Drugs online research references
J Vet Intern Med. 1998 Mar-Apr;12(2):93-5.
Comparison of some pharmacokinetic parameters of 5 angiotensin-converting enzyme inhibitors in normal beagles.
Hamlin RL, Nakayama T.
Department of Veterinary Biosciences, College of Veterinary Medicine, Ohio State University, Columbus 43210-1092, USA.
This study was designed to determine the degree of inhibition of the angiotensin-converting enzyme (ACE) in 5 normal dogs given single doses of conventionally used ACE inhibitors (ACEis). In addition the time required for that inhibition to return to 50% of the difference between maximum and zero (control values) was measured as an estimate of duration of action. The 5 ACEis (with dosages given in parentheses) were benazapril (0.5 mg/kg), captopril (2.0 mg/kg), enalapril (0.5 mg/kg), lisinopril (0.5 mg/kg), and ramipril (0.25 mg/kg). Blood samples for ACE activities were obtained before dosing and at 1.5, 3.0, 6.0, 12.0, and 24.0 hours after dosing. All ACEis except captopril decreased ACE activities to approximately 25% of control by the 1.5- to 3.0-hour sample, and ACE activities returned to 50% of the difference by the 12-hour sample. The value of AVE activity returned to normal by 24 hours for benazapril, whereas values for ACE activity remained below normal for enalapril, lisinopril, and ramipril at 24 hours. For captopril, however, ACE levels decreased to approximately 80% of control by the 1.5-hour recording, and returned to levels not different from control by the 3-hour recording. Based upon this study performed on normal dogs given a single dose, no pharmacokinetic advantage or disadvantage is apparent for any ACEi except captopril, which, at the dosage used, decreased ACE levels to a much lesser degree and shorter time.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9560765&dopt=Abstract
Am J Cardiol. 1987 Apr 24;59(10):3D-11D.
Ramipril: review of pharmacology.
Becker RA, Scholkens B.
Ramipril is a potent orally active converting enzyme inhibitor. Its active metabolite ramiprilat is classified as a reversible, slow- and tight-binding inhibitor. Ramipril lowers blood pressure in various models of hypertension and improves states of acute cardiac failure mainly by suppression of angiotensin II formation. Actions on both vasoconstrictor and volume factors are involved because ramipril causes vasodilation and mild natriuresis but preserves potassium. Sustained inhibition of converting enzyme in target tissues such as vascular wall, kidney and heart may explain cardiovascular changes over the long term. Ancillary effects may possibly emerge from modulation of the sympathetic nervous system but the contribution of bradykinin potentiation remains unclear.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3034030&dopt=Abstract
Am J Cardiol. 1987 Apr 24;59(10):65D-69D.
Pharmacokinetics and pharmacodynamics of ramipril in renal failure.
Aurell M, Delin K, Herlitz H, Ljungman S, Witte PU, Irmisch R.
The pharmacokinetics and pharmacodynamics of the novel angiotensin converting enzyme (ACE) inhibitor ramipril were studied in 6 patients with a glomerular filtration rate of less than 20 ml/min/1.73 m2 of body surface area. A single oral dose of 5 mg was given and serum concentrations of the compound and its diacid, the active metabolite (ramiprilat), as well as ACE activity, blood pressure and pulse rate were monitored for 28 days. The original compound reached peak serum concentrations of 42.8 +/- 26.5 ng/ml about 1 hour after dosing and was completely eliminated from the serum after 24 hours. Ramiprilat reached peak values of 14.4 +/- 11.6 ng/ml after about 6 hours. In contrast with the parent compound, low concentrations of ramiprilat were still detected in the serum after 28 days. ACE activity decreased to approximately 5% of baseline values, remained low for the next 48 hours, then increased slowly thereafter but reached only 84.5% of initial values after 28 days. Blood pressure decreased significantly and remained low for 24 hours after dosing. The drug was well tolerated in all patients. It is concluded that a single 5 mg dose of ramipril was effective in inhibiting plasma ACE activity and lowering blood pressure in patients with renal failure. There was a slower decline in ramiprilat concentrations compared with subjects with normal renal function.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3034036&dopt=Abstract
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