(6 to 60%) at all doses tested (5 to 80 mg). Lisinopril absorption is not affected by the presence of food in the gastrointestinal tract. Studies in rats indicate that lisinopril crosses the blood-brain barrier poorly. Multiple doses of lisinopril in rats do not result in accumulation in any tissues. Usual bioavailability of ~25% (reduced to 16% in people with New York Heart Association Functional Classification (NYHA) Class II–IV heart failure). Its time to peak concentration is 7 hours. The peak effect of lisinopril is about 4 to 8 hours after administration. Food does not affect its absorption. Distribution Lisinopril does not bind to proteins in the blood. It does not distribute as well in people with NYHA Class II–IV heart failure. Metabolism Lisinopril is the only water-soluble member of the ACE inhibitor class, with no metabolism by the liver. Elimination Lisinopril leaves the body completely unchanged in the urine. The half-life of lisinopril is 12 hours, and is increased in people with kidney problems. While the plasma half-life of lisinopril has been estimated between 12 and 13 hours, the elimination half-life is much longer, at around 30 hours. The full duration of action is between 24 and 30 hours. Chemistry Pure lisinopril powder is white to off white in color. Lisinopril is soluble in water (approximately 13 mg/L at room temperature), less soluble in methanol, and virtually insoluble in ethanol. History Captopril, the first ACE inhibitor, is a functional and structural analog of a peptide derived from the venom of the jararaca, a Brazilian pit viper (Bothrops jararaca). Enalapril is a derivative, designed by scientists at Merck to overcome the rash and bad taste caused by captopril. Enalapril is actually a prodrug; the active metabolite is enalaprilat. The di-acid metabolite of enalapril, enalaprilat, and its lysine analogue lisinopril are potent inhibitors of angiotensin converting enzyme (ACE); they do not contain sulphydryl groups. Both drugs can be assayed by high pressure liquid chromatography and by radioimmunoassay and plasma ACE inhibition remains stable under normal storage conditions. It is therefore possible to study their pharmacokinetics as well as their pharmacodynamic effects in humans. Enalaprilat and lisinopril as well as ACE activity have been measured in blood taken during the course of two studies of the effects of these drugs on blood pressure and autonomic responsiveness. Lisinopril is a synthetic peptide derivative of captopril. Scientists at Merck created lisinopril by systematically altering