1 The pharmacokinetics of theophylline and aminophylline was compared after oral administration and intravenous infusion. 2 Theophylline (250 mg) and aminophylline (390 mg) were taken orally by eight healthy volunteers in a randomized cross‐over study. 3 In another cross‐over study theophylline and aminophylline were administered intravenously to six healthy volunteers at a dose corresponding to 5 mg/kg pure theophylline. 4 The protein binding of the theophylline in serum collected during the intravenous study was studied by ultrafiltration. The serum concentration of theophylline was measured by high pressure liquid chromatography. 5 Almost identical concentration‐time curves were found for theophylline and aminophylline in both of the studies. No significant difference was found in the pharmacokinetic parameters or protein binding with the two preparations.

I Fifteen men with untreated essential hypertension in WHO stage 1 were studied on an outpatient basis to evaluate the haemodynamic long-term effect of a new a-and P-adrenergic receptor blocker, labetalol.2 Oxygen consumption, heart rate, cardiac output (Cardiogreen) and intraarterial brachial pressure were recorded at rest in a supine and sitting position, and during steady state work at 300, 600 and 900 kpm/min. 3 The subjects were treated with labetalol (dose 200-800 mg/day) as the sole drug for 1 year. The haemodynamic study was then repeated and the concentration of labetalol in plasma 2-2.5 h after the morning dose was measured. 4 Mean arterial blood pressure was reduced approximately 23% at rest and 21% during exercise. The heart rate was decreased 15% at rest and 16% during exercise. There was a compensatory increase in the stroke volume and consequently the cardiac index was reduced less than the heart rate, 7% at rest supine and 10% during exercise. There was a significant decrease in total peripheral resistance at rest supine (16%) and during exercise (12%). 5 No serious side-effects were seen, but two subjects almost syncopated in the sitting position after the 900 kpm/min work load at the restudy. 6 There was no correlation between the plasma concentration and the effect of labetalol. 7 The haemodynamic changes differ from those seen after long-term therapy with drugs possessing only ,-adrenoceptor blocking properties, and agree well with what should be expected with a drug which possesses both a-and ,-adrenoceptor blocking properties.

I The plasma concentration profile of disopyramide was examined in 13 patients with arrhythmias following acute myocardial infarction.2 Intravenous loading doses of 1.5 mg/kg followed by 0.7 mg/kg and then infusion of 0.3 mg kg-lh-1 resulted in final concentrations between 2.4 and 4.9 mgA1.3 Change-over to oral therapy with disopyramide sustained release (SR) tablets was smooth, and therapeutic plasma concentrations were maintained throughout. 4 Comparison of the plasma concentrations in a subsequent cross-over study with disopyramide plain capsules 150 mg every 6 h and SR tablets 250 mg every 12 h, each being administered for 3 days to attain a steady state, showed that the bioavailability and the variation of the plasma concentration were similar with both regimens. 5 In patients with body weight between 62 and 92 kg disopyramide SR tablets 250 mg every 12 h matched the preceding infusion rate of 0.3 mg kg-'h-I resulting in plasma concentrations close to steady state already on the first day of oral therapy. 6 The absorption of disopyramide SR tablets is only moderately delayed, and the preparation can be used twice daily in direct succession of intravenous infusion.