Abstract:
:HMR1031 is a potent and specific antagonist of the integrin VLA-4 (alpha4beta1) binding to vascular cell adhesion molecule-1 (VCAM-1) and fibronectin. HMR1031 is an inhaled drug being developed for the treatment of asthma using an Ultrahaler dry-powder inhalation device. A pharmacoscintigraphic study of HMR1031 suggests a lung deposition of approximately 25% and gastrointestinal tract deposition of approximately 75%. Since oral absorption may be contributing to systemic plasma concentrations, the effect of food on HMR1031 was assessed. This was a single-dose (3 mg), open-label, randomized, two-way crossover (fasted vs. fed) study in 8 healthy male subjects. Blood samples were collected at predose and up to 24 hours postdose. Plasma concentrations were determined by the LC/MS/MS method. HMR1031 was rapidly absorbed, with median tmax values of 1.0 and 0.75 hours under fasted and fed conditions, respectively. Under fasted conditions, mean AUCinfinity and Cmax values were 16.4 ng x h/mL and 4.56 ng/mL, respectively. Under fed conditions, mean AUCinfinity and Cmax values decreased to 11.7 ng x h/mL and 2.81 ng/mL, respectively. The mean terminal elimination half-life (t1/2) for both treatment groups was similar (2.7 h). HMR1031 population estimates of the apparent clearance, apparent volume of distribution, and absorption rate were 225 L/h (4.1% coefficient of variation [CV]), 44.5 L (26% CV), and 0.340 h-1 (7.0% CV), respectively. Food is a significant covariate on clearance. These data suggest that food unexpectedly decreases the systemic exposure of inhaled HMR1031 by approximately 30%, probably due to increased liver blood flow and increased biliary excretion. This decrease in systemic exposure is unlikely to affect the topical effect of the drug but may result in increased variability in plasma pharmacokinetics. The disposition and food effect of HMR1031 can be described using mixed-effect modeling.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Shah B,Jensen BK,Zhang J,Hunt T,Rohatagi Sdoi
10.1177/0091270003258172subject
Has Abstractpub_date
2003-12-01 00:00:00pages
1341-9issue
12eissn
0091-2700issn
1552-4604pii
43/12/1341journal_volume
43pub_type
临床试验,杂志文章,随机对照试验abstract::This study assesses the magnitude and duration of action of three different oral doses of the new orally active angiotensin-converting enzyme (ACE) inhibitor RO 312848 (cilazapril, Hoffman-LaRoche, Nutley, NJ) on blood pressure and plasma ACE levels. Twelve hypertensive patients were separated into two groups: Group A...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1002/j.1552-4604.1988.tb03194.x
更新日期:1988-07-01 00:00:00
abstract::A total of 125 outpatients with moderate to severe pain after surgical removal of one impacted third molar were randomly assigned to receive dexketoprofen trometamol 12.5 or 25 mg or dipyrone 575 mg. For first-dose assessments, patients rated their pain intensity and its relief at regular intervals. From 60 min post d...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/jcph.1998.38.s1.55
更新日期:1998-12-01 00:00:00
abstract::Of 17,068 hospitalized medical patients monitored in a drug surveillance program, 616 (3.6 per cent) received pentazocine hydrochloride orally and 816 (4.8 per cent) received pentazocine lactate parenterally during one or more admissions. Unsatisfactory analgesic efficacy as judged by each patient's physician was near...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1975.tb02357.x
更新日期:1975-02-01 00:00:00
abstract::Adherence to microbicide gel use is critical to optimizing effectiveness in preventing human immunodeficiency virus transmission. The authors hypothesized that ester taggants added to vaginal gels would generate exhaled alcohol and ketone metabolites and provide a "breath test" for vaginal gel use. This 2-arm (vaginal...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1177/0091270011434157
更新日期:2013-01-01 00:00:00
abstract::Concentrations in breast milk of medications used during general anesthesia were measured to determine whether interruption of breast-feeding was indicated. Breast milk and maternal blood samples were obtained from nine women undergoing tubal sterilization under general anesthesia. Concentrations of methohexital, mepe...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1997.tb04780.x
更新日期:1997-03-01 00:00:00
abstract::Inhaled glucocorticoids induce therapeutic and adverse systemic effects via the same types of receptors. Analysis of the pharmacokinetic/pharmacodynamic parameters of inhaled glucocorticoids generates a risk-benefit value (RBV). Targeted efficacy with minimal adverse effects helps to quantify an appropriate RBV. High ...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1177/0091270003260334
更新日期:2004-01-01 00:00:00
abstract::The renin-angiotensin system (RAS) functions as a primary regulator in the short-term and long-term control of blood pressure. Pharmacologic inhibition of the RAS with angiotensin-converting enzyme (ACE) inhibition is effective for treating systemic hypertension and congestive heart failure. As a more specific therapy...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1002/j.1552-4604.1994.tb04000.x
更新日期:1994-09-01 00:00:00
abstract::UCN-01 is a protein kinase inhibitor under development as a novel anticancer drug. The initial pharmacologic features in patients were not predicted from preclinical experiments. The distribution volume and the systemic clearance were much lower than those in experimental animals (mice, rats, and dogs), and the elimin...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1177/0091270005274549
更新日期:2005-04-01 00:00:00
abstract::Alkamides are suspected to contribute to the activity of Echinacea preparations. They are mainly derived from undeca- and dodecanoic acid and differ in the degree of unsaturation and the configuration of the double bonds. In total, 6 alkamides have been isolated from the roots of Echinacea angustifolia as major lipoph...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1177/0091270004273493
更新日期:2005-06-01 00:00:00
abstract::Precision medicine in oncology is the result of an increasing awareness of patient-specific clinical features coupled with the development of genomic-based diagnostics and targeted therapeutics. Companion diagnostics designed for specific drug-target pairs were the first to widely utilize clinically applicable tumor b...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1002/jcph.765
更新日期:2016-12-01 00:00:00
abstract::The objective of this randomized clinical trial was to compare steady-state gestational RBC and plasma folate concentrations in pregnant women supplementing daily with 1.1 mg (regular dose) vs. 5 mg (high dose) folic acid. Thirty-seven pregnant women, who were not previously taking folic acid, were enrolled in this op...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1002/jcph.387
更新日期:2015-02-01 00:00:00
abstract::Etoricoxib is a potent selective COX-2 inhibitor in man. Ex vivo whole-blood assays assessed COX-2 inhibition after oral administration of etoricoxib in single (5-500 mg) and multiple (25-150 mg) once-daily doses to healthy human subjects. A separate study examined ex vivo gastric mucosal PGE2 synthesis after etoricox...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:2003-06-01 00:00:00
abstract::Despite a paucity of data, the role of intravenous lidocaine (IVLI) as adjunctive analgesia in the intensive care unit (ICU) seems promising due to a low potential to contribute to respiratory depression. A retrospective chart review was conducted to evaluate the safety and effectiveness of IVLI for the treatment of p...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1002/jcph.874
更新日期:2017-07-01 00:00:00
abstract::Oral administration of docetaxel is an attractive alternative for conventional intravenous (IV) administration. The low bioavailability of docetaxel, however, hinders the application of oral docetaxel in the clinic. The aim of the current study was to develop a population pharmacokinetic (PK) model for docetaxel and r...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/jcph.1532
更新日期:2020-03-01 00:00:00
abstract::ABT-761 is a second-generation 5-lipoxygenase inhibitor in clinical development for the treatment of asthma. The effects of ABT-761 on the pharmacokinetics of an oral contraceptive were assessed in 21 female adult volunteers in a phase I, multiple-dose, open-label study. Subjects received a single dose of oral contrac...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1002/j.1552-4604.1998.tb04472.x
更新日期:1998-07-01 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::Mavrilimumab is a fully human monoclonal antibody that binds to granulocyte-macrophage colony stimulating factor receptor α (GM-CSFRα) with high affinity and specificity and has potential application in various inflammatory diseases. The objective of this investigation was to develop a mechanistic population model to ...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1177/0091270011412964
更新日期:2012-08-01 00:00:00
abstract::The therapeutic and biochemical effects of two commonly employed diuretic preparations were compared in a double-blind fashion in 32 patients with congestive heart failure. At the doses employed, furosemide and a fixed combination of spironolactone and hydrochlothiazide maintained control of the clinical manifestation...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1002/j.1552-4604.1977.tb04625.x
更新日期:1977-07-01 00:00:00
abstract::Aprepitant, a neurokinin antagonist, is an effective antiemetic agent in chemotherapy for delayed nausea and vomiting. The study objective was to evaluate the pharmacokinetics of aprepitant and concurrent cyclophosphamide (CY), often a component of hematopoietic stem cell transplant (HSCT) conditioning regimen, in can...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1177/0091270011398243
更新日期:2012-04-01 00:00:00
abstract::Faldaprevir is a potent hepatitis C virus (HCV) NS3/4A protease inhibitor and an inhibitor of UDP-glucuronosyltransferase-1A1 (UGT1A1), which is involved in raltegravir clearance. Raltegravir, an HIV integrase inhibitor, may be used in combination with HCV treatment in HCV/HIV co-infected patients. In this open-label,...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/jcph.418
更新日期:2015-04-01 00:00:00
abstract::Recently, a new latanoprost ophthalmic solution containing cyclodextrins was developed. The purpose of the present work was to compare the stability, clinical efficacy, and adverse effect profile of this formulation with the innovator product. The innovator formulation was stable at 4 degrees C but exhibited degradati...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1177/0091270006292626
更新日期:2007-01-01 00:00:00
abstract::Ixekizumab (LY2439821), a humanized immunoglobulin G subclass 4 (IgG4) monoclonal antibody that selectively binds and neutralizes interleukin (IL) 17A has demonstrated efficacy in the treatment of psoriasis. A population pharmacokinetics-pharmacodynamics model was developed using NONMEM 7.2 to describe the temporal re...
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.312
更新日期:2014-10-01 00:00:00
abstract::The selective T-cell costimulation modulator abatacept is approved for treatment of adult rheumatoid arthritis (RA) and polyarticular juvenile idiopathic arthritis (pJIA; 6-17 years [intravenous] and 2-17 years [subcutaneous]). An extrapolation approach was taken to determine subcutaneous weight-tiered doses of abatac...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/jcph.1797
更新日期:2020-12-07 00:00:00
abstract::A clinical study of bumetanide, a new diuretic, was conducted in outpatients of a cardiology clinic to determine its long-term effectiveness and safety in the treatment of peripheral edema due to congestive heart failure. The drug was administered for at least 24 weeks on a selected group of 34 patients. The patients ...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1981.tb05685.x
更新日期:1981-11-01 00:00:00
abstract::Atorvastatin is a common option among the HMG-CoA reductase inhibitors for the treatment of lipid disorders because of its excellent lipid-lowering efficacy and overall safety profile. Although these agents can rarely cause rhabdomyolysis by themselves, macrolides, among other agents, have been demonstrated to increas...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:2002-04-01 00:00:00
abstract::The in vitro plasma protein binding of warfarin was evaluated by ultrafiltration in plasma from seven normal subjects and seven patients with varying degrees of renal dysfunction. The unbound, or free, warfarin fraction was twice as high in the plasma samples withdrawn from patients with renal impairment than in the s...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:
更新日期:1976-10-01 00:00:00
abstract::A selective thromboxane A2 (TXA2) receptor blocking agent, vapiprost, was orally administered to healthy male Japanese volunteers to investigate the pharmacokinetic and pharmacodynamic properties. The time-profile of vapiprost concentration in plasma was determined and the effects of the drug on platelet aggregation i...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1991.tb01917.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::The aim of these two studies was to evaluate the safety and pharmacokinetics of oral nalmefene, a new orally effective opioid antagonist. In the first study, single ascending doses of 50, 100, 200, and 300 mg of nalmefene HCl were administered in double-blind fashion to four groups of healthy men. There were six subje...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1002/j.1552-4604.1987.tb02191.x
更新日期:1987-03-01 00:00:00
abstract::The population pharmacokinetic (PK) profile of oral clonidine was characterized in newborns with neonatal abstinence syndrome, and significant covariates affecting its PK parameters were identified. Plasma clonidine concentration data were obtained from a clinical trial in which 36 newborns, aged 1 to 25 days (postnat...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1177/0091270010370587
更新日期:2011-04-01 00:00:00