Concentration‐effect relationship of oxprenolol in healthy volunteers: a retrospective analysis.

Abstract

1 A mathematical model describing the relationship between plasma concentrations of oxprenolol and submaximal-exercise heart rates has been developed on the basis of data available from 34 healthy volunteers. 2 This relationship, which is exponential in type, is consistent with the 'law of diminishing returns', and is independent of the pharmaceutical formulations used; it appears to be established instantaneously, and is not modified by repeated drug administration over 8 days.3 At oxprenolol concentrations of 190-250 ng/ml, between half and three-quarters of the subjects investigated reached 90% of their estimated maximum levels ofadrenoceptor blockade.

Concentration‐effect relationships for oxprenolol in patients with essential hypertension.

“…Although the plasma oxprenolol concentrations in our hypertensive population were approxi-mately two-fold greater than those in healthy young subjects (Bennett et al, 1985), analysis of the relationship between oxprenolol concentrations and reduction in exercise induced tachycardia gave similar parameter values in the two groups (Racine-Poon & Moppert, 1985). This suggests that sensitivity to oxprenolol does not differ greatly between hypertensives and normals.…”

“…(b) Plasma concentration-effect relationships Plasma oxprenolol concentrations and postexercise heart rates were fitted to the mathematical model of Racine-Poon & Moppert (1985) using a computerised non-linear least-squares regression method, NONLIN (SAS, 1982). The equation defining the relationship is given by:…”

“…reflecting the overall sensitivity of the responses Rmax = the maximum achievable effect and is given by RO-Rmin Data from days 1 and 15 were pooled, since chronic dosing does not appear to modify the dynamic response to oxprenolol (Racine-Poon & Moppert, 1985).…”

“…Hitherto, plasma concentration-effect relationships for EHR and BP have been described mainly in terms of a loglinear model (Brunner et al, 1975;Israili, 1979;McAinsh et al, 1978;McDevitt, 1977;Martin et al, 1978;Mason & Winer, 1976) but this approach has limitations (Holford & Sheiner, 1981), and as it depends on mean results, no allowance is made for variability in responses. The experimental model used here (Racine-Poon & Moppert, 1985) allows the inclusion of additional terms to account for drug and subject attributes and thus represents a more general description of the kinetic-dynamic relationship.…”

CNS‐related performance and haemodynamics of metoprolol‐Oros and propranolol after single and 3 days dosing in healthy volunteers.

“…Changes in resting heart rate have been used in some studies, but these may not accurately reflect ,B-adrenoceptor blockade (McDevitt, 1977). In this study we used submaximal exercise heart rate reduction as an indicator of the level of peripheral P-adrenoceptor blockade (Israili, 1979), as changes in exercise heart rate have been shown to reflect plasma levels of ,-adrenoceptor blockers (McInnes & Brodie, 1988b;Racine Poon & Moppert, 1985) while concentration effect relationships appear to be similar in healthy volunteers and in hypertensive patients (McInnes & Brodie, 1988b). In our study, ,-adrenoceptor blockade increased significantly between the first and third day following metoprolol-Oros.…”