Prazosin plasma levels

Figure 12. Plasma Levels of Prazosin Following Injection of PHPG-Prazosin Conjugate Subcutaneously in Rabbits (n=3).

Hepatic 0-dealkylation and glucuronide formation appear to be major pathways of biotransformation. Only about 10% of orally administered prazosin is excreted in the urine. Plasma levels of prazosin are increased in patients with renal failure the nature of this interaction is unknown. 

The plasma levels of both indoramin and alcohol may be raised by concurrent use. The combination of alcohol and indoramin has been reported to increase drowsiness, which may possibly increase the risks when driving or using machinery. Prazosin appears to enhance the hypotensive effects of alcohol. 

Severe hypotension and bradycardia have been seen in patients taking captopril or verapamii when they were given epidurai anaesthesia with bupivacaine. Acute hypotension aiso occurred in a man taking prazosin when he was given epidurai anaesthesia with bupivacaine. Cionidine may increase the duration of caudal block with bupivacaine, aithough there are reports of reduced plasma levels of lidocaine with concurrent cionidine. Verapamil does not appear to interact with epidural lidocaine. 

Wood, A. ., Bolli, P. and Simpson, K O., (1976) Prazosin in normal subjects plasma levels, blood pressure and heart rate. Brit. J. clin. Pharmacol, 3, 199. 

Prazosin is readily absorbed after oral administration, peak serum levels occur approximately 2 hours after a single oral dose, and the antihypertensive effect of prazosin persists for up to 10 hours. Its half-life in plasma ranges from 2.5 to 4 hours, and elimination from plasma appears to follow first-order kinetics. The drug is extensively (perhaps as high as 97%) bound to plasma proteins this observation partially explains the lack of correlation between plasma drug levels and persistence of antihypertensive effect. 

Prazosin may be particularly useful when patients cannot tolerate other types of antihypertensive agents or when blood pressure is not well controlled by other drugs. Since prazosin does not significantly influence blood uric acid or glucose levels, it can be used in hypertensive patients whose condition is complicated by gout or diabetes meUitus. Prazosin treatment is associated with favorable effects on plasma lipids. Thus, it may be of particular importance in managing patients with hyperlipidemia. 

ALPHA-BLOCKERS CARDIAC GLYCOSIDES Possibility of T plasma concentrations of digoxin no cases of toxicity have been reported with doxazosin or prazosin Doxazosin inhibits P-gp-mediated elimination of digoxin mechanism with prazosin is uncertain at present Monitor digoxin levels... 

Antihypertensive Vasodilators - Prazosin (Pfizer) has been introduced - -0 into the U.S. Unlike other vasodilators it causes a decrease in plasma renin levels.79 The use of hydralazine has been reviewed, and the structure-activity relations of hydrazinopyridazines and phthalazines have been studied using molecular orbital calculations8l and Hansch analysis. 2 Animal pharmacology has been summarised and the first clinical data reported83 for Lepetit 6150 (15 ). In 20 patients it was found to be 8 times... 

The already mentioned proteins OCTI and OCT3 transport small cationic substances, such as tetraalkyl ammonium compounds, polyamines such as spermine, monoamino-neurotransmitters, or N-methyl-nicotinamide across the basolateral plasma membrane [56]. OCTs play a key role in the distribution of cationic drugs and, therefore, drug interactions at the transporter level may become clinically relevant, as compounds with high affinity, such as prazosin or phenox-ybenzamine, may affect the excretion of other substrates. Certain liver diseases or obstructive cholestasis may result in alterations of hepatic clearance via these transporters. In rats, a 7-day bile duct ligation resulted in a marked downregulation of Octi and an increased hepatic accumulation of the Octi substrate tetraethylammonium [57]. 

Copur S, Tokgozoglu L, Oto A, Oram E, Ugurlu . Effects of oral prazosin on total plasma digoxin levels. Fundam Clin Pharmacol (1988) 2,13-17. 

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