1 The effects of single doses of doxazosin, a quinazoline derivative similar to prazosin, were studied in six normotensive volunteers. 2 Both 1 mg (i.v.) or 2 mg (oral) doxazosin caused a fall in blood pressure which was most apparent in the erect posture at 5-6 h following drug administration. The maximum fall in blood pressure following i.v. doxazosin was from 123/81 to 106/69 mm Hg associated with a rise in heart rate from 81 to 107 beats/min. 3 The terminal elimination half-life following oral and intravenous doxazosin was about 9 h.4 Pressor responsiveness to the a, -adrenoceptor agonist, phenylephrine, showed no significant difference between oral and i.v. doxazosin suggesting that the route of administration did not influence a, -adrenoceptor antagonism at the doses used.5 Using a pharmacodynamic modelling technique in individual subjects, there was a significant correlation between the change in doxazosin concentration in the effect compartment and its hypotensive effect. 6 With the modelling technique it was possible to show a significant correlation between the pressor responsiveness to the a, -adrenoceptor agonist phenylephrine and the concentration of doxazosin in the effect compartment. This is consistent with the concept that the hypotensive effect of doxazosin is mediated by a,-adrenoceptor blockade.

The bioavailability of carbazeran and the metabolism of carbon-14 labelled drug have been studied in the dog and man following oral administration. The drug was moderately well absorbed in both species, but there was a marked difference in bioavailability and in routes of metabolism. In the dog, systemic bioavailability was approx. 68% and biotransformation involved mainly O-demethylation. In man, bioavailability was not measurable and carbazeran was almost completely cleared via 4-hydroxylation of the phthalazine moiety. Thus the lack of detectable pharmacological effect in man following oral administration of the drug appears to be due to presystemic metabolism by a particularly active pathway not found in the dog.

1 Doxazosin is a quinazoline derivative, related to prazosin, recently developed for the treatment of hypertension. 2 The intravenous administration of doxazosin (12 micrograms/kg) to six healthy normotensive subjects resulted in significant fall in erect blood pressure, with a corresponding increase in heart rate, but there were no significant changes in supine blood pressure or heart rate. 3 The changes in blood pressure and heart rate were maximal at 6 h after intravenous dosing. With prazosin the maximum effects occurred within the first hours. 4 Pressor response studies with phenylephrine confirmed that doxazosin is a relatively selective postsynaptic alpha‐ adrenoceptor antagonist. 5 The mean elimination half‐life of doxazosin was 11 h. This compared with a T1/2 of 2.5 h for prazosin.

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Residual beta cell function was studied in 18 juvenile-onset diabetics by measuring serum C-peptide immunoreactivity (CPR) fasting, and after IV injection of glucagon (1 mg). This was compared with the exocrine pancreatic response to an IV infusion of secretin and cholecystokinin-pancreozymin. Outputs of pancreatic bicarbonate, amylase and trypsin were measured. Exocrine secretory pancreatic function was decreased in 14 patients. Fasting and maximal CPR showed that 9 patients had residual insulin secretion. For these 'CPR-secretors' there was a strong correlation between CPR and output of bicarbonate (r = 0.87, p less than 0.005) and amylase (r = 0.7, p less than 0.05), but not with trypsin. These results suggest the existence of an endocrine-exocrine relationship in the pancreas.