Hemolytic Potential of Tafenoquine in Female Volunteers Heterozygous for Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency (
| Autor: | Ronnatrai, Rueangweerayut, Germana, Bancone, Emma J, Harrell, Andrew P, Beelen, Supornchai, Kongpatanakul, Jörg J, Möhrle, Vicki, Rousell, Khadeeja, Mohamed, Ammar, Qureshi, Sushma, Narayan, Nushara, Yubon, Ann, Miller, François H, Nosten, Lucio, Luzzatto, Stephan, Duparc, Jörg-Peter, Kleim, Justin A, Green |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Heterozygote Adolescent Dose-Response Relationship Drug Articles Glucosephosphate Dehydrogenase Middle Aged Gene Expression Regulation Enzymologic Antimalarials Young Adult Glucosephosphate Dehydrogenase Deficiency hemic and lymphatic diseases Case-Control Studies parasitic diseases Aminoquinolines Humans Female |
| Zdroj: | The American Journal of Tropical Medicine and Hygiene |
| ISSN: | 1476-1645 |
| Popis: | Tafenoquine is an 8-aminoquinoline under investigation for the prevention of relapse in Plasmodium vivax malaria. This open-label, dose-escalation study assessed quantitatively the hemolytic risk with tafenoquine in female healthy volunteers heterozygous for the Mahidol487A glucose-6-phosphate dehydrogenase (G6PD)-deficient variant versus G6PD-normal females, and with reference to primaquine. Six G6PD-heterozygous subjects (G6PD enzyme activity 40–60% of normal) and six G6PD-normal subjects per treatment group received single-dose tafenoquine (100, 200, or 300 mg) or primaquine (15 mg × 14 days). All participants had pretreatment hemoglobin levels ≥ 12.0 g/dL. Tafenoquine dose escalation stopped when hemoglobin decreased by ≥ 2.5 g/dL (or hematocrit decline ≥ 7.5%) versus pretreatment values in ≥ 3/6 subjects. A dose–response was evident in G6PD-heterozygous subjects (N = 15) receiving tafenoquine for the maximum decrease in hemoglobin versus pretreatment values. Hemoglobin declines were similar for tafenoquine 300 mg (−2.65 to −2.95 g/dL [N = 3]) and primaquine (−1.25 to −3.0 g/dL [N = 5]). Two further cohorts of G6PD-heterozygous subjects with G6PD enzyme levels 61–80% (N = 2) and > 80% (N = 5) of the site median normal received tafenoquine 200 mg; hemolysis was less pronounced at higher G6PD enzyme activities. Tafenoquine hemolytic potential was dose dependent, and hemolysis was greater in G6PD-heterozygous females with lower G6PD enzyme activity levels. Single-dose tafenoquine 300 mg did not appear to increase the severity of hemolysis versus primaquine 15 mg × 14 days. |
| Databáze: | OpenAIRE |
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