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Pharmacokinetics of orally administered hexobarbital in plasma and saliva of healthy subjects
Author(s) -
Van Der Graaff M.,
Vermeulen N. P. E.,
Heij P.,
Boeijinga J. K.,
Breimer D. D.
Publication year - 1986
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2510070307
Subject(s) - pharmacokinetics , saliva , pharmacology , hexobarbital , oral dose , oral administration , medicine , plasma concentration , plasma levels , chemistry , biochemistry , in vitro , microsome
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 1h −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, repectively. 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.