The Influence of Obesity on the Pharmacokinetics of Oral Alprazolam and Triazolam

Darrell R. Abernethy, David J. Greenblatt, Marcia Divoll, Randall B. Smith, Richard I. Shader

Research output: Contribution to journalArticle

Abstract

12 obese patients, pair-matched with 12 normal subjects, received a single 1mg oral dose of alprazolam. Nine similar subject pairs received a single 0.5mg oral dose of triazolam. Oral volume of distribution (Vd) was much greater in obese than control subjects for alprazolam (mean 114 vs 73L, p <0.001), but there was no difference between the 2 groups for triazolam (117 vs 116L). Apparent oral clearance (not corrected for body weight) of alprazolam was lower, although not significantly so, in obesity (66 vs 88 ml/min), but for triazolam it was much lower in the obese (340 vs 531 ml/min, p <0.005). Elimination half-life, which is dependent on both Vd and clearance, was prolonged in obesity for alprazolam (22 vs 11h, p <0.001) due to the increase in Vd, and also for triazolam (4.1 vs 2.6h, p <0.025) because of the decreased clearance. Plasma protein binding was unchanged in obese compared with control subjects for both alprazolam and triazolam. During long term administration alprazolam should therefore take longer to reach steady-state concentrations in obese patients but the final levels achieved should be no different than for patients of normal bodyweight, provided dosage is adjusted for ideal rather than total bodyweight. In contrast, triazolam has impaired clearance in obesity. However, if given once-daily it still would not accumulate with long term dosing due to its short half-life relative to the interval between doses.

Original languageEnglish (US)
Pages (from-to)177-183
Number of pages7
JournalClinical Pharmacokinetics
Volume9
Issue number2
DOIs
StatePublished - 1984
Externally publishedYes

Fingerprint

Triazolam
Alprazolam
Pharmacokinetics
Obesity
Half-Life
Protein Binding
Blood Proteins
Body Weight

ASJC Scopus subject areas

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

Cite this

Abernethy, D. R., Greenblatt, D. J., Divoll, M., Smith, R. B., & Shader, R. I. (1984). The Influence of Obesity on the Pharmacokinetics of Oral Alprazolam and Triazolam. Clinical Pharmacokinetics, 9(2), 177-183. https://doi.org/10.2165/00003088-198409020-00005

The Influence of Obesity on the Pharmacokinetics of Oral Alprazolam and Triazolam. / Abernethy, Darrell R.; Greenblatt, David J.; Divoll, Marcia; Smith, Randall B.; Shader, Richard I.

In: Clinical Pharmacokinetics, Vol. 9, No. 2, 1984, p. 177-183.

Research output: Contribution to journalArticle

Abernethy, DR, Greenblatt, DJ, Divoll, M, Smith, RB & Shader, RI 1984, 'The Influence of Obesity on the Pharmacokinetics of Oral Alprazolam and Triazolam', Clinical Pharmacokinetics, vol. 9, no. 2, pp. 177-183. https://doi.org/10.2165/00003088-198409020-00005
Abernethy, Darrell R. ; Greenblatt, David J. ; Divoll, Marcia ; Smith, Randall B. ; Shader, Richard I. / The Influence of Obesity on the Pharmacokinetics of Oral Alprazolam and Triazolam. In: Clinical Pharmacokinetics. 1984 ; Vol. 9, No. 2. pp. 177-183.
@article{9abd3304b34b4bdd863fde3b17091b53,
title = "The Influence of Obesity on the Pharmacokinetics of Oral Alprazolam and Triazolam",
abstract = "12 obese patients, pair-matched with 12 normal subjects, received a single 1mg oral dose of alprazolam. Nine similar subject pairs received a single 0.5mg oral dose of triazolam. Oral volume of distribution (Vd) was much greater in obese than control subjects for alprazolam (mean 114 vs 73L, p <0.001), but there was no difference between the 2 groups for triazolam (117 vs 116L). Apparent oral clearance (not corrected for body weight) of alprazolam was lower, although not significantly so, in obesity (66 vs 88 ml/min), but for triazolam it was much lower in the obese (340 vs 531 ml/min, p <0.005). Elimination half-life, which is dependent on both Vd and clearance, was prolonged in obesity for alprazolam (22 vs 11h, p <0.001) due to the increase in Vd, and also for triazolam (4.1 vs 2.6h, p <0.025) because of the decreased clearance. Plasma protein binding was unchanged in obese compared with control subjects for both alprazolam and triazolam. During long term administration alprazolam should therefore take longer to reach steady-state concentrations in obese patients but the final levels achieved should be no different than for patients of normal bodyweight, provided dosage is adjusted for ideal rather than total bodyweight. In contrast, triazolam has impaired clearance in obesity. However, if given once-daily it still would not accumulate with long term dosing due to its short half-life relative to the interval between doses.",
author = "Abernethy, {Darrell R.} and Greenblatt, {David J.} and Marcia Divoll and Smith, {Randall B.} and Shader, {Richard I.}",
year = "1984",
doi = "10.2165/00003088-198409020-00005",
language = "English (US)",
volume = "9",
pages = "177--183",
journal = "Clinical Pharmacokinetics",
issn = "0312-5963",
publisher = "Adis International Ltd",
number = "2",

}

TY - JOUR

T1 - The Influence of Obesity on the Pharmacokinetics of Oral Alprazolam and Triazolam

AU - Abernethy, Darrell R.

AU - Greenblatt, David J.

AU - Divoll, Marcia

AU - Smith, Randall B.

AU - Shader, Richard I.

PY - 1984

Y1 - 1984

N2 - 12 obese patients, pair-matched with 12 normal subjects, received a single 1mg oral dose of alprazolam. Nine similar subject pairs received a single 0.5mg oral dose of triazolam. Oral volume of distribution (Vd) was much greater in obese than control subjects for alprazolam (mean 114 vs 73L, p <0.001), but there was no difference between the 2 groups for triazolam (117 vs 116L). Apparent oral clearance (not corrected for body weight) of alprazolam was lower, although not significantly so, in obesity (66 vs 88 ml/min), but for triazolam it was much lower in the obese (340 vs 531 ml/min, p <0.005). Elimination half-life, which is dependent on both Vd and clearance, was prolonged in obesity for alprazolam (22 vs 11h, p <0.001) due to the increase in Vd, and also for triazolam (4.1 vs 2.6h, p <0.025) because of the decreased clearance. Plasma protein binding was unchanged in obese compared with control subjects for both alprazolam and triazolam. During long term administration alprazolam should therefore take longer to reach steady-state concentrations in obese patients but the final levels achieved should be no different than for patients of normal bodyweight, provided dosage is adjusted for ideal rather than total bodyweight. In contrast, triazolam has impaired clearance in obesity. However, if given once-daily it still would not accumulate with long term dosing due to its short half-life relative to the interval between doses.

AB - 12 obese patients, pair-matched with 12 normal subjects, received a single 1mg oral dose of alprazolam. Nine similar subject pairs received a single 0.5mg oral dose of triazolam. Oral volume of distribution (Vd) was much greater in obese than control subjects for alprazolam (mean 114 vs 73L, p <0.001), but there was no difference between the 2 groups for triazolam (117 vs 116L). Apparent oral clearance (not corrected for body weight) of alprazolam was lower, although not significantly so, in obesity (66 vs 88 ml/min), but for triazolam it was much lower in the obese (340 vs 531 ml/min, p <0.005). Elimination half-life, which is dependent on both Vd and clearance, was prolonged in obesity for alprazolam (22 vs 11h, p <0.001) due to the increase in Vd, and also for triazolam (4.1 vs 2.6h, p <0.025) because of the decreased clearance. Plasma protein binding was unchanged in obese compared with control subjects for both alprazolam and triazolam. During long term administration alprazolam should therefore take longer to reach steady-state concentrations in obese patients but the final levels achieved should be no different than for patients of normal bodyweight, provided dosage is adjusted for ideal rather than total bodyweight. In contrast, triazolam has impaired clearance in obesity. However, if given once-daily it still would not accumulate with long term dosing due to its short half-life relative to the interval between doses.

UR - http://www.scopus.com/inward/record.url?scp=0021351710&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0021351710&partnerID=8YFLogxK

U2 - 10.2165/00003088-198409020-00005

DO - 10.2165/00003088-198409020-00005

M3 - Article

C2 - 6143633

AN - SCOPUS:0021351710

VL - 9

SP - 177

EP - 183

JO - Clinical Pharmacokinetics

JF - Clinical Pharmacokinetics

SN - 0312-5963

IS - 2

ER -