Studies on the pharmacokinetics and pharmacodynamics of atenolol in man

Abstract

The non-stimulant cardioselective beta adrenocepter antagonist atenolol has been studied in volunteers in order to define its pharmacokinetic characteristics. Atenolol (100 and 200 mg orally) is rapidly absorbed, reductions in heart rate and systolic pressure being observed in 30 min. The effect persists for up to 8 h. Over 85% of an intravenous dose is excreted in urine within 24 h but only 50% of an oral dose. The bioavailability of approximately 50% is due to reduced absorption. Peak blood levels are observed at 2-4 h and the half life of atenolol given orally is 5-6 h. Atenolol reduces the cardiac response to standing and head-up tilt. It does not reduce circulating levels of renin but slightly impairs the renin response to tilt. Atenolol both orally and intravenously reduces supine diastolic pressure about four hours after administration, the effect persisting for up to 24 h.

Pharmacokinetics of atenolol in patients with terminal renal failure and influence of haemodialysis.

“…Nevertheless, the calculated AUC (plasma concentration against time) gave a value of 129.2+54.6 mg h 1-', which is higher than that (Flouvat et al, 1978) and 13.45 mg h I( Fitzgerald et al, 1978) for the same dose (200 mg). The mean plasma levels 1.12 + 0.37 mg/I, observed 24 h after dose administration, account for the increase in AUC ( oo ).…”

“…The mean apparent plasma half-life value was 51.2+ 17.3 h (n=6). This value is significantly higher than during dialysis (P < 0.001) ( (Fitzgerald et al, 1978;Flouvat et al, 1978). This delay in the appearance of plasma peak was observed by Kaye, Kumana, Franklin & Baker (1975) for practolol, by Thompson, Joekes & Foulkes (1972) (Flouvat et al, 1978) (1.04+0.19 mg/I).…”

“…The mean plasma levels 1.12 + 0.37 mg/I, observed 24 h after dose administration, account for the increase in AUC ( oo ). In normal subjects this value is only about 0.2 mg/l (Fitzgerald et al, 1978;Flouvat et al, (1978). Sassard, Pozet, McAinsh, Legheand & Zech (1977) in patients with severe renal insufficiency (inulin clearance 16 + 4 ml min 11.73 m -2) 24 h after a 100 mg oral dose, found plasma levels of about 0.4 mg/l.…”

“…Their patients maintained a relative whole body clearance of atenolol (38 + 10 ml min-' 1.73 m-2); in our patients, atenolol renal clearance is very low (4.6 + 1.5 ml/min) and in good agreement with creatinine clearance. These values can be compared because atenolol is almost entirely renally excreted (Fitzgerald et al, 1978;Flouvat et al, 1978), and predominantly in the unchanged form (Reeves, McAinsh, McIntosh & Winrow, 1978 (Eastwood, Curtis & Smith, 1973). During haemodialysis, the mean apparent plasma half-life of atenolol (7.5 h) is significantly lower (P<0.001) than the average value after dialysis (51.2 h) and in patients not yet dialysed (73.4 h).…”

“…Since atenolol is a drug almost entirely renally excreted (Fitzgerald, Ruffin, Smedstad, Roberts & McAinsh, 1978;Flouvat, Bazin, Lucsko, Roux & Guedon, 1978), the object of the present work was to study the pharmacokinetics of atenolol in patients 0306-5251/80/040379-07 $01.00 undergoing regular dialysis treatment and the effects of dialysis on these pharmacokinetics.…”