Pharmacokinetics of Prazosin in Normotensive Subjects After Low Oral Doses

Abstract

A method for measuring plasma prazosin concentrations is reported. This method, which involves high pressure liquid chromatography (HPLC) combined with fluorescence detection, has a sensitivity 20 times that of previous conventional fluorimetric techniques and twice that of other HPLC methods, and can be used to study the pharmacokinetics of prazosin at very low doses. Plasma prazosin concentrations were measured in 5 normal volunteers for 24 hours after single oral doses of 0.5 and 1.5mg of prazosin. On average, the lag time was 0.650 and 0.448 hours, and the elimination half-life 2.3 and 2.5 hours, for the 0.5 and 1.5mg doses, respectively. Peak prazosin concentrations occurred between 1.1 and 3.6 hours after dosing, and after the 1.5mg doses were associated with symptoms of faintness.

The effect of a single oral dose of prazosin on venous reflex response, blood pressure and pulse rate in normal volunteers.

“…Other workers also noted similar reproducibility of the VRR for several hours in normal subjects (Samueloff et al, 1966). Moreover, the timing and symptomatic severity of the orthostatic hypotension exhibited by these healthy subjects (Table 2) appeared to be analogous to that since described following similar and larger doses (up to 5 mg) of prazosin, initially administered to both hypertensive patients (Bendall et al, 1975;Graham et al, 1976), and to normal subjects (Dynon et al, 1980;Rubin & Blaschke, 1980). Although previous studies of hypertensive patients suggested lack of significant tachycardia in association with prazosin therapy (Stokes & Oates, 1978), the observation of significant orthostatic tachycardia in these healthy subjects (Tables 3 and 4) is consistent with the significant prazosin-related orthostatic tachycardia recently reported to have occurred in other normal subjects (Dynon et al, 1980;Rubin & Blaschke, 1980).…”

“…Although the plasma prazosin concentration may not have reached its peak in two of the subjects (2 and 4), who continued to exhibit symptomatic orthostatic hypotension, the onset of the latter effect appeared to coincide with the peak plasma level in two subjects (5 and 6), whereas it preceded the peak in one subject (1) and followed the peak in another (3) Tables 2 and 5). These findings reflect the reported absence of a precise relationship between peak plasma prazosin concentration and the degree of orthostatic hypotension following oral initial and continued administration of the drug (Bateman et al, 1979;Dynon et al, 1980;Graham etal., 1976;MacCarthyetal., 1980;Rubin & Blaschke, 1980). However, the demonstration of a significant relationship between plasma prazosin concentration and hypotensive response after intravenous administration to normal subjects (Bateman et al, 1979) suggests that the pre-systemic modification of the parent compound confounds the cardiovascular mechanisms determining arterial blood pressure.…”

Acute and Chronic Cardiovascular Effects of Indoramin and Prazosin in Normal Man

“…Studies in normal man have shown that after a single oral dose of prazosin or indoramin supine heart rate is unchanged, although prazosin may reduce supine arterial pressure (Bateman et al, 1979;Royds, Col-0306-5251/81/130061-06 $01.00 tart & Lockhart, 1972;Rubin & Blaschke, 1980). In normal and hypertensive man, arterial pressure on standing is reduced by prazosin, and heart rate increased (Bateman et al, 1979;Dynon et al, 1980;Kincaid-Smith et al, 1976;Rubin & Blaschke, 1980). In normal and hypertensive man, arterial pressure on standing is reduced by indoramin; heart rate is unchanged in normal subjects, and reduced in hypertensive patients (Carballo et al, 1974;Faerchtein et al, 1976;Marshall, Kettle & Barritt, 1980;Royds et al, 1972).…”

The influence of food on the oral bioavailability of terazosin [letter]

“…procedure using a fluorescence detector with a prazosin analogue as an internal standard. The method was based on the procedure developed for prazosin (Dynon et al, 1980). The detection limit was 0.25 ng ml-' using 1 ml plasma.…”