Indication:
Hypertension
Summary-
Dilevalol, an isomer of labetalol, is a noncardioselective Betadrenergic blocking agent with
significant vasodilatory (Beta agonist) activity, therfore, it may have advantages over other
agents in the class in certain hypertensive patients with altered conduction.
Black patients and patients with renal insufficiency may also benefit. It also appears to be
well tolerated, with minimal side effects reported. It is usually adminstered once daily and can be given orally or IV.
An NDA for the oral form was filed in 1986. InJanuary 1990, the FDAs Cardio- Renal Advisory Committee recommended approval for dilevalol. However, due an increasing incidence of hepatoxicity, the manufacturer decided to withdraw the NDA and discontinue the worldwide marketing of the drug.
Pharmacology/ Pharmacokinetics:
Pharmacology-
Dilevalol , a non selecectiv, betadrenergic blocking agent, is the R-R isomer of the
labetolol ( Normodyne) , Transdalol) , one of the four optimal isomers of the drug.
Althogh dilevalol is virtually devoid of alpha 1- blocking activity, having one-fourth to
one-third the activity of labetalol, it has app 7 times the vasodilatorty effect. However,
this effect appears to be mediated via the beta-2 antagonist effcec as opposed to
alpha1- blocking effect . Dilevalo has app 4 times the beta-blocking effect (B1and B2)
effect of labetol. The degree of beta-receptor blockade appears to be similar ro
propranol ( eg Inderal)
Dilevalol appears to decrease the periheral vascular resistence with no effect on
cardiac output. The refllex increase in heart rate that might be expected with vasodilation
is counteracted bt the drugs beta -blocking activity. In one study 29 patients heart rate
actually decreased by 8 beats per minute as compared to placebo
Pharmacokinetics-
Dilevalo is rapidly absorbed following oral admin. reaching peak levels within 1 hour.
Following absorption, it is rapidly distributed in the extravascular system .In 12 volunteers
the mean maximam concentration was 62ng/ml . Plasma levels appear to increase in a dose related manner.
Metabolism /Excretion- dilevalol undrgoes extensive first-pass metabolism (85% to 95%),
resultin in absolute bioavailability of 11% to 14%. The half-life is app 8 hours following
oral administration, and 12 hours following IV , indicating that dilevilol need only be given
once daily.
The metabolites are conjugated with glucoronides and are excreted in urine. Approximately
3% the drug was excreted unchanged after IV administration in 12 volunteers.
Plasma concentrations do not appear to be altered in severe renal impairment
Clinical trials-
Dilevalol in once daily doses of 100 to 800mg is effective in the treatment of mild to moderate hypertension. Because of its vasodilatory effects, it may be more useful than other agents of this class in hypertensive patients with comparomised myocardial function or peripheral vascular insufficiency.
Since it does not affect the glomerular filtration rate, renal plasma flow, renal blood flow, or
renal vascular resistence it may be in patients with renal insufficiency. Some studies also
indicate a possible benefit in black patients. It is effective when adminstred orally and IV.
In several studies , dilevalol was equal to or greater than labetalo, metoprolol, and atenolol
(Tenormin) in antihypertensive efficacy, with less side effects. In one study comparing
dilevalol with atenolol,patients receiving dilivalol showed greater and longer derease in mean arterial pressure.
Although only reported in two patients, dilevalol may be useful for the treatment of
pheochromocytoma, It may also be useful , administred IV, in the management of severe
hypertension. Further studues are needed
Manufacturer Details