Gianfranco Arroyo1, Javier A Bustos2,3,4, Andres G Lescano1, Isidro Gonzales4, Herbert Saavedra4, Silvia Rodriguez4, E Javier Pretell5, Pierina S Bonato6, Vera L Lanchote6, Osvaldo M Takayanagui7, John Horton8, Armando E Gonzalez9, Robert H Gilman10, Hector H Garcia2,3,4. 1. School of Public Health and Administration, Lima. 2. Department of Microbiology, School of Sciences, Lima. 3. Center for Global Health, Universidad Peruana Cayetano Heredia, Lima. 4. Cysticercosis Unit, Instituto Nacional de Ciencias Neurológicas, Lima. 5. Department of Neurology, Hospital Alberto Sabogal, Callao, Peru. 6. Faculdade de Ciências Farmacêuticas de Ribeirão Preto, United Kingdom. 7. Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo Brasil, United Kingdom. 8. Tropical Projects, Hitchin, United Kingdom. 9. School of Veterinary Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru. 10. Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland.
Abstract
BACKGROUND: The efficacy of albendazole therapy in patients with parenchymal neurocysticercosis (NCC) is suboptimal. Plasma levels of albendazole sulfoxide (ASOX), the active metabolite of albendazole, are highly variable among patients. We hypothesized that high ASOX plasma levels during albendazole therapy may be associated with an increased antiparasitic efficacy. METHODS: ASOX plasma levels were measured at treatment day 7 in 118 patients with parenchymal NCC enrolled in a treatment trial. The relationships between increasing ASOX plasma levels with the proportion of cysts resolved and the proportion of patients with complete cyst resolution (evaluated by 6-month brain magnetic resonance) were assessed. RESULTS: There was a trend toward a higher proportion of cysts resolved and a higher proportion of patients cured with increasing quartiles of ASOX plasma levels. In patients with 3 or more brain cysts, the regression analysis adjusted by the concomitant administration of praziquantel (PZQ) showed a 2-fold increase in the proportion of cysts resolved (risk ratio [RR], 1.98; 95% confidence interval [CI], 1.01-3.89; P = .048) and 2.5-fold increase in the proportion of patients cured (RR, 2.45; 95% CI, .94-6.36; P = .067) when ASOX levels in the highest vs the lowest quartile were compared. No association was found in patients with 1-2 brain cysts. CONCLUSIONS: We suggest an association between high ASOX plasma levels and increased antiparasitic efficacy in patients with parenchymal NCC. Nonetheless, this association is also influenced by other factors including parasite burden and concomitant administration of PZQ. These findings may serve to individualize and/or adjust therapy schemes to avoid treatment failure.
BACKGROUND: The efficacy of albendazole therapy in patients with parenchymal neurocysticercosis (NCC) is suboptimal. Plasma levels of albendazole sulfoxide (ASOX), the active metabolite of albendazole, are highly variable among patients. We hypothesized that high ASOX plasma levels during albendazole therapy may be associated with an increased antiparasitic efficacy. METHODS:ASOX plasma levels were measured at treatment day 7 in 118 patients with parenchymal NCC enrolled in a treatment trial. The relationships between increasing ASOX plasma levels with the proportion of cysts resolved and the proportion of patients with complete cyst resolution (evaluated by 6-month brain magnetic resonance) were assessed. RESULTS: There was a trend toward a higher proportion of cysts resolved and a higher proportion of patients cured with increasing quartiles of ASOX plasma levels. In patients with 3 or more brain cysts, the regression analysis adjusted by the concomitant administration of praziquantel (PZQ) showed a 2-fold increase in the proportion of cysts resolved (risk ratio [RR], 1.98; 95% confidence interval [CI], 1.01-3.89; P = .048) and 2.5-fold increase in the proportion of patients cured (RR, 2.45; 95% CI, .94-6.36; P = .067) when ASOX levels in the highest vs the lowest quartile were compared. No association was found in patients with 1-2 brain cysts. CONCLUSIONS: We suggest an association between high ASOX plasma levels and increased antiparasitic efficacy in patients with parenchymal NCC. Nonetheless, this association is also influenced by other factors including parasite burden and concomitant administration of PZQ. These findings may serve to individualize and/or adjust therapy schemes to avoid treatment failure.
Authors: N Castro; C Márquez-Caraveo; R C Brundage; D González-Esquivel; A M Suárez; F Góngora; A Jara; J Urizar; J M Lanao; H Jung Journal: Int J Clin Pharmacol Ther Date: 2009-11 Impact factor: 1.366
Authors: Hector H Garcia; Andres G Lescano; Vera L Lanchote; E Javier Pretell; Isidro Gonzales; Javier A Bustos; Osvaldo M Takayanagui; Pierina S Bonato; John Horton; Herbert Saavedra; Armando E Gonzalez; Robert H Gilman Journal: Br J Clin Pharmacol Date: 2011-07 Impact factor: 4.335
Authors: Renata Monteiro Lima; Maria Augusta Drago Ferreira; Teresa Maria de Jesus Ponte Carvalho; Bruno José Dumêt Fernandes; Osvaldo Massaiti Takayanagui; Hector Hugo Garcia; Eduardo Barbosa Coelho; Vera Lucia Lanchote Journal: Br J Clin Pharmacol Date: 2011-04 Impact factor: 4.335