The pharmacokinetics of lisinopril was studied after administration of single and multiple doses of 5 mg to hypertensive patients with normal and impaired renal function. In patients with severe renal failure the peak concentrations were higher, the decline in serum concentration was slower and the time to peak concentration was extended. Accumulation of lisinopril was highly correlated with the creatinine clearance. The effective half-life was doubled and tripled in patients with mild and severe renal impairment, respectively, as compared to patients with a normal renal function. Lisinopril lowered blood pressure in all three groups over 24 h. It is suggested that smaller doses of lisinopril should be administered to patients with severe renal failure.

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Milrinone and sulmazole, two recently developed drugs, inhibit specific fractions of the phosphodiesterase (PDE) isozyme system. Since theophylline aspecifically inhibits the PDE complex, we compared the effects of milrinone and sulmazole with those of theophylline on antigen-induced bronchoconstriction, vasoconstriction, mediator release and leukotriene production. In the isolated perfused and ventilated lung of actively sensitized rats, we elicited antigen-induced bronchoconstriction, vasoconstriction and release of mediators like histamine, 5-hydroxytryptamine (5-HT) and slow-reacting substance of anaphylaxis (SRS-A). Milrinone, sulmazole and theophylline inhibited antigen-induced bronchoconstriction and vasoconstriction in a dose-dependent manner with minor differences in potency. Antigen-induced release of preformed mediators like histamine and 5-HT was inhibited only at high concentrations of milrinone, whereas sulmazole failed to inhibit mediator release. Theophylline also failed to inhibit 5-HT release. However, SRS-A synthesis was markedly reduced by these drugs in relatively low concentrations. It is concluded that milrinone and sulmazole have anti-allergic effects similar to those of theophylline and that all three PDE inhibitors reduce SRS-A synthesis.

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