Abstract：
:In this study of the relationship between dose and plasma concentration of verapamil, controlled-release verapamil in doses of 120 mg, 180 mg, 360 mg, and 540 mg were examined. The 48 study subjects received verapamil daily during each of the 4 sequential 5-day dosing segments. Blood samples were collected frequently to obtain first-dose and steady-state (fifth dose) concentration profiles of verapamil. Plasma concentrations of R- and S-verapamil and R- and S-norverapamil were measured by stereospecific assay. Statistical comparisons of pharmacokinetic parameters and mean differences between doses were performed with analysis of variance models. At steady state, area under the concentration-time curve (AUC) values for R- and S-verapamil at both the 120-mg and 180-mg doses were about 1.5 times higher than the corresponding first-dose values. After both first and fifth doses, pharmacokinetic parameters for all four analytes were dose proportional between the 120-mg and 180-mg doses. A dose-proportional relationship also was found between the 360-mg and 540-mg dose levels. However, nonlinearity was found between the 180-mg dose and higher doses, suggesting saturable metabolic pathways. The dose-proportional relationship between the 360-mg and 540-mg doses suggests that other first-order metabolic pathways become dominant. Although results from this study are partially consistent with previously reported nonlinear verapamil kinetics, this is the first clinical study to demonstrate a dose-proportional relationship for verapamil at both low and high input rates (mg/hr). In addition, first-order disposition pathways of verapamil are probably nonexistent at medium input rates and become dominant at higher input rates.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Gupta SK,Hwang S,Atkinson L,Longstreth Jdoi
10.1002/j.1552-4604.1996.tb04148.xsubject
Has Abstractpub_date
1996-01-01 00:00:00pages
25-34issue
1eissn
0091-2700issn
1552-4604journal_volume
36pub_type
杂志文章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：:The influence of the method of cimetidine administration on theophylline disposition was studied in nine healthy, cigarette smoking male volunteers. The treatment phases consisted of: A) theophylline alone, B) theophylline plus intermittent cimetidine therapy (300 mg IV every 6 hr), and C) theophylline in combination ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1989.tb03398.x
更新日期：1989-07-01 00:00:00
abstract：:This study aimed to evaluate the safety and tolerability of intravenous (IV) levetiracetam (LEV) as a monotherapy in children aged 1 month-16 years and to explore the pharmacokinetics (PK) of IV LEV and the time to seizure after IV then oral administration of LEV in pediatric children with epilepsy. Children diagnosed...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/jcph.1282
更新日期：2018-12-01 00:00:00
abstract：:Heparin-induced thrombocytopenia (HIT) is a high-risk adverse drug reaction because of its associated risk of life- and limb-threatening thrombosis. Rivaroxaban may be considered as an ideal nonheparin anticoagulant alternative for the management of HIT. In this preliminary retrospective study, the efficacy and safety...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.1635
更新日期：2020-10-01 00:00:00
abstract：:The antihypertensive effect of a new beta-adrenergic receptor blocker, l-bunolol, was evaluated in 11 hospitalized hypertensive patients of whom four belonged to the high-renin, five to the normal-renin, and two to the low-renin subgroup. There was a significant decrease in blood pressure in most patients, often to no...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1977.tb04615.x
更新日期：1977-05-01 00:00:00
abstract：:For more than a decade, first responders and the general public have been able to treat suspected opioid overdoses using an improvised nasal naloxone device (INND) constructed from a prefilled syringe containing 2 mg of naloxone (1 mg/mL) attached to a mucosal atomization device. In recent years, the U.S. Food and Dru...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1002/jcph.1401
更新日期：2019-08-01 00:00:00
abstract：:Rapidly inflating health care costs limit patient care, and prescription drug costs constitute a major component of this expenditure. This study examines attitudes toward and knowledge of prescription drug costs of primary care physicians. Access to information about drug costs and implications for medical education a...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1994.tb04726.x
更新日期：1994-12-01 00:00:00
abstract：:The bioavailability and pharmacokinetics of dilevalol following oral and intravenous administration were investigated in 12 healthy male volunteers. Dilevalol HCl was administered as a 200-mg oral tablet and a 50-mg intravenous infusion using a randomized cross-over design. Blood and urine samples were collected over ...
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.1552-4604.1988.tb03189.x
更新日期：1988-07-01 00:00:00
abstract：:The cancer stem cell paradigm, the epithelial-to-mesenchymal transition and its converse, the mesenchymal-to-epithelial transition, have reached convergence. Implicit in this understanding is the notion that cancer cells can change state, and with such change come bidirectional alterations in motility, proliferative a...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1002/jcph.486
更新日期：2015-06-01 00:00:00
abstract：:Taranabant is a cannabinoid-1 receptor inverse agonist for the treatment of obesity. This study evaluated the safety, pharmacokinetics, and pharmacodynamics of taranabant (5, 7.5, 10, or 25 mg once daily for 14 days) in 60 healthy male subjects. Taranabant was rapidly absorbed, with a median t(max) of 1.0 to 2.0 hours...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1177/0091270008317591
更新日期：2008-06-01 00:00:00
abstract：:Twenty-three normal volunteers who received morphine sulphate (MS Contin) with naltrexone completed this randomized, analytically blinded, two-way crossover comparison of the bioavailability of one 200-mg oral controlled-release morphine sulfate tablet with two 100-mg MSC tablets. Morphine effects were blocked by thre...
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.tb04094.x
更新日期：1995-05-01 00:00:00
abstract：:A randomized, single-blind, placebo-controlled, parallel-group study was conducted to assess the effect of age and gender on the pharmacokinetics and pharmacodynamics of rivaroxaban - an oral, direct Factor Xa inhibitor. Subjects (n = 34) were enrolled into four groups: young males or females (aged 18-45 years) and el...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1002/jcph.5
更新日期：2013-03-01 00:00:00
abstract：:CPX-351, a dual-drug liposomal encapsulation of cytarabine and daunorubicin at a synergistic ratio, is approved in the United States for adults with newly diagnosed therapy-related acute myeloid leukemia or acute myeloid leukemia with myelodysplasia-related changes. Population pharmacokinetics analyses were performed ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.1366
更新日期：2019-05-01 00:00:00
abstract：:The 30-minute ratio of 1'-hydroxymidazolam:midazolam plasma concentrations has been used as a measure of midazolam clearance in liver transplant patients. This study determined if a single concentration of 1'-hydroxymidazolam or the ratio of 1'-hydroxymidazolam:midazolam could be used to predict midazolam clearance in...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1177/009127002401382614
更新日期：2002-10-01 00:00:00
abstract：:Antinociception by nonsteroidal antiinflammatory drugs, notably diclofenac and S(+)-ibuprofen, has traditionally been attributed to peripheral tissue cyclooxygenase inhibition. This study investigates the potential role of the nitric oxide system for the central antinociceptive effects of diclofenac, S(+)-, and R(-)-i...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：
更新日期：1996-12-01 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：:This study evaluated the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of a novel depot formulation of abarelix, a new gonadotropin-releasing hormone (GnRH) antagonist. This was an open-label, sequential two-phase study in healthy male subjects ages 50 to 75. Subjects received a single intramuscular (IM) do...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1177/0091270004264920
更新日期：2004-05-01 00:00:00
abstract：:Rasagiline is an irreversible monoamine oxidase type B (MAO-B) inhibitor indicated for the treatment of the signs and symptoms of idiopathic Parkinson disease as initial monotherapy and as adjunct therapy to levodopa. Pharmacologic inhibition of monoamine oxidase type A (MAO-A), but not MAO-B, poses a risk of the "che...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1177/0091270011406279
更新日期：2012-05-01 00:00:00
abstract：:The efficacy of intravenously administered metoprolol, a cardioselective beta-adrenergic blocking agent, was evaluated in the treatment of supraventricular tachyarrhythmias in 16 patients. The arrhythmias that were treated were atrial fibrillation (11 patients), atrial flutter (2 patients), supraventricular tachycardi...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1991.tb03765.x
更新日期：1991-08-01 00:00:00
abstract：:The rate of change of plasma procainamide concentration during 36 hours of constant-rate intravenous infusion was examined in five acute myocardial infarction patients. It was observed that a steady-state plasma concentration was established in about 16 hours, which is consistent with simulations of plasma concentrati...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1978.tb02455.x
更新日期：1978-08-01 00:00:00
abstract：:The objective of this study was to characterize the population pharmacokinetics of enfuvirtide in HIV-1-infected children and adolescents. HIV-infected patients received combination antiretroviral therapy, including enfuvirtide 2.0 mg/kg subcutaneously, twice daily. Serial and trough blood samples were collected up to...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,多中心研究
doi：10.1177/0091270006299089
更新日期：2007-04-01 00:00:00
abstract：:Two populations of critical care patients were studied using indices of renal tubular damage (beta 2-microglobulin, enzymes, casts) and indices of glomerular filtration (creatinine, creatinine clearance). The purpose of these studies had been initially to elucidate the type of renal failure typical of the critically i...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1983.tb01793.x
更新日期：1983-10-01 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：:Response to statin therapy is often unpredictable because of variability in metabolism and transport. In the recently created organic anion transporting-polypeptide 1b2 (Oatp1b2/Slco1b2)-null mice, the investigators found significantly lower liver-to-plasma ratios compared with controls for atorvastatin (16.0 ± 5.1 vs...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1177/0091270011422815
更新日期：2012-11-01 00:00:00
abstract：:Anemia is a well-known RBV-related event in HCV therapy which is exacerbated by the addition of telaprevir and boceprevir. This retrospective study evaluated and compared ribavirin exposure and parameters able to influence hemoglobin decrease in a large population of patients treated with dual or triple therapy. Patie...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.454
更新日期：2015-05-01 00:00:00
abstract：:Renal electrolyte excretion patterns were determined in nonedematous healthy volunteers following bumetanide and furosemide in two separate clinical studies. In study 1, intravenous bumetanide was administered to 24 subjects at four dose levels. In study 2, bumetanide (1 or 2 mg) or furosemide (40 or 80 mg) was admini...
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.1552-4604.1981.tb05671.x
更新日期：1981-11-01 00:00:00
abstract：:Isosorbide dinitrate is one of the most commonly prescribed medications for the treatment of ischemic heart disease. It has been demonstrated to be ineffective relative to placebo when taken inappropriately. This study objectively documents the magnitude and nature of compliance in 68 ambulatory patients who were pres...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1996.tb04222.x
更新日期：1996-07-01 00:00:00
abstract：:The bioavailability and pharmacologic activity of tablets containing micronized spironolactone chemical (median particle size 2.21 micrometers) were compared to those of tablets made from standard spironolactone chemical (median particle size 78.8 micrometers) in healthy men. Apart from particle size, all features of ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1982.tb02694.x
更新日期：1982-08-01 00:00:00
abstract：:The safety and efficacy of step-one therapy with enalapril, a new angiotensin-converting enzyme inhibitor, and metoprolol were compared in a double-blind, multicenter study involving 150 patients who had mild to moderate essential hypertension. After a four-week period of placebo run-in, therapy was initiated with twi...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1987.tb03050.x
更新日期：1987-07-01 00:00:00
abstract：:Tinidazole is a potent nitroimidazole compound active against, and used to treat, Trichomonas vaginalis infections in males and females. Speculation exists in the literature that observed differences in tinidazole plasma concentrations between males and females may be due to sex-mediated pharmacokinetic differences. T...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1982.tb02650.x
更新日期：1982-11-01 00:00:00
