Metoprolol kinetics and dose response in hypertensive patients

Abstract

The kinetics and dose-response characteristics of metoprolol were examined in a series of hypertensive patients. In 14 the elimination half-life of metoprolol after single 100-mg doses (4.1 +/- 0.6 hr) was prolonged (p less than 0.05) after 6 to 12 wk of therapy (5.6 +/- 0.7 hr). In 5 patients receiving 100 mg twice daily evidence of nonlinear metoprolol kinetics emerged, because the area under the concentration-time curve at steady state was 86.8% more (p less than 0.02) than predicted from a single dose. Kinetic data from single doses of metoprolol appear to be a poor predictor of steady-state kinetics. Single metoprolol dosage also induced a fall (p less than 0.01) in blood pressure with pretreatment levels (163/108), reaching a minimum at 5 hr (133/189). During long-term therapy incremented doses of metoprolol between 100 and 600 mg/day in 34 hypertensive patients resulted in a relatively horizontal dose-response curve at doses above 200 mg/day.

A dose ranging study of atenolol in hypertension: fall in blood pressure and plasma renin activity, beta‐blockade and steady‐state pharmacokinetics.

“…The present study confirms previous studies demonstrating, in general, no clear-cut dose-anti- hypertensive response relationship of 8-adrenoceptor blockers in patients with mild-to-moderate hypertension (Douglas-Jones & Cruickshank, 1976;DouglasJones et al, 1978;Marshall et al, 1977Marshall et al, , 1979Myers et al, 1976;Myers & Thiessen, 1980;Serlin etal., 1980) and extends these observations by documenting that the plasma concentration of a f8-adrenoceptor blocker such as atenolol is not a reliable predictor of the hypotensive effect. This seems to be consistent with previous studies where even if a significant correlation between plasma levels of several f3-adrenoceptor blockers and fall in some of blood pressures was found, it was of a weak order or equivocal (Anavekar et al, 1975;Collste et al, 1976).…”

“…There would be the risk of mistake, such that the false conclusion is drawn that no difference exists, when in fact it does (type II error, 8) (Feinstein, 1975;Freiman et al, 1978). Unfortunately, many studies in which the relationship between dose and antihypertensive effect of f3-adrenoceptor blocking drugs including atenolol was examined and negative (no significant differences between dose) conclusions were drawn (Douglas-Jones & Cruickshank, 1976;Douglas-Jones et al, 1978;Jeffers et al, 1977;Marshall et al, 1979;Myers et al, 1976;Myers & Thiessen, 1980;Petrie et al, 1977;Serlin et al, 1980) have not shown ,8-error or the power. This may be largely due to the fact that most studies included too few patients to provide reasonable assurance that a meaningful difference would not be missed.…”

Patient-Specific Effects of Medication Using Latent Force Models with Gaussian Processes

“…, M i → T to map the index of the treatment to a treatment set T representing the type of treatment. Since the dosage-response curve of the same drug usually has a nonlinear curve that varies across dosages (Myers and Thiessen, 1980;Ghassemi et al, 2014), and the characteristics of absorption vary across different routes, we treat the same drug with different dosages or taken via different routes (e.g., oral or injection) as different treatments. Whenever clear from the context, we drop the patient index from these variables.…”

Pharmacokinetic-pharmacodynamic (PK-PD) modeling of cardiovascular effects of metoprolol in spontaneously hypertensive rats: a microdialysis study

“…A poor concentration-response relationship with regard to the hypotensive effect of metoprolol has been found in some studies (von Bahr et al 1976;Myers and Thiessen 1980;Sklar et al 1982), but not in others (Leonetti et al 1975;Esler et al 1977). The suggestion that there is no relationship between plasma levels of antihypertensive drugs and its effect on blood pressure reflects an inadequacy or failure in the approaches designed to detect such correlation.…”