Preliminary evaluation of pinacidil in hypertension.

We have tested the efficacy of a new long‐acting preparation of pinacidil, an arterial vasodilator, using continuous intra‐arterial ambulatory blood pressure recording. An acute dose produced a measurable effect lasting for 12 h. The duration of this effect was less during chronic twice daily drug administration. Side effects were common, causing two out of nine patients to withdraw from the study. Tilt testing produced no postural hypotension and there was no evidence of rebound hypertension on the withdrawal day.

Section: Discussionsupporting

confidence: 83%

“…A single-blind study of the effects of pinacidil in hypertension revealed There were two 48 h periods of intra-arterial BP typical vasodilator side effects whilst the BP recording, separated by 4 to 6 weeks' dose titrareduction lasted less than 6 h (Ramsay & tion of pinacidil. During the first 24 h the patients Freestone, 1983).…”

Section: Introductionmentioning

confidence: 99%

The effects of long‐acting pinacidil on intra‐arterial blood pressure.

Caruana¹,

Al-Khawaja²,

Royston³

et al. 1985

“…Carlsen et al (1981) reported pinacidil to be remarkably free from side effects. In a four patient trial in which pinacidil in the present tablet formulation was added to bendrofluazide with atenolol (Ramsay & Freestone, 1983) three patients had adverse effects whilst taking 20 mg twice daily, and one whilst taking 30 mg twice daily. The same authors reported that after 10 mg of pinacidil a hypotensive effect was detectable at 4 but not at 6 h, and questioned the usefulness of twice daily dosing.…”

Section: Resultsmentioning

confidence: 90%

“…It augmented the hypotensive effect of hydrochlorothiazide (Muiesan et al, 1983), and was effective and well tolerated alone in a 4 week open trial (Carlsen et al, 1983). A placebo controlled trial, with pinacidil as third agent to diuretic and ,-adrenoceptor blocker, was abandoned however because of adverse effects (Ramsay & Freestone, 1983 Figure 1. Doses above 20 mg daily increased mean pulse rate, but only significantly at 7 and 9 weeks in the erect position (P < 0.05).…”

Section: Introductionmentioning

confidence: 99%

Pinacidil monotherapy for hypertension.

Ward¹

1984

Ten patients with mild to moderate hypertension were treated for 9 weeks with a tablet formulation of pinacidil. Mean supine blood pressure fell from 174/100 to 148/84 mm Hg and mean supine pulse increased by 3 beats/min. Daily dosage was 40‐100 mg, given in two or three divided doses. Plasma urea increased significantly and mean weight increased by 1.1 kg. Side effects were frequent but mild, in the main being those typically associated with potent vasodilator drugs. No patient withdrew from the study, and all achieved target blood pressure.

“…Pinacidil is a potassium channel opener which has been shown to be an effective antihypertensive drug in man (Kardel et al, 1981;Ramsay & Freestone, 1983). This is due to the drug's potent vasodilating properties.…”

Section: Discussionmentioning

confidence: 99%

Arterial vasodilating profile and biological effects of pinacidil in healthy volunteers.

Thuillez

Pussard

Richer

et al. 1991

1 The effects of pinacidil (25 mg, sustained release formulation) a) on systemic (arterial pressure, cardiac output) and regional (brachial and carotid arteries' diameters and flows) haemodynamics (pulsed Doppler techniques), b) on sympathetic (plasma noradrenaline) and renin-angiotensin (plasma renin activity) systems, and c) on atrial natriuretic factor have been investigated and compared with those of a placebo during the 12 h period following oral administration in a randomized, double-blind and crossover study performed in six healthy volunteers. Simultaneously, the plasma levels of pinacidil and of its active metabolite, pinacidil N-oxide, were determined. 2 As compared with placebo, pinacidil decreased systemic vascular resistance and arterial blood pressure but cardiac output was not modified. 3 Pinacidil significantly increased brachial and carotid arteries' diameters (by 7 and 8% respectively) and flows (by 60 and 17% respectively) and decreased forearm vascular resistance (by 43%). Thus, pinacidil dilates both large and small arteries, increases large vessels' compliance and redistributes blood flow towards the muscular vascular bed. These effects peaked at 4 h and their duration at the brachial level was 8 h. 4 Pinacidil administration resulted in a stimulation of both sympathetic (increases in heart rate and plasma noradrenaline) and renin-angiotensin systems, and induced a transient increase in atrial natriuretic factor. 5 The duration of pinacidil haemodynamic effects at the brachial level is consistent with the pharmacokinetic data which show that pinacidil and pinacidil N-oxide plasma levels almost plateaued between 3 and 8, and 2 and 8 h respectively after oral administration of the sustained release formulation used.