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

✍ Scribed by M. Van Der Graaff; N. P. E. Vermeulen; P. Heij; J. K. Boeijinga; D. D. Breimer

• Publisher: John Wiley and Sons
• Year: 1986
• Tongue: English
• Weight: 375 KB
• Volume: 7
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/bdd.2510070307

✦ Synopsis

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 k 0.1 h, and salivary half-lives 3.3 k 0.2 h. Mean plasma clearance was 22.9 k 2.3 1 h-'. There was a linear relationship between H B 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 f 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 ?c 2.6 per cent and 65.9 k 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 H B 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 irz 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.