Maintenance time of sedative effects after an intravenous infusion of diazepam: a guide for endoscopy using diazepam.
OBJECTIVE
To examine whether the sedative effects assessed by psychomotor tests would depend on the cytochrome P450 (CYP) 2C19 genotypes after an infusion regimen of diazepam commonly used for gastrointestinal endoscopy in Japan.


METHODS
Fifteen healthy Japanese volunteers consisting of three different CYP2C19 genotype groups underwent a critical flicker fusion test, an eye movement analysis and a postural sway test as a test for physical sedative effects, and a visual analog scale (VAS) symptom assessment method as a test for mental sedative effects during the 336 h period after the intravenous infusion of diazepam (5 mg).


RESULTS
The physical sedative effects assessed by the critical flicker test continued for 1 h (t values of 5 min, 30 min and 60 min later: 4.35, 5.00 and 3.19, respectively) and those by the moving radial area of a postural sway test continued for 3 h (t values of 5 h, 30 h, 60 min and 3 h later: -4.05, -3.42, -2.17 and -2.58, respectively), which changed significantly compared with the baseline level before infusion (P<0.05). On the other hand, the mental sedative effects by the VAS method improved within 1 h. The CYP2C19 genotype-dependent differences in the postinfusion sedative effects were not observed in any of the four psychomotor function tests.


CONCLUSIONS
With the psychomotor tests, the objective sedative effects of diazepam continued for 1 h to 3 h irrespective of CYP2C19 genotype status and the subjective sedative symptoms improved within 1 h. Up to 3 h of clinical care appears to be required after the infusion of diazepam, although patients feel subjectively improved.
Sugimoto
Mitsushige
M
First Department of Medicine, Hamamatsu University School of Medicine, and Department of Gastroenterology, Enshu General Hospital, Hamamatsu, Japan. sugimoto@bcm.edu
Furuta
Takahisa
T
Nakamura
Akiko
A
Shirai
Naohito
N
Ikuma
Mutsuhiro
M
Misaka
Shingen
S
Uchida
Shinya
S
Watanabe
Hiroshi
H
Ohashi
Kyoichi
K
Ishizaki
Takashi
T
Hishida
Akira
A
D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D065731:Cytochrome P-450 CYP2C19; D003975:Diazepam / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D016099:Endoscopy, Gastrointestinal / Q000379:methods*; D005133:Eye Movements / Q000187:drug effects / Q000502:physiology; D005260:Female; D005425:Flicker Fusion / Q000187:drug effects; D005838:Genotype; D017408:Guidelines as Topic; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008297:Male; D011187:Posture / Q000502:physiology; D011597:Psychomotor Performance / Q000187:drug effects*; D013997:Time Factors
D006993:Hypnotics and Sedatives; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D003975:Diazepam
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