Abstract:
:Triamcinolone acetonide (TCA) is a corticosteroid that is frequently used in the treatment of asthma. After inhalation, TCA can become systemically available when the inhaled formulation is swallowed, causing undesirable systemic effects. A clinical study was conducted to determine the systemic side effects of TCA after intravenous (2 mg as phosphate ester), oral (5 mg), and inhaled (2 mg) administration. Blood samples were collected at appropriate times over 24 hours, and TCA concentrations in plasma were measured by high-performance liquid chromatography and radioimmunoassay. Free drug concentrations were determined by ultrafiltration for correlating pharmacokinetics and pharmacodynamics. The free fraction of TCA (+/- standard deviation) was 29.0 +/- 1.3% and was independent of the investigated concentration range up to 1,000 ng/mL. Pharmacodynamic parameters were determined by monitoring lymphocytes, granulocytes, and cortisol. Pharmacokinetic/pharmacodynamic modeling was performed using a modified Emax model for lymphocytes and granulocytes. A novel linear release rate model was used to characterize the cortisol data. The E50 values determined from all three pharmacodynamic endpoints were not significantly different for the three treatments, indicating that these effects can be explained based on systemic steroid concentrations.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Rohatagi S,Hochhaus G,Mollmann H,Barth J,Galia E,Erdmann M,Sourgens H,Derendorf Hdoi
10.1002/j.1552-4604.1995.tb04045.xsubject
Has Abstractpub_date
1995-12-01 00:00:00pages
1187-93issue
12eissn
0091-2700issn
1552-4604journal_volume
35pub_type
临床试验,杂志文章,随机对照试验abstract::Psychoactive drugs are often widely used before tolerance and dependence is fully appreciated. Tolerance to cannabis-induced cardiovascular and autonomic changes, decreased intraocular pressure, sleep and sleep EEG, mood and behavioral changes is acquired and, to a great degree, lost rapidly with optimal conditions. M...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1981.tb02589.x
更新日期:1981-08-01 00:00:00
abstract::A vast and continuously growing amount of material on drugs exists in the literature to read and evaluate. Frequently, the papers and their recommendations are conflicting and contradictory. Readers are faced with the dilemma of deciding what to believe. The need for evidence-based medicine as a foundation for optimal...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:2002-09-01 00:00:00
abstract::Inflammatory conditions, such as rheumatoid arthritis, reduce response to calcium channel and beta-adrenergic antagonists but not the angiotensin II type 1 receptor (AT(1)R) antagonist valsartan. Inflammation also reduces clearance of some drugs or active metabolite, thereby reducing response. Active (n = 14) and cont...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1177/0091270006292163
更新日期:2006-11-01 00:00:00
abstract::Esmolol hydrochloride was administered by constant-rate continuous infusion to 10 patients undergoing hypothermic cardiopulmonary bypass for coronary artery revascularization surgery. After a suitable loading dose, the esmolol infusion was started approximately 30 minutes before bypass and was stopped 10 minutes after...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1993.tb04670.x
更新日期:1993-04-01 00:00:00
abstract::Lomitapide is a microsomal triglyceride transfer protein inhibitor approved as an adjunctive treatment for adult patients with homozygous familial hypercholesterolemia. Lomitapide is extensively metabolized via cytochrome P450 3A (CYP3A) and is a weak CYP3A inhibitor. Two phase 1 open-label, randomized (1:1), 2-arm dr...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1002/jcph.581
更新日期:2016-01-01 00:00:00
abstract::Universally present but overlooked cavities or pockets in long-lived biopharmaceuticals, such as monoclonal antibodies (mAbs), are capable of binding small drugs. Such direct interactions can alter the pharmacokinetics of drugs and potentially affect clinical outcome. The extreme differences in the pharmacokinetic pro...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1177/0091270008323259
更新日期:2008-10-01 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::This study was designed to determine the pharmacokinetics and dose proportionality of clentiazem (CLZ) after single doses (SD) of 20, 40, and 80 mg and multiple dose administration (SS) of 40, 80, and 160 mg/day for 5 days. The study was an open-label, randomized four-period complete crossover design. Twenty-four heal...
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.1552-4604.1993.tb04684.x
更新日期:1993-05-01 00:00:00
abstract::The approved antiretroviral drugs, emtricitabine and tenofovir disoproxil fumarate, were considered good candidates for a fixed-dose combination product that could be administered as a single pill once daily (qd), thereby simplifying existing treatment regimens and promoting patient adherence. As both drugs are extens...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1177/0091270007300951
更新日期:2007-06-01 00:00:00
abstract::An open-label study evaluated the effect of steady-state venlafaxine on the single-dose pharmacokinetic profile of risperidone, a CYP2D6 substrate; its active metabolite, 9-hydroxyrisperidone; and the total active moiety (risperidone plus 9-hydroxyrisperidone). Thirty healthy subjects received a 1 mg oral dose of risp...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:
更新日期:1999-03-01 00:00:00
abstract::Nineteenth century ophthalmology, characterized by significant gains in diagnostic techniques, provided the basis for great advancements in treatment during the 20th century. Drug therapy at the turn of the century was empiric, palliative, and often toxic. The development of ocular pharmacology during the 20th century...
journal_title:Journal of clinical pharmacology
pub_type: 历史文章,杂志文章
doi:10.1177/00912700022009710
更新日期:2000-09-01 00:00:00
abstract::Understanding how inhibition of cytochrome P4503A (CYP3A) affects the metabolism of a new drug is critical in determining if a clinically relevant drug interaction will occur. Diltiazem interaction studies assess a given compound's sensitivity to moderate CYP3A inhibition. The present study compared the effect differe...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1177/0091270010387141
更新日期:2011-11-01 00:00:00
abstract::We administered 0.5-and 1.0-mg doses of bumetanide intravenously to eight normal subjects with and without pretreatment with probenecid. Probenecid did not effect either the cumulative response or the time course of response of bumetanide. These results are in contrast to results reported in dogs but consistent with s...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1981.tb01772.x
更新日期:1981-07-01 00:00:00
abstract::Clinical pharmacologists, neurologists, internists, and all health care givers must consider the efficacy, safety, and side effect profile of a given antiepileptic drug (AED) when determining which drug is best for a given patient. The first purpose of this paper is to address whether the "new" AEDs have advantages ov...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:
更新日期:2003-05-01 00:00:00
abstract::To assess the effect of orlistat on the pharmacokinetics and pharmacodynamics of warfarin, a third-party blind, placebo-controlled, randomized, two-way crossover study was performed in 12 healthy volunteers. Each participant received single 30-mg oral doses of racemic warfarin sodium (Coumadin; DuPont Pharma, Wilmingt...
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.1552-4604.1996.tb04232.x
更新日期:1996-07-01 00:00:00
abstract::In a double-blind, placebo-controlled study, an attempt was made to evaluate butaclamol in chronic schizophrenic patients using chlorpromazine (CPZ) as the standard comparative drug. With doses up to 50 mg/day, butaclamol was shown to have significant antipsychotic activity comparable to CPZ but with a much higher inc...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1002/j.1552-4604.1977.tb05646.x
更新日期:1977-08-01 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::Glucagon is a counter-regulatory hormone that is classically used to treat hypoglycemia. However, it can elicit the generation of cAMP within the myocardium to cause positive inotropic and chronotropic effects without the need for beta-1 adrenoceptor stimulation. Glucagon has been used extensively to treat beta-blocke...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1999-05-01 00:00:00
abstract::BIA 10-2474 (a fatty acid amide hydrolase inhibitor) was evaluated in a first-in-human phase 1 study in normal volunteers to assess safety/tolerability, pharmacokinetics, pharmacodynamics, and food effect. The dose-escalation process consisted of a single-ascending-dose phase (SAD) and multiple-ascending-dose phase (M...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1002/jcph.889
更新日期:2017-06-01 00:00:00
abstract::A method of estimating the elimination half-life of a drug at any selected serum concentration when the Km and Vmax of that drug are known is described. The method was validated in six patients by determining their Km and Vmax values for phenytoin, using data obtained at two serum concentrations and then using the Km ...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1987.tb03022.x
更新日期:1987-04-01 00:00:00
abstract::Safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of ATR-107, a fully human monoclonal anti-IL-21 receptor (IL-21R) antibody, administered as ascending single doses, subcutaneously or intravenously, was evaluated in a placebo-controlled, double-blind trial in healthy subjects. The dose levels were...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1002/jcph.158
更新日期:2014-01-01 00:00:00
abstract::Ofatumumab is a human monoclonal antibody that binds to a unique CD20 epitope on the surface of B lymphocytes, resulting in efficient lysis of CD20-expressing cells via complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity. The potential effect of ofatumumab on cardiac repolarization and ...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1002/jcph.376
更新日期:2015-01-01 00:00:00
abstract::Lemborexant is a novel orexin receptor antagonist approved in the United States and Japan for the treatment of insomnia. This article describes the population pharmacokinetics (PK) of lemborexant and the relationship of its daily steady-state exposure (Cav,ss ) to the probability of most frequent treatment-emergent ad...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/jcph.1683
更新日期:2020-12-01 00:00:00
abstract::Numerous physiologic variations, including urinary protein excretion, low serum albumin concentrations, and reductions in kidney function (clearance), exist in patients with glomerulonephritis. These factors could alter the disposition of numerous drugs. The purpose of the current article was to review the influence o...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1177/0091270011413895
更新日期:2012-01-01 00:00:00
abstract::In many industrialized nations, the elderly comprise the fastest growing subpopulation and constitute an increasing proportion of the total population compared to other age groups. The elderly use a disproportionately larger amount of health care resources since they experience a higher incidence of disease-related mo...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1999-11-01 00:00:00
abstract::These studies were conducted to evaluate the pharmacokinetics of several retinoids after meal consumption or vitamin A supplementation to establish a reference for future assessment of teratogenic risks of retinoid therapeutic agents. In the first study, 36 healthy young female volunteers consumed single meals contain...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1996.tb04253.x
更新日期:1996-09-01 00:00:00
abstract::The absolute bioavailability of oral melatonin tablets was studied in 12 normal healthy volunteers. Subjects were administered, in a randomized crossover fashion, melatonin 2 mg intravenously and 2 and 4 mg orally. Blood was sampled over approximately eight (estimated) half-lives. Both the 2 and the 4 mg oral dosages ...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1177/00912700022009422
更新日期:2000-07-01 00:00:00
abstract::The effect of rosuvastatin on the pharmacokinetics of digoxin was assessed in 18 healthy male volunteers in this double-blind, randomized, two-way crossover trial. Volunteers were dosed with rosuvastatin (40 mg once daily) or placebo to steady state before being given a single dose of digoxin 0.5 mg. Blood and urine s...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1177/0091270002042012008
更新日期:2002-12-01 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
abstract::Thrombomodulin alfa is the recombinant extracellular domain of human thrombomodulin, which shows anticoagulation activity. To elucidate the pharmacokinetics of thrombomodulin alfa in patients with disseminated intravascular coagulation (DIC), population pharmacokinetic (PPK) analysis was performed using plasma concent...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1177/0091270010381900
更新日期:2011-09-01 00:00:00