Efavirenz-induced neurological symptoms in rare homozygote CYP2B6 *2/*2 (C64T).
Some of the HIV-1-infected patients who were given highly active anti-retroviral therapy (HAART) including efavirenz (EFV) presented adverse central nervous system (CNS) symptoms such as fatigue and insomnia. The incidence of adverse CNS symptoms is associated with hepatic cytochrome P450 isozymes (CYP2B6) polymorphisms. For example, CYP2B6 *6 (G516T and A785G) and *7 (G516T, A785G and C1459T) prolonged the EFV half-life despite discontinuation of EFV. CYP2B6 *2/*2 (C64T) is extremely rare and there have been no data describing the EFV plasma concentrations in C64T homozygous patients, who developed adverse CNS symptoms. C64T homozygous possibly has some catalytic defects.
Usami
Osamu
O
Division of Infectious and Respiratory Diseases, Internal Medicine, Tohoku University, Seiryo-cyo 1-1, Aoba-ku, Sendai-si, Miyagi-ken, 960-8574 Sendai, Japan. usami@rid.med.tohoku.ac.jp
Ashino
Yugo
Y
Komaki
Yuichi
Y
Tomaki
Masafumi
M
Irokawa
Toshiya
T
Tamada
Tsutomu
T
Hayashida
Tsunefusa
T
Teruya
Katsuji
K
Hattori
Toshio
T
D000480:Alkynes; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D048588:Benzoxazines / Q000009:adverse effects* / Q000378:metabolism; D003521:Cyclopropanes; D065702:Cytochrome P-450 CYP2B6; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000187:drug effects*; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects* / Q000378:metabolism
D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; D010089:Oxidoreductases, N-Demethylating; C098320:efavirenz