Drugs online research references
J Cardiovasc Pharmacol. 1996 Sep;28(3):470-8.
Pharmacokinetic-pharmacodynamic model relating lisinopril plasma concentrations to regional hemodynamic effects in healthy volunteers.
Bellissant E, Nguyen PC, Giudicelli JF.
Service de Pharmacologie Clinique, Centre Hospitalier de Bicetre, France.
In a previous placebo-controlled, randomized, double-blind, cross-over study performed in 6 healthy volunteers, we investigated the pharmacokinetics and pharmacodynamics of a single oral administration of two doses (5 and 20 mg) of the angiotensin-converting enzyme inhibitor (ACEI), lisinopril. The purpose of the present study was to investigate the relation between lisinopril plasma concentrations (C, ng/ml), and lisinopril-induced effects on plasma converting enzyme activity (PCEA, nmol/ml/min), brachial artery flow (BAF, ml/min), and brachial vascular resistance (BVR, mm Hg . s/ml). PCEA and BVR were expressed in percent changes from initial values and BAF was expressed in absolute values. Effects (E) were related to C by the Hill model: E = Emax . C gamma/CE50 gamma + C gamma). For PCEA, the model was fitted to the data of both doses simultaneously. Emax was fixed at -100%, and we obtained (mean +/- SD) CE50 = 1.4 +/- 0.6 ng/ml and gamma = 0.6 +/- 0.1. For BAF and BVR, the model was fitted to the data of the 20-mg dose for 5 subjects and to those of the 5-mg dose for 1 subject. We obtained Emax = 45 +/- 20 ml/min, CE50 = 24.0 +/- 12.4 ng/ml, and gamma = 3.2 +/- 1.3 for BAF, and Emax = -45 +/- 15%, CE50 = 22.0 +/- 10.2 ng/ml, and gamma = 3.1 +/- 1.1 for BVR. Therefore, the concentration-effect relations for BVR (or BAF) and PCEA display quite different shapes (CE50, gamma), which emphasizes the necessity of performing pharmacokinetic-pharmacodynamic (PK-PD) modeling on hemodynamic parameters to determine the optimal dosages of ACEIs.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8877596&dopt=Abstract
word match zestril online literature
J Am Soc Nephrol. 1996 Oct;7(10):2119-29.
Lifelong angiotensin-converting enzyme inhibition, pressure natriuresis, and renin-angiotensin system gene expression in transgenic (mRen-2)27 rats.
Lippoldt A, Gross V, Bohlender J, Ganten U, Luft FC.
Max Delbruck Center for Molecular Medicine, Virchow Klinikum, Humboldt University of Berlin, Germany.
The transgenic rat (TGR) (mRen-2)27 is said to have low circulating active renin values in plasma and little or no renin gene expression in the kidney. Nevertheless, intrarenal angiotensin II-related effects appear to be responsible for the rightward shift in pressure-natriuresis curves of TGR. To clarify the role of the intrarenal renin-angiotensin system in modulating TGR pressure-natriuresis, TGR were given lifelong lisinopril by treating TGR and their mothers before conception. Rat and mouse renin, AT1 receptor, and angiotensinogen gene expression in the kidneys were studied with in situ hybridization. Neural and endocrine regulatory differences between TGR and Sprague-Dawley Hannover (SDH) rats were eliminated by renal denervation and infusion of vasopressin, aldosterone, 17-OH corticosterone, and norepinephrine. TGR with lisinopril had blood pressures similar to SDH. In TGR with lisinopril, the pressure-natriuresis curve was shifted leftward but not quite to the values observed in SDH given lisinopril. The histology of lisinopril-treated TGR was indistinguishable from normal SDH. Lisinopril increased rat renin and angiotensinogen gene expression both in SDH and TGR, but it did not influence mouse renin gene expression in TGR. Discontinuing lisinopril increased blood pressure in TGR and shifted the pressure-natriuresis relationship rightward. Thus, the components of the endogenous renin-angiotensin system and the mouse renin transgene were present and expressed in kidneys of TGR. The rat gene components responded to lisinopril as expected, but the mouse renin transgene expression was not influenced. Lisinopril normalized TGR blood pressure; however, a detectable leftward shift in pressure-natriuresis remained. These studies underscore the role of angiotensin-mediated effects of the mouse renin transgene in terms of shifting pressure-natriuresis in TGR.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8915971&dopt=Abstract
word match zestril online literature
Br J Pharmacol. 1996 Nov;119(5):943-8.
Renal effects of concurrent E-24.11 and ACE inhibition in the aorto-venocaval fistula rat.
Kirk JE, Wilkins MR.
Department of Clinical Pharmacology, Royal Postgraduate Medical School, London.
1. The present studies compare the early renal response to (a) an endopeptidase-24.11 (E-24.11) inhibitor (candoxatrilat) (b) an angiotensin-converting enzyme (ACE) inhibitor (lisinopril) and (c) the combination of endopeptidase-24.11 and ACE inhibition in the rat A-V fistula model of chronic volume overload. 2. Candoxatrilat (3 and 10 mg kg-1) i.v. produced a prompt 3 fold increase in urinary sodium and cyclic GMP excretion without affecting significantly blood pressure or glomerular filtration rate (GFR). 3. Lisinopril (0.03 mg kg-1) alone inhibited the pressor response to angiotensin I but had no significant effect on urinary sodium excretion or blood pressure. 4. Lisinopril (0.03 mg kg-1) attenuated significantly the early natriuretic response to candoxatrilat (3 mg kg-1) and the associated rise in urinary cyclic GMP, but sodium excretion eventually reached levels associated with acute E-24.11 inhibition. 5. Doses of the dual E-24.11/ACE inhibitor, sampatrilat, that inhibited the pressor response to angiotensin I reduced mean arterial blood pressure and produced a delayed natriuresis and rise in urinary cyclic GMP excretion when compared to candoxatrilat alone. 6. Concurrent administration of an ACE inhibitor reduces the early renal response to E-24.11 inhibition in the A-V fistula rat, an effect attributable to the hypotensive action of this combination.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8922744&dopt=Abstract
word match zestril online literature
Herbs and Pharmaceuticals Online ||
Hair Million herbal formula for hair loss and hair growth ||
Antibiotics and prescription medications online literature ||