Adult age and ex vivo protein binding of lorazepam, oxazepam and temazepam in healthy subjects
Article first published online: 9 NOV 2011
© 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society
British Journal of Clinical Pharmacology
Volume 72, Issue 6, pages 985–989, December 2011
How to Cite
Chin, P. K. L., Jensen, B. P., Larsen, H. S. and Begg, E. J. (2011), Adult age and ex vivo protein binding of lorazepam, oxazepam and temazepam in healthy subjects. British Journal of Clinical Pharmacology, 72: 985–989. doi: 10.1111/j.1365-2125.2011.04036.x
- Issue published online: 9 NOV 2011
- Article first published online: 9 NOV 2011
- Accepted manuscript online: 14 JUN 2011 10:11AM EST
- Received; 13 March 2011; Accepted; 2 June 2011; Accepted Article; 14 June 2011
- protein binding;
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
• The hypothesis that protein binding decreases with ageing has been used to explain studies that have not found a decline in total clearance in relation to age of highly protein bound drugs, cleared by capacity limited metabolism.
• Lorazepam, oxazepam and temazepam are highly protein bound to albumin and are cleared by capacity limited metabolism.
• There is conflicting or little data concerning the relationship between the protein binding of these drugs and age.
WHAT THIS PAPER ADDS
• In an ex vivo study of 60 healthy subjects (19–87 years), no clinically significant change was seen in the protein binding of these benzodiazepines with age, arguing against the hypothesis, at least in healthy subjects. The study was adequately powered to show a change of at least 7–10%.
AIM To see if adult age correlates with ex vivo protein binding of lorazepam, oxazepam and temazepam in healthy subjects.
METHODS Sixty healthy drug free subjects were recruited in the age groups 18–39, 40–64 and ≥65 years. Plasma albumin concentrations were determined. Ex vivo unbound fractions (fu) were assessed by spiking samples and measuring the free and total concentrations.
RESULTS No correlation of age with fu was seen. The study was powered to demonstrate a change in fu of ≥7–10%. A decline in plasma albumin concentration of ∼0.03 g l−1 year−1 was seen with increasing age (P= 0.032) and was associated with increased fu of lorazepam (P= 0.009) and oxazepam (P= 0.014).
CONCLUSIONS There was no association of adult age with ex vivo fu of lorazepam, oxazepam or temazepam in healthy subjects.