas Tarning, Joel Van Geertruyden, Jean-Pierre D'Alessandro, Umberto Davies, Geraint R Ward, Stephen A |
| description | Mefloquine/artesunate has recently been developed as a fixed-dose combination, providing a promising rescue/alternative treatment for malaria during pregnancy. However, limited data are available on the effect of pregnancy on its pharmacokinetic properties. This study was conducted to assess the pharmacokinetic properties of mefloquine/carboxymefloquine and artesunate/dihydroartemisinin in pregnant and non-pregnant women with uncomplicated malaria.
Twenty-four women in their second and third trimesters of pregnancy and 24 paired non-pregnant women were enrolled. All patients were treated for uncomplicated Plasmodium falciparum malaria with a standard fixed-dose combination of oral mefloquine and artesunate one daily over 3 days. Frequent blood samples were collected before treatment and at scheduled times post-dose for the drug measurements and pharmacokinetic analyses. The study was registered at www.clinicaltrials.gov (identifier: NCT00701961).
The total median exposure to mefloquine and dihydroartemisinin was not significantly different between the pregnant and non-pregnant women (P>0.05). There was a trend of higher exposure to mefloquine in the pregnant women, but this difference did not reach statistical significance (656700 versus 542400 h × ng/mL; P=0.059). However, the total exposure to carboxymefloquine was 49% lower during pregnancy (735600 versus 1499000 h × ng/mL; P |
| doi_str_mv | 10.1093/jac/dku154 |
| format | Article |
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Twenty-four women in their second and third trimesters of pregnancy and 24 paired non-pregnant women were enrolled. All patients were treated for uncomplicated Plasmodium falciparum malaria with a standard fixed-dose combination of oral mefloquine and artesunate one daily over 3 days. Frequent blood samples were collected before treatment and at scheduled times post-dose for the drug measurements and pharmacokinetic analyses. The study was registered at www.clinicaltrials.gov (identifier: NCT00701961).
The total median exposure to mefloquine and dihydroartemisinin was not significantly different between the pregnant and non-pregnant women (P>0.05). There was a trend of higher exposure to mefloquine in the pregnant women, but this difference did not reach statistical significance (656700 versus 542400 h × ng/mL; P=0.059). However, the total exposure to carboxymefloquine was 49% lower during pregnancy (735600 versus 1499000 h × ng/mL; P<0.001) and the total drug exposure to artesunate was 42% higher during pregnancy (89.0 versus 62.9 h × ng/mL; P=0.039) compared with non-pregnant controls.
The plasma levels of mefloquine and dihydroartemisinin appeared to be similar in both pregnant and non-pregnant women, but there were significant differences in carboxymefloquine and artesunate exposure. The data presented here do not warrant a dose adjustment in pregnant patients, but an extensive analysis of the data could provide a better understanding of these findings.</description><identifier>ISSN: 0305-7453</identifier><identifier>EISSN: 1460-2091</identifier><identifier>DOI: 10.1093/jac/dku154</identifier><identifier>PMID: 24891429</identifier><language>eng</language><publisher>England: Oxford Publishing Limited (England)</publisher><subject>Adolescent ; Adult ; Antimalarials - administration & dosage ; Antimalarials - pharmacokinetics ; Artemisinins - administration & dosage ; Artemisinins - pharmacokinetics ; Burkina Faso ; Drug Combinations ; Female ; Humans ; Kinetics ; Malaria, Falciparum - drug therapy ; Mefloquine - administration & dosage ; Mefloquine - pharmacokinetics ; Original Research ; Parasites ; Pharmacology ; Plasma - chemistry ; Pregnancy ; Pregnancy Complications, Infectious - drug therapy ; Prescription drugs ; Women ; Young Adult</subject><ispartof>Journal of antimicrobial chemotherapy, 2014-09, Vol.69 (9), p.2499-2507</ispartof><rights>The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.</rights><rights>Copyright Oxford Publishing Limited(England) Sep 2014</rights><rights>The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c406t-be733233aa06fb2c7c0044439b42b9f55427cecd7162dd21a5e1987a361efe313</citedby><cites>FETCH-LOGICAL-c406t-be733233aa06fb2c7c0044439b42b9f55427cecd7162dd21a5e1987a361efe313</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24891429$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Valea, Innocent</creatorcontrib><creatorcontrib>Tinto, Halidou</creatorcontrib><creatorcontrib>Traore-Coulibaly, Maminata</creatorcontrib><creatorcontrib>Toe, Laeticia C</creatorcontrib><creatorcontrib>Lindegardh, Niklas</creatorcontrib><creatorcontrib>Tarning, Joel</creatorcontrib><creatorcontrib>Van Geertruyden, Jean-Pierre</creatorcontrib><creatorcontrib>D'Alessandro, Umberto</creatorcontrib><creatorcontrib>Davies, Geraint R</creatorcontrib><creatorcontrib>Ward, Stephen A</creatorcontrib><title>Pharmacokinetics of co-formulated mefloquine and artesunate in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum infection in Burkina Faso</title><title>Journal of antimicrobial chemotherapy</title><addtitle>J Antimicrob Chemother</addtitle><description>Mefloquine/artesunate has recently been developed as a fixed-dose combination, providing a promising rescue/alternative treatment for malaria during pregnancy. However, limited data are available on the effect of pregnancy on its pharmacokinetic properties. This study was conducted to assess the pharmacokinetic properties of mefloquine/carboxymefloquine and artesunate/dihydroartemisinin in pregnant and non-pregnant women with uncomplicated malaria.
Twenty-four women in their second and third trimesters of pregnancy and 24 paired non-pregnant women were enrolled. All patients were treated for uncomplicated Plasmodium falciparum malaria with a standard fixed-dose combination of oral mefloquine and artesunate one daily over 3 days. Frequent blood samples were collected before treatment and at scheduled times post-dose for the drug measurements and pharmacokinetic analyses. The study was registered at www.clinicaltrials.gov (identifier: NCT00701961).
The total median exposure to mefloquine and dihydroartemisinin was not significantly different between the pregnant and non-pregnant women (P>0.05). There was a trend of higher exposure to mefloquine in the pregnant women, but this difference did not reach statistical significance (656700 versus 542400 h × ng/mL; P=0.059). However, the total exposure to carboxymefloquine was 49% lower during pregnancy (735600 versus 1499000 h × ng/mL; P<0.001) and the total drug exposure to artesunate was 42% higher during pregnancy (89.0 versus 62.9 h × ng/mL; P=0.039) compared with non-pregnant controls.
The plasma levels of mefloquine and dihydroartemisinin appeared to be similar in both pregnant and non-pregnant women, but there were significant differences in carboxymefloquine and artesunate exposure. The data presented here do not warrant a dose adjustment in pregnant patients, but an extensive analysis of the data could provide a better understanding of these findings.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Antimalarials - administration & dosage</subject><subject>Antimalarials - pharmacokinetics</subject><subject>Artemisinins - administration & dosage</subject><subject>Artemisinins - pharmacokinetics</subject><subject>Burkina Faso</subject><subject>Drug Combinations</subject><subject>Female</subject><subject>Humans</subject><subject>Kinetics</subject><subject>Malaria, Falciparum - drug therapy</subject><subject>Mefloquine - administration & dosage</subject><subject>Mefloquine - pharmacokinetics</subject><subject>Original Research</subject><subject>Parasites</subject><subject>Pharmacology</subject><subject>Plasma - chemistry</subject><subject>Pregnancy</subject><subject>Pregnancy Complications, Infectious - drug therapy</subject><subject>Prescription drugs</subject><subject>Women</subject><subject>Young Adult</subject><issn>0305-7453</issn><issn>1460-2091</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkc1u1DAUhS0EotPCpg-ALLFDCvVfksmmUqloi1SJLmBt3Th2x9PYDv6h4nF407qddgSra93z6dwjH4SOKflMycBPtqBOprtCW_EKrajoSMPIQF-jFeGkbXrR8gN0mNKWENK13fotOmBiPVDBhhX6e7OB6ECFO-t1tirhYLAKjQnRlRmynrDTZg6_StUx-AlDzDoVXyVsPV6ivvXg85Pkg2_2i_vgtMf3Nm9w8Sq4Zbbqye9mhuTCZIvDBmZlF4j1ab3RKtvgH12_lFjzAL6AFN6hNxVL-v3zPEI_L77-OL9qrr9ffjs_u26UIF1uRt1zzjgHIJ0ZmeoVIUIIPoyCjYNpW8F6pdXU045NE6PQajqse-Ad1UZzyo_Q6c53KaPTk9I-R5jlEq2D-EcGsPJ_xduNvA2_paCc8DWrBh-fDWL9Lp2y3IYSfc0saT3fip7TrlKfdpSKIaWozf4CJfKxTlnrlLs6K_zh30x79KU__gD5HqGD</recordid><startdate>20140901</startdate><enddate>20140901</enddate><creator>Valea, Innocent</creator><creator>Tinto, Halidou</creator><creator>Traore-Coulibaly, Maminata</creator><creator>Toe, Laeticia C</creator><creator>Lindegardh, Niklas</creator><creator>Tarning, Joel</creator><creator>Van Geertruyden, Jean-Pierre</creator><creator>D'Alessandro, Umberto</creator><creator>Davies, Geraint R</creator><creator>Ward, Stephen A</creator><general>Oxford Publishing Limited (England)</general><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QO</scope><scope>7T7</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>NAPCQ</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>20140901</creationdate><title>Pharmacokinetics of co-formulated mefloquine and artesunate in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum infection in Burkina Faso</title><author>Valea, Innocent ; Tinto, Halidou ; Traore-Coulibaly, Maminata ; Toe, Laeticia C ; Lindegardh, Niklas ; Tarning, Joel ; Van Geertruyden, Jean-Pierre ; D'Alessandro, Umberto ; Davies, Geraint R ; Ward, Stephen A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c406t-be733233aa06fb2c7c0044439b42b9f55427cecd7162dd21a5e1987a361efe313</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Antimalarials - administration & dosage</topic><topic>Antimalarials - pharmacokinetics</topic><topic>Artemisinins - administration & dosage</topic><topic>Artemisinins - pharmacokinetics</topic><topic>Burkina Faso</topic><topic>Drug Combinations</topic><topic>Female</topic><topic>Humans</topic><topic>Kinetics</topic><topic>Malaria, Falciparum - drug therapy</topic><topic>Mefloquine - administration & dosage</topic><topic>Mefloquine - pharmacokinetics</topic><topic>Original Research</topic><topic>Parasites</topic><topic>Pharmacology</topic><topic>Plasma - chemistry</topic><topic>Pregnancy</topic><topic>Pregnancy Complications, Infectious - drug therapy</topic><topic>Prescription drugs</topic><topic>Women</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Valea, Innocent</creatorcontrib><creatorcontrib>Tinto, Halidou</creatorcontrib><creatorcontrib>Traore-Coulibaly, Maminata</creatorcontrib><creatorcontrib>Toe, Laeticia C</creatorcontrib><creatorcontrib>Lindegardh, Niklas</creatorcontrib><creatorcontrib>Tarning, Joel</creatorcontrib><creatorcontrib>Van Geertruyden, Jean-Pierre</creatorcontrib><creatorcontrib>D'Alessandro, Umberto</creatorcontrib><creatorcontrib>Davies, Geraint R</creatorcontrib><creatorcontrib>Ward, Stephen A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of antimicrobial chemotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Valea, Innocent</au><au>Tinto, Halidou</au><au>Traore-Coulibaly, Maminata</au><au>Toe, Laeticia C</au><au>Lindegardh, Niklas</au><au>Tarning, Joel</au><au>Van Geertruyden, Jean-Pierre</au><au>D'Alessandro, Umberto</au><au>Davies, Geraint R</au><au>Ward, Stephen A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacokinetics of co-formulated mefloquine and artesunate in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum infection in Burkina Faso</atitle><jtitle>Journal of antimicrobial chemotherapy</jtitle><addtitle>J Antimicrob Chemother</addtitle><date>2014-09-01</date><risdate>2014</risdate><volume>69</volume><issue>9</issue><spage>2499</spage><epage>2507</epage><pages>2499-2507</pages><issn>0305-7453</issn><eissn>1460-2091</eissn><abstract>Mefloquine/artesunate has recently been developed as a fixed-dose combination, providing a promising rescue/alternative treatment for malaria during pregnancy. However, limited data are available on the effect of pregnancy on its pharmacokinetic properties. This study was conducted to assess the pharmacokinetic properties of mefloquine/carboxymefloquine and artesunate/dihydroartemisinin in pregnant and non-pregnant women with uncomplicated malaria.
Twenty-four women in their second and third trimesters of pregnancy and 24 paired non-pregnant women were enrolled. All patients were treated for uncomplicated Plasmodium falciparum malaria with a standard fixed-dose combination of oral mefloquine and artesunate one daily over 3 days. Frequent blood samples were collected before treatment and at scheduled times post-dose for the drug measurements and pharmacokinetic analyses. The study was registered at www.clinicaltrials.gov (identifier: NCT00701961).
The total median exposure to mefloquine and dihydroartemisinin was not significantly different between the pregnant and non-pregnant women (P>0.05). There was a trend of higher exposure to mefloquine in the pregnant women, but this difference did not reach statistical significance (656700 versus 542400 h × ng/mL; P=0.059). However, the total exposure to carboxymefloquine was 49% lower during pregnancy (735600 versus 1499000 h × ng/mL; P<0.001) and the total drug exposure to artesunate was 42% higher during pregnancy (89.0 versus 62.9 h × ng/mL; P=0.039) compared with non-pregnant controls.
The plasma levels of mefloquine and dihydroartemisinin appeared to be similar in both pregnant and non-pregnant women, but there were significant differences in carboxymefloquine and artesunate exposure. The data presented here do not warrant a dose adjustment in pregnant patients, but an extensive analysis of the data could provide a better understanding of these findings.</abstract><cop>England</cop><pub>Oxford Publishing Limited (England)</pub><pmid>24891429</pmid><doi>10.1093/jac/dku154</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Adult Antimalarials - administration & dosage Antimalarials - pharmacokinetics Artemisinins - administration & dosage Artemisinins - pharmacokinetics Burkina Faso Drug Combinations Female Humans Kinetics Malaria, Falciparum - drug therapy Mefloquine - administration & dosage Mefloquine - pharmacokinetics Original Research Parasites Pharmacology Plasma - chemistry Pregnancy Pregnancy Complications, Infectious - drug therapy Prescription drugs Women Young Adult |
| title | Pharmacokinetics of co-formulated mefloquine and artesunate in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum infection in Burkina Faso |
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