Persistence of atovaquone in human sera following treatment: inhibition of Plasmodium falciparum development in vivo and in vitro.
Published pharmacokinetic data indicate that after treatment of patients with therapeutic doses of atovaquone/proguanil hydrochloride (Malarone, GlaxoSmithKline Research Triangle Park, NC), the plasma half-lives of these drugs are 70h and 15h, respectively. However, using two biologic assays (mosqui...
| Main Authors: | , |
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| Format: | Journal article |
| Language: | English |
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2003
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| _version_ | 1797054102689021952 |
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| author | Butcher, G Sinden, R |
| author_facet | Butcher, G Sinden, R |
| author_sort | Butcher, G |
| collection | OXFORD |
| description | Published pharmacokinetic data indicate that after treatment of patients with therapeutic doses of atovaquone/proguanil hydrochloride (Malarone, GlaxoSmithKline Research Triangle Park, NC), the plasma half-lives of these drugs are 70h and 15h, respectively. However, using two biologic assays (mosquito transmission and in vitro asexual stage development), we demonstrate here that sera from volunteers treated with atovaquone/proguanil retained activity against Plasmodium falciparum up to 6 weeks after such treatment. This activity was due to atovaquone, as administration of this drug alone replicated the data obtained with the combination. Most notably, asexual stage development of an atovaquone-resistant strain (NGATV01) of P. falciparum was not inhibited by sera taken after atovaquone treatment. These data indicate that for atovaquone, biologic assays, though not quantitative, are more sensitive than the usual physicochemical assays. Also, persistence of atovaquone in plasma at low concentrations for long periods may increase the risk of resistant parasites arising. |
| first_indexed | 2024-03-06T18:52:51Z |
| format | Journal article |
| id | oxford-uuid:10d73a7f-b4cc-4ae2-9fbb-40d9a92e4418 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:52:51Z |
| publishDate | 2003 |
| record_format | dspace |
| spelling | oxford-uuid:10d73a7f-b4cc-4ae2-9fbb-40d9a92e44182022-03-26T09:58:40ZPersistence of atovaquone in human sera following treatment: inhibition of Plasmodium falciparum development in vivo and in vitro.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:10d73a7f-b4cc-4ae2-9fbb-40d9a92e4418EnglishSymplectic Elements at Oxford2003Butcher, GSinden, RPublished pharmacokinetic data indicate that after treatment of patients with therapeutic doses of atovaquone/proguanil hydrochloride (Malarone, GlaxoSmithKline Research Triangle Park, NC), the plasma half-lives of these drugs are 70h and 15h, respectively. However, using two biologic assays (mosquito transmission and in vitro asexual stage development), we demonstrate here that sera from volunteers treated with atovaquone/proguanil retained activity against Plasmodium falciparum up to 6 weeks after such treatment. This activity was due to atovaquone, as administration of this drug alone replicated the data obtained with the combination. Most notably, asexual stage development of an atovaquone-resistant strain (NGATV01) of P. falciparum was not inhibited by sera taken after atovaquone treatment. These data indicate that for atovaquone, biologic assays, though not quantitative, are more sensitive than the usual physicochemical assays. Also, persistence of atovaquone in plasma at low concentrations for long periods may increase the risk of resistant parasites arising. |
| spellingShingle | Butcher, G Sinden, R Persistence of atovaquone in human sera following treatment: inhibition of Plasmodium falciparum development in vivo and in vitro. |
| title | Persistence of atovaquone in human sera following treatment: inhibition of Plasmodium falciparum development in vivo and in vitro. |
| title_full | Persistence of atovaquone in human sera following treatment: inhibition of Plasmodium falciparum development in vivo and in vitro. |
| title_fullStr | Persistence of atovaquone in human sera following treatment: inhibition of Plasmodium falciparum development in vivo and in vitro. |
| title_full_unstemmed | Persistence of atovaquone in human sera following treatment: inhibition of Plasmodium falciparum development in vivo and in vitro. |
| title_short | Persistence of atovaquone in human sera following treatment: inhibition of Plasmodium falciparum development in vivo and in vitro. |
| title_sort | persistence of atovaquone in human sera following treatment inhibition of plasmodium falciparum development in vivo and in vitro |
| work_keys_str_mv | AT butcherg persistenceofatovaquoneinhumanserafollowingtreatmentinhibitionofplasmodiumfalciparumdevelopmentinvivoandinvitro AT sindenr persistenceofatovaquoneinhumanserafollowingtreatmentinhibitionofplasmodiumfalciparumdevelopmentinvivoandinvitro |