Use this URL to cite or link to this record in EThOS:
Title: Pharmacokinetics of some β-adrenoceptor antagonists : influence of age and altered plasma protein binding
Author: Rigby, James Walter
ISNI:       0000 0001 3518 5832
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 1983
Availability of Full Text:
Access from EThOS:
Full text unavailable from EThOS. Please try the link below.
Access from Institution:
In this thesis two points have been investigated: (1) a comparison of the phamacokinetics of four beta-adrenoceptor antagonists - propranolol, oxprenolol, metoprolol and atenolol - in young and elderly subjects (2) the effect of either decreased albumin or increased alpha1AGP concentration on the elimination of propranolol using the isolated perfused rat liver. Following chronic-oral administration to young and elderly subjects the raised blood concentrations of the four beta - adrenoceptor antagonists were higher in the elderly compared with the young. No significant differences in plasm protein binding were observed, the raised blood concentrations in the elderly were assumed to be due to changes in hepatic metabolism or renal clearance. The calculated total clearance values were lower in the elderly but only for atenolol was the decrease statistically significant. This result was attributed to the larger variability in individual pharmacokinetic parameter values for drugs eliminated by hepatic metabolism compared with renal excretion. The apparent oral clearance and renal clearance of atenolol was positively, correlated with the creatinine clearance. It is suggested that it may be preferable to use those drugs which are predominantly excreted via the renal route in the elderly. The characteristic binding of propranolol to bovine serum albumin and alpha 1-acid glycoprotein was determined by equilibrium dialysis. Propranolol binding to albumin was best described by Concentration-independent partitioning. The binding to alpha1-acid glycoprotein was saturable with two groups of binding sites, one being a high-affinity/low capacity group and the other a low affinity group with higher capacity. aUsing the isolated perfused rat liver, the elimination of propranolol was dependent on perfusate binding. Although binding was dependent on the concentration of both albumin and alpha1AGP in the perfusate, binding to alpha1AGP was more important in determining the extraction ratio of propranolol. The results also suggested that the effect of altered binding was dependent on the route of administration. The route of administration was also important in determining the area under the free propranolol perfusate concentration time curve. After both intravenous and portal administration the area under the free propranolol perfusate concentration-time curve altered as predicted with changes in the free fraction. However, when the alpha1AGP concentration was increased the AUC(free), also increased after portal administration.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Pharmacology & pharmacy & pharmaceutical chemistry