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 Emiliano Gonzalez Zariquiey, Robert H. Gilman, Hector H. Garcia, Victor C.W. Tsang, Seth O'Neal, Manuel Martinez, Mirko Zimic, Manuela Verastegui, Holger MaytaYesenia Castillo, Maria Teresa Lopez Urbina, Cesar Miguel Gavidia Chucan, Luis Antonio Gomez Puerta, Luz M. Moyano, Ricardo Gamboa, Percy Vilchez, Claudio Muro, Theodore Nash, Siddartha Mahanty, John Noh, Sukwan Handali, Jon Friedland

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish
Pages (from-to)1996-2002
Number of pages7
JournalClinical Infectious Diseases
Volume69
Issue number11
DOIs
StatePublished - 13 Nov 2019

Bibliographical note

Funding Information:
Financial support. Data analyzed in this study were obtained from the primary study funded by the National Institute of Neurological Disorders and Stroke, US National Institutes of Health (NIH; grants NS054805 and NS086968). G.A. is a doctoral student studying epidemiological research at the Universidad Peruana Cayetano Heredia sponsored by the National Council for Science, Technology, and Innovation of Peru (CONCYTEC/ CIENCIA ACTIVA, scholarship EF033-235-2015) and is supported by training grants D43TW001140 and D43TW007393 awarded by the Fogarty International Center of the NIH.

Funding Information:
The authors thank Jessica Del Carpio, Monica Vera, Karina Fernandez, and the team of clinical coordinators for their enormous effort in the development of the primary study. They also thank all members of the Cysticercosis Working Group in Peru whose suggestions and recommendations contributed to the improvement of the present work. Data analyzed in this study were obtained from the primary study funded by the National Institute of Neurological Disorders and Stroke, US National Institutes of Health (NIH; grants NS054805 and NS086968). G.A. is a doctoral student studying epidemiological research at the Universidad Peruana Cayetano Heredia sponsored by the National Council for Science, Technology, and Innovation of Peru (CONCYTEC/ CIENCIA ACTIVA, scholarship EF033-235-2015) and is supported by training grants D43TW001140 and D43TW007393 awarded by the Fogarty International Center of the NIH.

Keywords

  • albendazole
  • albendazole sulfoxide
  • neurocysticercosis
  • praziquantel

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