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 Mayta; Yesenia 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

doi:10.1093/cid/ciz085

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

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 language	English
Pages (from-to)	1996-2002
Number of pages	7
Journal	Clinical Infectious Diseases
Volume	69
Issue number	11
DOIs	https://doi.org/10.1093/cid/ciz085
State	Published - 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.

Publisher Copyright:
© 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.

Keywords

albendazole
albendazole sulfoxide
neurocysticercosis
praziquantel

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10.1093/cid/ciz085

Cite this

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, 69(11), 1996-2002. https://doi.org/10.1093/cid/ciz085

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title = "Albendazole Sulfoxide Plasma Levels and Efficacy of Antiparasitic Treatment in Patients with Parenchymal Neurocysticercosis",

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.",

keywords = "albendazole, albendazole sulfoxide, neurocysticercosis, praziquantel",

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

note = "Publisher Copyright: {\textcopyright} 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.",

year = "2019",

month = nov,

day = "13",

doi = "10.1093/cid/ciz085",

language = "Ingl{\'e}s",

volume = "69",

pages = "1996--2002",

journal = "Clinical Infectious Diseases",

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Arroyo, G, Bustos, JA, Lescano, AG, Gonzales, I, Saavedra, H, Rodriguez, S, Pretell, EJ, Bonato, PS, Lanchote, VL, Takayanagui, OM, Horton, J, Gonzalez, AE, Gilman, RH, Garcia, HH, Tsang, VCW, O'Neal, S, Martinez, M, Zimic, M, Verastegui, M, Mayta, H, Castillo, Y, Lopez-Urbina, MT , Gavidia, CM , Gomez-Puerta, LA, Moyano, LM, Gamboa, R, Vilchez, P, Muro, C, Nash, T, Mahanty, S, Noh, J, Handali, S & Friedland, J 2019, 'Albendazole Sulfoxide Plasma Levels and Efficacy of Antiparasitic Treatment in Patients with Parenchymal Neurocysticercosis', Clinical Infectious Diseases, vol. 69, no. 11, pp. 1996-2002. https://doi.org/10.1093/cid/ciz085

TY - JOUR

T1 - Albendazole Sulfoxide Plasma Levels and Efficacy of Antiparasitic Treatment in Patients with Parenchymal Neurocysticercosis

AU - Arroyo, Gianfranco

AU - Bustos, Javier A.

AU - Lescano, Andres G.

AU - Gonzales, Isidro

AU - Saavedra, Herbert

AU - Rodriguez, Silvia

AU - Pretell, E. Javier

AU - Bonato, Pierina S.

AU - Lanchote, Vera L.

AU - Takayanagui, Osvaldo M.

AU - Horton, John

AU - Gonzalez, Armando E.

AU - Gilman, Robert H.

AU - Garcia, Hector H.

AU - Tsang, Victor C.W.

AU - O'Neal, Seth

AU - Martinez, Manuel

AU - Zimic, Mirko

AU - Verastegui, Manuela

AU - Mayta, Holger

AU - Castillo, Yesenia

AU - Lopez-Urbina, Maria T.

AU - Gavidia, Cesar M.

AU - Gomez-Puerta, Luis A.

AU - Moyano, Luz M.

AU - Gamboa, Ricardo

AU - Vilchez, Percy

AU - Muro, Claudio

AU - Nash, Theodore

AU - Mahanty, Siddartha

AU - Noh, John

AU - Handali, Sukwan

AU - Friedland, Jon

N1 - Publisher Copyright: © 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.

PY - 2019/11/13

Y1 - 2019/11/13

N2 - 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.

AB - 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.

KW - albendazole

KW - albendazole sulfoxide

KW - neurocysticercosis

KW - praziquantel

UR - http://www.scopus.com/inward/record.url?scp=85075037234&partnerID=8YFLogxK

U2 - 10.1093/cid/ciz085

DO - 10.1093/cid/ciz085

M3 - Artículo

C2 - 30715265

AN - SCOPUS:85075037234

SN - 1058-4838

VL - 69

SP - 1996

EP - 2002

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

IS - 11

ER -

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

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