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

Abstract

1 Plasma drug concentrations, and heart rate and blood pressure responses to exercise at a predetermined load were examined in twelve hypertensive patients following single and repeated doses of oxprenolol administered once daily as oral osmotic drug delivery systems (10/170 and 16/260 oxprenolol OROS). 2 Plasma oxprenolol concentration profiles after each preparation were consistent with the criteria for sustained drug release. Levels immediately after exercise were significantly higher than those prior to exercise (P < 0.001), but differences were slight. 3 Both OROS drug forms reduced exercise heart rate for 24 h after single and repeated doses; effects were greater for 16/260 OROS than for 10/170 OROS. Significant reductions in post-exercise systolic BP were observed 24 h after drug administration and after repeated doses there was little difference between the preparations. Effects on diastolic BP after exercise were slight. 4 The relationship between plasma oxprenolol concentrations and exercise heart rates fitted an exponential mathematical model which makes allowance for inter-individual variability. No such kinetic-dynamic relationship could be defined for post-exercise systolic or diastolic BP.

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.…”