Pharmacokinetics of orally administered hexobarbital in plasma and saliva of healthy subjects

M van der Graaff, N P Vermeulen, P Heij, J K Boeijinga, D D Breimer

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Hexobarbital (HB) concentrations were determined in plasma and saliva of 8 healthy subjects, following oral administration of 500 mg HB-Na. Mean plasma half-lives were 3.2 +/- 0.1 h, and salivary half-lives 3.3 +/- 0.2 h. Mean plasma clearance was 22.9 +/- 2.3 1 h-1. There was a linear relationship between HB concentrations in saliva and plasma (r = 0.92). Mean salivary levels were 34 per cent of plasma levels. Salivary pH was constant throughout the experiment, 7.06 +/- 0.09. There was an inconsistent tendency of the saliva over plasma ratios to increase as a function of time. The percentage of protein binding calculated from saliva over plasma ratios was in reasonable agreement with in vitro data of equilibrium dialysis, 64.1 +/- 2.6 per cent and 65.9 +/- 0.8 per cent, respectively. The experiment was repeated in 4 subjects, and considerable intraindividual differences were shown to exist in saliva over plasma ratio, half-lives, and protein binding. It was concluded that HB elimination half-lives can relatively accurately be determined from salivary concentrations. Oral plasma clearance can only be estimated if the individual saliva over plasma ratios are known; this would require the taking of at least one blood sample during the experiment. When employing HB as a model substrate for drug metabolizing enzyme activity in vivo, the determination of its pharmacokinetic parameters, particularly oral plasma clearance as a reflection of cytochrome P-450 activity, cannot be achieved by taking saliva samples only.

Original languageEnglish
Pages (from-to)265-72
Number of pages8
JournalBiopharmaceutics & Drug Disposition
Volume7
Issue number3
DOIs
Publication statusPublished - 1 May 1986

Fingerprint

Hexobarbital
Saliva
Healthy Volunteers
Pharmacokinetics
Protein Binding
Cytochrome P-450 Enzyme System
Oral Administration
Dialysis

Keywords

  • Adult
  • Blood Proteins
  • Chromatography, Gas
  • Hexobarbital
  • Humans
  • Kinetics
  • Male
  • Protein Binding
  • Saliva
  • Journal Article

Cite this

van der Graaff, M ; Vermeulen, N P ; Heij, P ; Boeijinga, J K ; Breimer, D D. / Pharmacokinetics of orally administered hexobarbital in plasma and saliva of healthy subjects. In: Biopharmaceutics & Drug Disposition. 1986 ; Vol. 7, No. 3. pp. 265-72.
@article{37d0f6f45e2a4c17ab0bff48617bee5d,
title = "Pharmacokinetics of orally administered hexobarbital in plasma and saliva of healthy subjects",
abstract = "Hexobarbital (HB) concentrations were determined in plasma and saliva of 8 healthy subjects, following oral administration of 500 mg HB-Na. Mean plasma half-lives were 3.2 +/- 0.1 h, and salivary half-lives 3.3 +/- 0.2 h. Mean plasma clearance was 22.9 +/- 2.3 1 h-1. There was a linear relationship between HB concentrations in saliva and plasma (r = 0.92). Mean salivary levels were 34 per cent of plasma levels. Salivary pH was constant throughout the experiment, 7.06 +/- 0.09. There was an inconsistent tendency of the saliva over plasma ratios to increase as a function of time. The percentage of protein binding calculated from saliva over plasma ratios was in reasonable agreement with in vitro data of equilibrium dialysis, 64.1 +/- 2.6 per cent and 65.9 +/- 0.8 per cent, respectively. The experiment was repeated in 4 subjects, and considerable intraindividual differences were shown to exist in saliva over plasma ratio, half-lives, and protein binding. It was concluded that HB elimination half-lives can relatively accurately be determined from salivary concentrations. Oral plasma clearance can only be estimated if the individual saliva over plasma ratios are known; this would require the taking of at least one blood sample during the experiment. When employing HB as a model substrate for drug metabolizing enzyme activity in vivo, the determination of its pharmacokinetic parameters, particularly oral plasma clearance as a reflection of cytochrome P-450 activity, cannot be achieved by taking saliva samples only.",
keywords = "Adult, Blood Proteins, Chromatography, Gas, Hexobarbital, Humans, Kinetics, Male, Protein Binding, Saliva, Journal Article",
author = "{van der Graaff}, M and Vermeulen, {N P} and P Heij and Boeijinga, {J K} and Breimer, {D D}",
year = "1986",
month = "5",
day = "1",
doi = "10.1002/bdd.2510070307",
language = "English",
volume = "7",
pages = "265--72",
journal = "Biopharmaceutics & Drug Disposition",
issn = "0142-2782",
publisher = "John Wiley and Sons Ltd",
number = "3",

}

Pharmacokinetics of orally administered hexobarbital in plasma and saliva of healthy subjects. / van der Graaff, M; Vermeulen, N P; Heij, P; Boeijinga, J K; Breimer, D D.

In: Biopharmaceutics & Drug Disposition, Vol. 7, No. 3, 01.05.1986, p. 265-72.

Research output: Contribution to JournalArticleAcademicpeer-review

TY - JOUR

T1 - Pharmacokinetics of orally administered hexobarbital in plasma and saliva of healthy subjects

AU - van der Graaff, M

AU - Vermeulen, N P

AU - Heij, P

AU - Boeijinga, J K

AU - Breimer, D D

PY - 1986/5/1

Y1 - 1986/5/1

N2 - Hexobarbital (HB) concentrations were determined in plasma and saliva of 8 healthy subjects, following oral administration of 500 mg HB-Na. Mean plasma half-lives were 3.2 +/- 0.1 h, and salivary half-lives 3.3 +/- 0.2 h. Mean plasma clearance was 22.9 +/- 2.3 1 h-1. There was a linear relationship between HB concentrations in saliva and plasma (r = 0.92). Mean salivary levels were 34 per cent of plasma levels. Salivary pH was constant throughout the experiment, 7.06 +/- 0.09. There was an inconsistent tendency of the saliva over plasma ratios to increase as a function of time. The percentage of protein binding calculated from saliva over plasma ratios was in reasonable agreement with in vitro data of equilibrium dialysis, 64.1 +/- 2.6 per cent and 65.9 +/- 0.8 per cent, respectively. The experiment was repeated in 4 subjects, and considerable intraindividual differences were shown to exist in saliva over plasma ratio, half-lives, and protein binding. It was concluded that HB elimination half-lives can relatively accurately be determined from salivary concentrations. Oral plasma clearance can only be estimated if the individual saliva over plasma ratios are known; this would require the taking of at least one blood sample during the experiment. When employing HB as a model substrate for drug metabolizing enzyme activity in vivo, the determination of its pharmacokinetic parameters, particularly oral plasma clearance as a reflection of cytochrome P-450 activity, cannot be achieved by taking saliva samples only.

AB - Hexobarbital (HB) concentrations were determined in plasma and saliva of 8 healthy subjects, following oral administration of 500 mg HB-Na. Mean plasma half-lives were 3.2 +/- 0.1 h, and salivary half-lives 3.3 +/- 0.2 h. Mean plasma clearance was 22.9 +/- 2.3 1 h-1. There was a linear relationship between HB concentrations in saliva and plasma (r = 0.92). Mean salivary levels were 34 per cent of plasma levels. Salivary pH was constant throughout the experiment, 7.06 +/- 0.09. There was an inconsistent tendency of the saliva over plasma ratios to increase as a function of time. The percentage of protein binding calculated from saliva over plasma ratios was in reasonable agreement with in vitro data of equilibrium dialysis, 64.1 +/- 2.6 per cent and 65.9 +/- 0.8 per cent, respectively. The experiment was repeated in 4 subjects, and considerable intraindividual differences were shown to exist in saliva over plasma ratio, half-lives, and protein binding. It was concluded that HB elimination half-lives can relatively accurately be determined from salivary concentrations. Oral plasma clearance can only be estimated if the individual saliva over plasma ratios are known; this would require the taking of at least one blood sample during the experiment. When employing HB as a model substrate for drug metabolizing enzyme activity in vivo, the determination of its pharmacokinetic parameters, particularly oral plasma clearance as a reflection of cytochrome P-450 activity, cannot be achieved by taking saliva samples only.

KW - Adult

KW - Blood Proteins

KW - Chromatography, Gas

KW - Hexobarbital

KW - Humans

KW - Kinetics

KW - Male

KW - Protein Binding

KW - Saliva

KW - Journal Article

U2 - 10.1002/bdd.2510070307

DO - 10.1002/bdd.2510070307

M3 - Article

VL - 7

SP - 265

EP - 272

JO - Biopharmaceutics & Drug Disposition

JF - Biopharmaceutics & Drug Disposition

SN - 0142-2782

IS - 3

ER -