Effects of dosing interval on the pharmacokinetic and pharmacodynamic interactions between the oral adsorbent AST-120 and triazolam in humans.
OBJECTIVE
The objective of this study was to evaluate the pharmacokinetic and pharmacodynamic interactions between the oral adsorbent AST-120 and triazolam.


METHODS
In this randomized, cross-over study, 12 healthy volunteers received a single oral dose of triazolam 0.25 mg alone or with AST-120 2 g given 0, 30 or 60 min before triazolam administration.


RESULTS
The area under the plasma triazolam concentration-time curve (AUC(0-∞)) significantly decreased with simultaneous AST-120 + triazolam (alone vs simultaneous: 10.9 ± 6.0 vs 6.4 ± 2.6 ng·h/mL, p = 0.003). Triazolam-induced impairment in psychomotor performance assessed by the digit symbol substitution test was significantly attenuated when AST-120 was administered simultaneously. No significant changes in pharmacokinetic and pharmacodynamic parameters were observed when AST-120 was given 30 or 60 min before triazolam administration.


CONCLUSIONS
Administering AST-120 simultaneously with triazolam affects the pharmacokinetics and pharmacodynamics of triazolam. Dosing AST-120 at least 30 min before triazolam administration may avoid these interactions.
Department of Clinical Pharmacology and Therapeutics, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu-shi, Oita, 879-5593, Japan. kotet@oita-u.ac.jp
Tsutomu
T
Kotegawa
Kimiko
K
Tsutsumi
Hajime
H
Morita
Hiromistu
H
Imai
Misaki
M
Morita
Tsuneaki
T
Yoshizato
Tetsuji
T
Ohyama
Shinya
S
Uchida
Hiroshi
H
Watanabe
Noriyuki
N
Namiki
Kyoichi
K
Ohashi
D000327:Adsorption; D000328:Adult; D019540:Area Under Curve; D002244:Carbon / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D010087:Oxides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014229:Triazolam / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D055815:Young Adult
D006993:Hypnotics and Sedatives; D010087:Oxides; D014229:Triazolam; D002244:Carbon; C040896:AST 120