Single and multiple dose pharmacokinetics of etizolam in healthy subjects

C. Fracasso, S. Confalonieri, S. Garattini, S. Caccia

Research output: Contribution to journalArticle

Abstract

The pharmacokinetics of etizolam, a new thienodiazepine derivative, has been examined after single and multiple (0.5 mg tablet) (0.5 mg b.d for 1 week) oral therapeutic doses in healthy volunteers. The single-dose kinetic profile of etizolam suggested that absorption after oral dosage was reasonably rapid, the maximum plasma concentration (Cmax) being attained within 0.5-2 h in all subjects. The mean elimination half-life (t1/2) averaged 3.4 h. Consistent with this, steady-state concentration were rapidly achieved and accumulation was extremely limited. Predicted average plasma concentrations (Cp) did not differ significantly from those actually measured at steady-state, suggesting that the kinetics of etizolam was linear, at least at therapeutic doses. The mean wash-out t1/2 was comparable to the elimination t1/2 of the single dose, which means that the drug probably has no effect on hepatic microsomal enzymes and other kinetic variables after repeated dosing. At steady state plasma concentrations of the main metabolite, α-hydroxyetizolam, were higher and disappeared more slowly (mean t1/2 8.2 h) than those of the parent compound. Taken with the fact that in animals the metabolite shows almost the same potency of pharmacological action as etizolam, this suggests that it may contribute significantly to the clinical effects of the parent compound. Based on the kinetic characteristics of the parent drug and its metabolite, etizolam can be regarded as a short-acting benzodiazepine, with elimination kinetics between those of short-intermediate derivatives and ultra-rapidly eliminated benzodiazepines.

Original languageEnglish
Pages (from-to)181-185
Number of pages5
JournalEuropean Journal of Clinical Pharmacology
Volume40
Issue number2
DOIs
Publication statusPublished - Feb 1991

Fingerprint

Healthy Volunteers
Pharmacokinetics
Benzodiazepines
Pharmaceutical Preparations
Tablets
Half-Life
Parents
etizolam
Pharmacology
Liver
Enzymes
Therapeutics

Keywords

  • α-hydroxyetizolam
  • Etizolam
  • healthy subjects
  • kinetics

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Pharmacology (medical)

Cite this

Single and multiple dose pharmacokinetics of etizolam in healthy subjects. / Fracasso, C.; Confalonieri, S.; Garattini, S.; Caccia, S.

In: European Journal of Clinical Pharmacology, Vol. 40, No. 2, 02.1991, p. 181-185.

Research output: Contribution to journalArticle

Fracasso, C. ; Confalonieri, S. ; Garattini, S. ; Caccia, S. / Single and multiple dose pharmacokinetics of etizolam in healthy subjects. In: European Journal of Clinical Pharmacology. 1991 ; Vol. 40, No. 2. pp. 181-185.
@article{e2508514529a4eb79c4fca8aacd5392f,
title = "Single and multiple dose pharmacokinetics of etizolam in healthy subjects",
abstract = "The pharmacokinetics of etizolam, a new thienodiazepine derivative, has been examined after single and multiple (0.5 mg tablet) (0.5 mg b.d for 1 week) oral therapeutic doses in healthy volunteers. The single-dose kinetic profile of etizolam suggested that absorption after oral dosage was reasonably rapid, the maximum plasma concentration (Cmax) being attained within 0.5-2 h in all subjects. The mean elimination half-life (t1/2) averaged 3.4 h. Consistent with this, steady-state concentration were rapidly achieved and accumulation was extremely limited. Predicted average plasma concentrations (Cp) did not differ significantly from those actually measured at steady-state, suggesting that the kinetics of etizolam was linear, at least at therapeutic doses. The mean wash-out t1/2 was comparable to the elimination t1/2 of the single dose, which means that the drug probably has no effect on hepatic microsomal enzymes and other kinetic variables after repeated dosing. At steady state plasma concentrations of the main metabolite, α-hydroxyetizolam, were higher and disappeared more slowly (mean t1/2 8.2 h) than those of the parent compound. Taken with the fact that in animals the metabolite shows almost the same potency of pharmacological action as etizolam, this suggests that it may contribute significantly to the clinical effects of the parent compound. Based on the kinetic characteristics of the parent drug and its metabolite, etizolam can be regarded as a short-acting benzodiazepine, with elimination kinetics between those of short-intermediate derivatives and ultra-rapidly eliminated benzodiazepines.",
keywords = "α-hydroxyetizolam, Etizolam, healthy subjects, kinetics",
author = "C. Fracasso and S. Confalonieri and S. Garattini and S. Caccia",
year = "1991",
month = "2",
doi = "10.1007/BF00280074",
language = "English",
volume = "40",
pages = "181--185",
journal = "European Journal of Clinical Pharmacology",
issn = "0031-6970",
publisher = "Springer Verlag",
number = "2",

}

TY - JOUR

T1 - Single and multiple dose pharmacokinetics of etizolam in healthy subjects

AU - Fracasso, C.

AU - Confalonieri, S.

AU - Garattini, S.

AU - Caccia, S.

PY - 1991/2

Y1 - 1991/2

N2 - The pharmacokinetics of etizolam, a new thienodiazepine derivative, has been examined after single and multiple (0.5 mg tablet) (0.5 mg b.d for 1 week) oral therapeutic doses in healthy volunteers. The single-dose kinetic profile of etizolam suggested that absorption after oral dosage was reasonably rapid, the maximum plasma concentration (Cmax) being attained within 0.5-2 h in all subjects. The mean elimination half-life (t1/2) averaged 3.4 h. Consistent with this, steady-state concentration were rapidly achieved and accumulation was extremely limited. Predicted average plasma concentrations (Cp) did not differ significantly from those actually measured at steady-state, suggesting that the kinetics of etizolam was linear, at least at therapeutic doses. The mean wash-out t1/2 was comparable to the elimination t1/2 of the single dose, which means that the drug probably has no effect on hepatic microsomal enzymes and other kinetic variables after repeated dosing. At steady state plasma concentrations of the main metabolite, α-hydroxyetizolam, were higher and disappeared more slowly (mean t1/2 8.2 h) than those of the parent compound. Taken with the fact that in animals the metabolite shows almost the same potency of pharmacological action as etizolam, this suggests that it may contribute significantly to the clinical effects of the parent compound. Based on the kinetic characteristics of the parent drug and its metabolite, etizolam can be regarded as a short-acting benzodiazepine, with elimination kinetics between those of short-intermediate derivatives and ultra-rapidly eliminated benzodiazepines.

AB - The pharmacokinetics of etizolam, a new thienodiazepine derivative, has been examined after single and multiple (0.5 mg tablet) (0.5 mg b.d for 1 week) oral therapeutic doses in healthy volunteers. The single-dose kinetic profile of etizolam suggested that absorption after oral dosage was reasonably rapid, the maximum plasma concentration (Cmax) being attained within 0.5-2 h in all subjects. The mean elimination half-life (t1/2) averaged 3.4 h. Consistent with this, steady-state concentration were rapidly achieved and accumulation was extremely limited. Predicted average plasma concentrations (Cp) did not differ significantly from those actually measured at steady-state, suggesting that the kinetics of etizolam was linear, at least at therapeutic doses. The mean wash-out t1/2 was comparable to the elimination t1/2 of the single dose, which means that the drug probably has no effect on hepatic microsomal enzymes and other kinetic variables after repeated dosing. At steady state plasma concentrations of the main metabolite, α-hydroxyetizolam, were higher and disappeared more slowly (mean t1/2 8.2 h) than those of the parent compound. Taken with the fact that in animals the metabolite shows almost the same potency of pharmacological action as etizolam, this suggests that it may contribute significantly to the clinical effects of the parent compound. Based on the kinetic characteristics of the parent drug and its metabolite, etizolam can be regarded as a short-acting benzodiazepine, with elimination kinetics between those of short-intermediate derivatives and ultra-rapidly eliminated benzodiazepines.

KW - α-hydroxyetizolam

KW - Etizolam

KW - healthy subjects

KW - kinetics

UR - http://www.scopus.com/inward/record.url?scp=0025979301&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025979301&partnerID=8YFLogxK

U2 - 10.1007/BF00280074

DO - 10.1007/BF00280074

M3 - Article

C2 - 2065698

AN - SCOPUS:0025979301

VL - 40

SP - 181

EP - 185

JO - European Journal of Clinical Pharmacology

JF - European Journal of Clinical Pharmacology

SN - 0031-6970

IS - 2

ER -