Drugs online research references
Br J Pharmacol. 1993 Jul;109(3):873-9.
Effects of lisinopril on electromechanical properties and membrane currents in guinea-pig cardiac preparations.
Valenzuela C, Perez O, Casis O, Duarte J, Perez-Vizcaino F, Delpon E, Tamargo J.
Department of Pharmacology, School of Medicine, Universidad Complutense, Madrid, Spain.
1. The effects of the angiotensin-converting enzyme inhibitor, lisinopril, were studied in guinea-pig atria and papillary muscles and in single isolated ventricular cells. 2. In isolated right atria, lisinopril (0.001-10 microM) decreased the amplitude and rate of the spontaneous contractions. In electrically driven left atria this negative inotropic effect was accompanied by a shortening of the time to peak tension and time for total contraction. 3. Lisinopril did not modify the electrophysiological characteristics of the ventricular action potentials recorded in papillary muscles perfused with normal Tyrode solution or elicited by isoprenaline in papillary muscles perfused with 27 mM K Tyrode solution. 4. In single ventricular cells, lisinopril (10 microM) had no effect on the inward L-type Ca2+ (ICa,L), the inward rectifier (IK1) or the delayed rectifier K+ currents (IK). However, it abolished the stimulation-dependent facilitation of the L-type Ca2+ current. 6. These results indicate that the negative inotropic effect of lisinopril cannot be explained by a decrease in Ca2+ entry through L-type channels and suggest that lisinopril may possibly act at an intracellular site to reduce contractile force.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7689408&dopt=Abstract
Br J Pharmacol. 1990 May;100(1):90-4.
Preferential biliary elimination of FPL 63547, a novel inhibitor of angiotensin-converting enzyme, in the rat.
Carr RD, Cooper AE, Hutchinson R, Mann J, O'Connor SE, Robinson DH, Wells E.
Department of Pharmacology, Fisons plc, Research and Development Laboratories, Loughborough, Leics.
1. The route of elimination of FPL 63547, a novel inhibitor of angiotensin-converting enzyme (ACE), has been investigated in the anaesthetized rat. Comparisons have been made with other ACE inhibitors. 2. Bile and urine samples were collected over a 5 hour period following a single i.v. dose of ACE inhibitor (2 mumol kg-1). Samples were bioassayed for ACE inhibitory activity using affinity-purified rabbit lung ACE and the amounts of the active form of inhibitor present in each sample were calculated by comparison with a standard curve. 3. FPL 63547 was rapidly and extensively excreted as the diacid in the bile but appeared in the urine in negligible amounts. The bile:urine ratio was 21.4:1 indicating a marked preference for the biliary route. A similar elimination profile was observed when the compound was dosed in its active form (FPL 63547 diacid), 87.9% of which was found in the bile over the 5 h collection period, with a bile: urine ratio of 14.6:1. 4. The marked preference of FPL 63547 for biliary elimination was not shared by the other ACE inhibitors tested in this study. Lisinopril demonstrated the opposite pattern, being excreted almost exclusively by the kidney (bile:urine ratio 0.06:1). Enalapril was eliminated in approximately equal amounts in bile and urine (ratio 0.7:1) while spirapril diacid showed a slight preference for the bile (ratio 2.6:1). 5. The physical chemical properties of FPL 63547 diacid may be responsible for its unusual preference for biliary elimination. In particular, the amphipathic character and strong acid functionality of the compound are thought to favour transport into the bile.(ABSTRACT TRUNCATED AT 250 WORDS)
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2164864&dopt=Abstract
J Hum Hypertens. 1989 Jun;3 Suppl 1:153-8.
Pharmacokinetics of enalapril and lisinopril in subjects with normal and impaired hepatic function.
Hayes PC, Plevris JN, Bouchier IA.
Department of Medicine, Royal Infirmary, Edinburgh, Scotland.
The pharmacokinetic and pharmacodynamic profiles of two angiotensin-converting enzyme (ACE) inhibitors, enalapril (a prodrug) and lisinopril (directly acting), were compared in eight patients with hepatic cirrhosis and 10 healthy controls. The pharmacokinetics of both drugs were affected in patients with hepatic cirrhosis. The percentage urinary recovery of the parent (inactive) drug enalapril was higher in patients with cirrhosis than controls. Serum concentrations of both drugs showed considerable variation in cirrhotic patients, but the variance ratio between patients with cirrhosis and controls was greater for enalapril than lisinopril. Peak serum concentrations of both ACE inhibitors were higher in patients with cirrhosis than in controls, which may be due to increased drug absorption. The time to peak drug concentration was longer for lisinopril than enalapril.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2550638&dopt=Abstract
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