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

Gianfranco Arroyo, Javier A. Bustos, Andres G. Lescano, Isidro Gonzales, Herbert Saavedra, Silvia Rodriguez, E. Javier Pretell, Pierina S. Bonato, Vera L. Lanchote, Osvaldo M. Takayanagui, John Horton, Armando E. Gonzalez, Robert H. Gilman, Hector H. Garcia, Victor C.W. Tsang, Seth O'Neal, Manuel Martinez, Mirko Zimic, Manuela Verastegui, Holger MaytaYesenia Castillo, Maria T. Lopez-Urbina, Cesar M. Gavidia, Luis A. Gomez-Puerta, Luz M. Moyano, Ricardo Gamboa, Percy Vilchez, Claudio Muro, Theodore Nash, Siddartha Mahanty, John Noh, Sukwan Handali, Jon Friedland

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Abstract

© 2019 The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. 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.
Original languageAmerican English
Pages (from-to)1996-2002
Number of pages7
JournalClinical Infectious Diseases
DOIs
StatePublished - 13 Nov 2019

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    Arroyo, G., Bustos, J. A., Lescano, A. G., Gonzales, I., Saavedra, H., Rodriguez, S., Pretell, E. J., Bonato, P. S., Lanchote, V. L., Takayanagui, O. M., Horton, J., Gonzalez, A. E., Gilman, R. H., Garcia, H. H., Tsang, V. C. W., O'Neal, S., Martinez, M., Zimic, M., Verastegui, M., ... Friedland, J. (2019). Albendazole Sulfoxide Plasma Levels and Efficacy of Antiparasitic Treatment in Patients with Parenchymal Neurocysticercosis. Clinical Infectious Diseases, 1996-2002. https://doi.org/10.1093/cid/ciz085