Efavirenz biotransformation as an up-stream event of mood changes in HIV-infected patients.
Toxicol Lett
; 260: 28-35, 2016 Oct 17.
Article
em En
| MEDLINE
| ID: mdl-27543169
ABSTRACT
Efavirenz is a drug of choice for adults and children infected with the human immunodeficiency virus. Notably, up to 35% of patients on efavirenz suffer from mood changes. This work aimed to investigate efavirenz biotransformation into 8-hydroxy-efavirenz as an up-stream event of mood changes and to evaluate the suitability of 8-hydroxy-efavirenz biomonitoring for the minimization of these manifestations. A case-control study with two age-matched groups of HIV-infected male patients was performed in a group without adverse central nervous system complaints (28 patients) and a group presenting mood changes (14 patients). The plasma concentration of non-conjugated 8-hydroxy-efavirenz was higher in patients with mood changes (p=0.020). An association between efavirenz and 8-hydroxy-efavirenz-glucuronide was found (Spearman r=0.414, p<0.010), only within therapeutic efavirenz concentrations. This correlation was not observed in patients with toxic (>4mg/L) plasma concentrations of the parent drug. We conclude that metabolism to 8-hydroxy-efavirenz is associated with efavirenz-related mood changes, which suggests that the concentration of this metabolite is a suitable parameter for therapeutic drug monitoring aimed at controlling these manifestations. Moreover, our data suggest that 8-hydroxy-efavirenz is able to cross the blood-brain barrier and that the peripheral detoxification of 8-hydroxy-efavirenz by glucuronidation may be inhibited by toxic efavirenz concentrations.
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MEDLINE
Assunto principal:
Infecções por HIV
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Monitoramento de Medicamentos
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Inibidores da Transcriptase Reversa
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Fármacos Anti-HIV
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Transtornos do Humor
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Síndromes Neurotóxicas
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Benzoxazinas
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article