The pharmacokinetics of atovaquone and proguanil in pregnant women with acute falciparum malaria.
OBJECTIVE: To determine the pharmacokinetic properties of atovaquone, proguanil, and the triazine metabolite cycloguanil in women with recrudescent multi-drug resistant falciparum malaria during the second and third trimesters of pregnancy treated by artesunate-atovaquone-proguanil. METHODS: Serial...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2003
|
| _version_ | 1797078439526662144 |
|---|---|
| author | Mcgready, R Stepniewska, K Edstein, MD Cho, T Gilveray, G Looareesuwan, S White, N Nosten, F |
| author_facet | Mcgready, R Stepniewska, K Edstein, MD Cho, T Gilveray, G Looareesuwan, S White, N Nosten, F |
| author_sort | Mcgready, R |
| collection | OXFORD |
| description | OBJECTIVE: To determine the pharmacokinetic properties of atovaquone, proguanil, and the triazine metabolite cycloguanil in women with recrudescent multi-drug resistant falciparum malaria during the second and third trimesters of pregnancy treated by artesunate-atovaquone-proguanil. METHODS: Serial plasma concentrations of atovaquone, proguanil and cycloguanil were measured in 24 women at baseline and after the final dose of the 3-day treatment with atovaquone (20 mg/kg/day) plus proguanil (8 mg/kg/day) plus artesunate (4 mg/kg/day) daily. RESULTS: The triple combination was well tolerated and highly effective. The outcomes of pregnancy were all normal. Population mean (+/- SEM) oral clearance (Cl/F) estimates were 313+/-33 ml/h/kg and 1109+/-43 ml/h/kg, total apparent volume of distribution (Vd/F) 13.0+/-1.3 l/kg and 22.9+/-1.4 l/kg, and terminal elimination half-life; 29.1 h and 14.3 h, for atovaquone and proguanil, respectively. Using conventional and population pharmacokinetic analyses, Cl/F and Vd/F estimates for both drugs were approximately twice, and plasma concentrations less than half those reported previously in healthy subjects and patients with acute malaria. CONCLUSION: Artesunate-atovaquone-proguanil is a promising treatment for multi-drug resistant falciparum malaria during pregnancy, but the dose of atovaquone-proguanil may need to be increased. |
| first_indexed | 2024-03-07T00:31:50Z |
| format | Journal article |
| id | oxford-uuid:8012cc89-d065-4979-8c1e-5c09c5997c87 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:31:50Z |
| publishDate | 2003 |
| record_format | dspace |
| spelling | oxford-uuid:8012cc89-d065-4979-8c1e-5c09c5997c872022-03-26T21:21:05ZThe pharmacokinetics of atovaquone and proguanil in pregnant women with acute falciparum malaria.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8012cc89-d065-4979-8c1e-5c09c5997c87EnglishSymplectic Elements at Oxford2003Mcgready, RStepniewska, KEdstein, MDCho, TGilveray, GLooareesuwan, SWhite, NNosten, F OBJECTIVE: To determine the pharmacokinetic properties of atovaquone, proguanil, and the triazine metabolite cycloguanil in women with recrudescent multi-drug resistant falciparum malaria during the second and third trimesters of pregnancy treated by artesunate-atovaquone-proguanil. METHODS: Serial plasma concentrations of atovaquone, proguanil and cycloguanil were measured in 24 women at baseline and after the final dose of the 3-day treatment with atovaquone (20 mg/kg/day) plus proguanil (8 mg/kg/day) plus artesunate (4 mg/kg/day) daily. RESULTS: The triple combination was well tolerated and highly effective. The outcomes of pregnancy were all normal. Population mean (+/- SEM) oral clearance (Cl/F) estimates were 313+/-33 ml/h/kg and 1109+/-43 ml/h/kg, total apparent volume of distribution (Vd/F) 13.0+/-1.3 l/kg and 22.9+/-1.4 l/kg, and terminal elimination half-life; 29.1 h and 14.3 h, for atovaquone and proguanil, respectively. Using conventional and population pharmacokinetic analyses, Cl/F and Vd/F estimates for both drugs were approximately twice, and plasma concentrations less than half those reported previously in healthy subjects and patients with acute malaria. CONCLUSION: Artesunate-atovaquone-proguanil is a promising treatment for multi-drug resistant falciparum malaria during pregnancy, but the dose of atovaquone-proguanil may need to be increased. |
| spellingShingle | Mcgready, R Stepniewska, K Edstein, MD Cho, T Gilveray, G Looareesuwan, S White, N Nosten, F The pharmacokinetics of atovaquone and proguanil in pregnant women with acute falciparum malaria. |
| title | The pharmacokinetics of atovaquone and proguanil in pregnant women with acute falciparum malaria. |
| title_full | The pharmacokinetics of atovaquone and proguanil in pregnant women with acute falciparum malaria. |
| title_fullStr | The pharmacokinetics of atovaquone and proguanil in pregnant women with acute falciparum malaria. |
| title_full_unstemmed | The pharmacokinetics of atovaquone and proguanil in pregnant women with acute falciparum malaria. |
| title_short | The pharmacokinetics of atovaquone and proguanil in pregnant women with acute falciparum malaria. |
| title_sort | pharmacokinetics of atovaquone and proguanil in pregnant women with acute falciparum malaria |
| work_keys_str_mv | AT mcgreadyr thepharmacokineticsofatovaquoneandproguanilinpregnantwomenwithacutefalciparummalaria AT stepniewskak thepharmacokineticsofatovaquoneandproguanilinpregnantwomenwithacutefalciparummalaria AT edsteinmd thepharmacokineticsofatovaquoneandproguanilinpregnantwomenwithacutefalciparummalaria AT chot thepharmacokineticsofatovaquoneandproguanilinpregnantwomenwithacutefalciparummalaria AT gilverayg thepharmacokineticsofatovaquoneandproguanilinpregnantwomenwithacutefalciparummalaria AT looareesuwans thepharmacokineticsofatovaquoneandproguanilinpregnantwomenwithacutefalciparummalaria AT whiten thepharmacokineticsofatovaquoneandproguanilinpregnantwomenwithacutefalciparummalaria AT nostenf thepharmacokineticsofatovaquoneandproguanilinpregnantwomenwithacutefalciparummalaria AT mcgreadyr pharmacokineticsofatovaquoneandproguanilinpregnantwomenwithacutefalciparummalaria AT stepniewskak pharmacokineticsofatovaquoneandproguanilinpregnantwomenwithacutefalciparummalaria AT edsteinmd pharmacokineticsofatovaquoneandproguanilinpregnantwomenwithacutefalciparummalaria AT chot pharmacokineticsofatovaquoneandproguanilinpregnantwomenwithacutefalciparummalaria AT gilverayg pharmacokineticsofatovaquoneandproguanilinpregnantwomenwithacutefalciparummalaria AT looareesuwans pharmacokineticsofatovaquoneandproguanilinpregnantwomenwithacutefalciparummalaria AT whiten pharmacokineticsofatovaquoneandproguanilinpregnantwomenwithacutefalciparummalaria AT nostenf pharmacokineticsofatovaquoneandproguanilinpregnantwomenwithacutefalciparummalaria |