Abstract:
:The pharmacokinetics, pharmacodynamics, and safety of fosinopril sodium (SQ 28,555), a new orally active angiotensin-converting enzyme (ACE) inhibitor, was evaluated in 73 healthy men in two separate studies. In study I, doses ranging from 10 to 640 mg were administered once daily for 3 days to seven groups of five subjects each. Serum aldosterone levels, ACE activity, and sitting blood pressure were determined, as were pharmacokinetic parameters of fosinoprilat, the active diacid of fosinopril. In a dose-tolerance study (study II), 80 and 160 mg of the drug were administered in doses of 40 mg bid and 80 mg bid for 2 weeks. Pharmacokinetics were determined on days 1 and 14, and blood pressure and ACE activity were measured daily. One hour after all doses of fosinopril, serum ACE activity was undetectable. Peak blood levels of fosinoprilat occurred at about 3 hours after dosing, and linear kinetics of the diacid were observed. ACE activity remained undetectable for more than 24 hours after the treatment was stopped in study II. Serum aldosterone levels were decreased by 50% of baseline values in both studies. In study I, maximal reductions in mean blood pressure occurred approximately 6 hours postdose; once-daily doses of 20 mg or greater achieved reductions of 11.3 to 21.6% (P less than or equal to .05, compared with placebo reductions). Fosinopril was well tolerated. Subjects reported only mild gastrointestinal complications at doses of 80 mg/day or higher. These data show that fosinopril is a safe and effective inhibitor of ACE with a long duration of action on serum ACE activity.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Duchin KL,Waclawski AP,Tu JI,Manning J,Frantz M,Willard DAdoi
10.1002/j.1552-4604.1991.tb01887.xsubject
Has Abstractpub_date
1991-01-01 00:00:00pages
58-64issue
1eissn
0091-2700issn
1552-4604journal_volume
31pub_type
临床试验,杂志文章abstract::The objective of this study was to determine the absolute oral bioavailability and disposition of omapatrilat. This single-dose, randomized, crossover study of 20 mg intravenous and 50 mg oral [14C]omapatrilat was conducted in 12 healthy male subjects to determine the disposition and oral bioavailability of omapatrila...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1177/00912700122010726
更新日期:2001-08-01 00:00:00
abstract::Although population studies have demonstrated a relationship between casual office blood pressures and target organ events, the variability of these blood pressure measurements for individual patients has generated an interest in the role of ambulatory blood pressure monitoring for defining the presence of hypertensio...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1002/j.1552-4604.1992.tb05771.x
更新日期:1992-07-01 00:00:00
abstract::A pediatric population pharmacokinetic model including covariate effects was developed using data from 2 clinical trials in pediatric patients with epilepsy (SP0847 and SP1047). Lacosamide plasma concentration-time data (n = 402) were available from 79 children with body weights ranging from 6 to 76 kg, and a balanced...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/jcph.1340
更新日期:2019-04-01 00:00:00
abstract::The antihypertensive effect of enalaprilat (MK-422), an intravenous (IV), nonsulfhydryl converting-enzyme inhibitor, was evaluated in a double-blind study of 14 patients with mild to moderate hypertension. The seven patients in the treatment group initially received IV enalaprilat 1.25 mg q6h for 24 hours. Thereafter,...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1002/j.1552-4604.1987.tb03041.x
更新日期:1987-05-01 00:00:00
abstract::Semagacestat, a γ-secretase inhibitor, reduces formation of amyloid beta peptide. Two single-dose (140 mg), open-label, randomized, 3-period, crossover studies evaluated the effect of formulation, food, and time of dosing on the pharmacokinetics and pharmacodynamics of semagacestat in healthy participants. The first s...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1177/0091270011407195
更新日期:2012-06-01 00:00:00
abstract::An equation is derived to estimate mean steady state serum concentration (Css) from trough steady state serum concentration (Cmin) which can be used for drugs with either linear or nonlinear pharmacokinetic properties. In 15 subjects receiving phenytoin monotherapy, estimated Css did not differ significantly from meas...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1990.tb03612.x
更新日期:1990-06-01 00:00:00
abstract::Possible effects of multiple-dose administration of atorvastatin on the pharmacokinetics of single-dose antipyrine were evaluated in this drug-drug interaction study. Twelve healthy male volunteers received three 200-mg capsules of antipyrine on days 1 and 22, and two 40-mg atorvastatin tablets in the morning on days ...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1996.tb04212.x
更新日期:1996-04-01 00:00:00
abstract::Calcium channel blocker therapy has proved protective in certain models of ischemic-induced acute renal failure. This effect may be related to the prevention of calcium influx into injured cells or by the vasodilatory effects of verapamil that may result in an improvement in renal blood flow. In the current study, the...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1987.tb03076.x
更新日期:1987-08-01 00:00:00
abstract::The short-term effect of the blockade of the beta-adrenergic receptors on serum lipoproteins and the plasma activities of the enzymes involved in the metabolism of the serum lipoproteins: lipoprotein lipase (LPL), hepatic lipase (HL) and lecithin: cholesterol acyltransferase (LCAT) was evaluated in ten healthy normoli...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1987.tb03052.x
更新日期:1987-07-01 00:00:00
abstract::An open-label, randomized, crossover study was performed in healthy male volunteers to evaluate the potential pharmacokinetic and pharmacodynamic interactions and tolerability of single oral doses of modafinil (200 mg) and dextroamphetamine (10 mg). Blood samples were collected for determination of plasma levels of mo...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1002/j.1552-4604.1998.tb04395.x
更新日期:1998-10-01 00:00:00
abstract::In a double-blind, randomized, crossover study in ten patients with asthma, the effects on specific airway resistance of esmolol, a new ultra-short-acting beta 1-selective adrenoceptor blocker, were compared with those of placebo. Specific airway resistance was measured during increasing doses of esmolol infusion, dur...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1002/j.1552-4604.1986.tb02929.x
更新日期:1986-03-01 00:00:00
abstract::This analysis was conducted to characterize the pharmacokinetics and pharmacodynamics of pegfilgrastim and to develop a pharmacokinetic-pharmacodynamic model to describe the granulopoietic effects of pegfilgrastim and the homeostatic regulation of pegfilgrastim clearance in healthy subjects. Pegfilgrastim serum concen...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1177/0091270006288731
更新日期:2006-07-01 00:00:00
abstract::The electrocardiographic (ECG) effects of rivastigmine treatment were assessed in mild to moderately severe Alzheimer's disease (AD) by analysis of four 26-week, double-blind, multicenter, placebo-controlled, phase III clinical trials. Of an initial 2791 patients, 77% completed treatment. Seventy-one percent required ...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1177/00912700222011490
更新日期:2002-05-01 00:00:00
abstract::The pharmacokinetics, safety, and tolerance of linopiridine ([3,3-bis(4-pyridinylmethyl)-1-phenylindolin-2-one]; DuP 996) a potential therapeutic agent for Alzheimer's disease, were assessed in double-blind, placebo-controlled, randomized studies in which single oral doses were given to 64 healthy young or elderly mal...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1002/j.1552-4604.1995.tb04741.x
更新日期:1995-01-01 00:00:00
abstract::Moricizine, a unique Class I antiarrhythmic agent, was orally administered with and without a meal to 24 healthy male subjects to determine the effect of food on moricizine absorption and bioavailability. Relative to the fasting state, a standardized breakfast delayed the time to peak plasma moricizine concentration (...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1991.tb01912.x
更新日期:1991-09-01 00:00:00
abstract::To evaluate the population pharmacokinetics of valproic acid in children, 97 steady-state serum valproate concentration measurements were gathered during normal, routine, outpatient care of 52 children with epilepsy (1.2-16 years of age). Levels were obtained from patients receiving valproate monotherapy (49%) or valp...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1995.tb04020.x
更新日期:1995-10-01 00:00:00
abstract::Floctafenin (FFn), 2,3-dihydroxypropyl--N--(8--trifluoromethyl--4--quinolyl) anthranilate, a new nonnarcotic analgesic drug, was studied in man, mice, and the isolated perfused rat liver. In all species the drug is rapidly hydrolyzed to floctafenic acid (FFa). In seven volunteer subjects who each received a single ora...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1979.tb01613.x
更新日期:1979-01-01 00:00:00
abstract::The medium-term (16 weeks) effects of the combination of captopril and hydrochlorothiazide (HCTZ) on some metabolic indexes, particularly on plasma lipoproteins, were evaluated in 20 mild to moderate hypertensive outpatients. After a 4-week wash-out period, the subjects were given one tablet of a new commercially avai...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1990.tb03590.x
更新日期:1990-11-01 00:00:00
abstract::This study assessed the efficacy and safety of ketoprofen patch compared with placebo in patients who had rheumatoid arthritis and persistent wrist pain. Patients (N = 676)who had achieved systemic disease control with a disease-modifying antirheumatic drug and/or systemic corticosteroid, but still had persistent wris...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1177/0091270009355813
更新日期:2010-10-01 00:00:00
abstract::The cytomegalovirus (CMV) viral terminase inhibitor letermovir is indicated for prevention of CMV infection in CMV-seropositive allogeneic hematopoietic stem cell transplant recipients. In this analysis, functional variants in solute carrier organic anion transporter family member 1B1 (SLCO1B1), uridine diphosphate-gl...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/jcph.1420
更新日期:2019-09-01 00:00:00
abstract::Cyclosporine (CsA) dosing is based on CsA plasma or blood concentrations measured 12 to 24 hours after drug administration (trough levels). This study evaluated the relationship between the timing of CsA concentrations and subsequent pharmacokinetic parameters to predict an optimal sampling period. Plasma samples were...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1992.tb03798.x
更新日期:1992-11-01 00:00:00
abstract::A general objective of drug-drug interaction (DDI) studies is to determine whether potential interactions of new molecular entities with concomitantly administered other drugs exist and, if DDIs occur, whether dosage adjustments are required. A typical end point for DDI evaluations is the ratio of area under the plasm...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/jcph.1104
更新日期:2018-08-01 00:00:00
abstract::Argatroban, a direct thrombin inhibitor, is metabolized in vitro by CYP3A4/5 and therefore may be susceptible to clinically relevant CYP3A drug interactions. The effect of erythromycin, a potent CYP3A4/5 inhibitor, on the pharmacokinetics and pharmacodynamics of argatroban was evaluated in 14 healthy male volunteers i...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:
更新日期:1999-05-01 00:00:00
abstract::Pharmacological target-mediated drug disposition (TMDD) represents a special source of nonlinear pharmacokinetics, and its occurrence in large-molecule compounds has been well recognized because numerous protein drugs have been reported to have TMDD due to specific binding to their pharmacological targets. Although TM...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/jcph.1763
更新日期:2020-10-19 00:00:00
abstract::Because of the key role blood viscosity plays in the regulation of blood pressure (BP) and the hemorheological effects of pentoxifylline (PTX), this study was conducted to evaluate whether PTX can reduce BP when added to captopril in patients with stage 1 hypertension. In this randomized clinical trial 62 patients wit...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/jcph.1516
更新日期:2020-02-01 00:00:00
abstract::Following oral administration of a single 500-mg dose of cefalexin, serum and urine levels of the antibiotic were determined comparatively in ten normal subjects, ten patients with renal impairment, and ten patients with chronic nephritis on maintenance hemodialysis. In normal subjects, mean serum peak levels (12.0 +/...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1975.tb05918.x
更新日期:1975-10-01 00:00:00
abstract::Recent advances in in vitro metabolism methods have led to an improved ability to predict clinically relevant metabolic drug-drug interactions. To address the relationships of in vitro metabolism data and in vivo metabolism outcomes, the Office of Clinical Pharmacology and Biopharmaceutics in the Center for Drug Evalu...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1177/00912709922008515
更新日期:1999-09-01 00:00:00
abstract::Lormetazepam, an investigational hypnotic, was evaluated for efficacy and withdrawal phenomena in doses of 0.5, 1.0, 1.5, and 2.0 mg in four separate sleep laboratory protocols, each including four placebo baseline nights, seven drug nights, and three placebo withdrawal nights. A moderate degree of efficacy was shown ...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1002/j.1552-4604.1982.tb02645.x
更新日期:1982-11-01 00:00:00
abstract::Lofexidine, an antihypertensive imidazoline derivative, was given to ten hypertensives on both a twice-daily and once-daily regimen, using routine blood pressure measurements and 24-hour Remler recording. Plasma renin activity and catecholamines were measured. After a dose titration with twice-daily doses, the total t...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1981.tb05697.x
更新日期:1981-04-01 00:00:00
abstract::Aprepitant or its prodrug fosaprepitant, in combination with a corticosteroid and a 5-HT(3) receptor antagonist, are used to prevent chemotherapy-induced nausea and vomiting. This study evaluated the effect of fosaprepitant 150 mg on CYP3A4 metabolism. Fosaprepitant 150 mg has been submitted to regulatory agencies for...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1177/0091270010387792
更新日期:2011-12-01 00:00:00