Albendazole Sulfoxide Plasma Levels and Efficacy of Antiparasitic Treatment in Patients With Parenchymal Neurocysticercosis

Author:

Arroyo Gianfranco1,Bustos Javier A234,Lescano Andres G1,Gonzales Isidro4,Saavedra Herbert4,Rodriguez Silvia4,Pretell E Javier5,Bonato Pierina S6,Lanchote Vera L6,Takayanagui Osvaldo M7,Horton John8,Gonzalez Armando E9,Gilman Robert H10,Garcia Hector H234,Tsang Victor C W,O’Neal Seth,Martinez Manuel,Zimic Mirko,Verastegui Manuela,Mayta Holger,Castillo Yesenia,Lopez-Urbina Maria T,Gavidia Cesar M,Gomez-Puerta Luis A,Moyano Luz M,Gamboa Ricardo,Vilchez Percy,Muro Claudio,Nash Theodore,Mahanty Siddartha,Noh John,Handali Sukwan,Friedland Jon,

Affiliation:

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

AbstractBackgroundThe 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.MethodsASOX 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.ResultsThere 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.ConclusionsWe 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.

Funder

National Institute of Neurological Disorders and Stroke

National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

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