Arroyo Gianfranco, Bustos Javier A, Lescano Andres G, Gonzales Isidro, Saavedra Herbert, Rodriguez Silvia, Pretell E Javier, Bonato Pierina S, Lanchote Vera L, Takayanagui Osvaldo M, Horton John, Gonzalez Armando E, Gilman Robert H, Garcia Hector H
School of Public Health and Administration, Lima.
Department of Microbiology, School of Sciences, Lima.
Clin Infect Dis. 2019 Nov 13;69(11):1996-2002. doi: 10.1093/cid/ciz085.
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.
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.
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.
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.
阿苯达唑治疗实质性神经囊尾蚴病(NCC)患者的疗效欠佳。阿苯达唑的活性代谢产物阿苯达唑亚砜(ASOX)的血浆水平在患者中差异很大。我们推测,阿苯达唑治疗期间ASOX血浆水平较高可能与抗寄生虫疗效增加有关。
在一项治疗试验中,对118例实质性NCC患者在治疗第7天测量ASOX血浆水平。评估ASOX血浆水平升高与囊肿消退比例以及完全囊肿消退患者比例(通过6个月脑磁共振评估)之间的关系。
随着ASOX血浆水平四分位数的增加,囊肿消退比例和治愈患者比例有升高趋势。在有3个或更多脑囊肿的患者中,经吡喹酮(PZQ)联合给药调整后的回归分析显示,当比较最高四分位数与最低四分位数的ASOX水平时,囊肿消退比例增加2倍(风险比[RR],1.98;95%置信区间[CI],1.01 - 3.89;P = 0.048),治愈患者比例增加2.5倍(RR,2.45;95% CI,0.94 - 6.36;P = 0.067)。在有1 - 2个脑囊肿的患者中未发现相关性。
我们认为实质性NCC患者中ASOX血浆水平高与抗寄生虫疗效增加之间存在关联。尽管如此,这种关联也受其他因素影响,包括寄生虫负荷和PZQ联合给药。这些发现可能有助于个体化和/或调整治疗方案以避免治疗失败。