Abstract：
:Axitinib is a potent and selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, approved for second-line therapy for advanced renal cell carcinoma (RCC). Axitinib population pharmacokinetic and pharmacokinetic/pharmacodynamic relationships were evaluated. Using nonlinear mixed effects modeling with pooled data from 383 healthy volunteers, 181 patients with metastatic RCC, and 26 patients with other solid tumors in 17 trials, the disposition of axitinib was best described by a 2-compartment model with first-order absorption and a lag time, with estimated mean systemic clearance (CL) of 14.6 L/h and central volume of distribution (V(c)) of 47.3 L. Of 12 covariates tested, age over 60 years and Japanese ethnicity were associated with decreased CL, whereas V(c) increased with body weight. However, the magnitude of predicted changes in exposure based on these covariates does not warrant dose adjustments. Multivariate Cox proportional hazard regression and logistic regression analyses showed that higher exposure and diastolic blood pressure were independently associated with longer progression-free and overall survivals and higher probability of partial response in metastatic RCC patients. These findings support axitinib dose titration to increase plasma exposure in patients who tolerate axitinib, and also demonstrate diastolic blood pressure as a potential marker of efficacy.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Rini BI,Garrett M,Poland B,Dutcher JP,Rixe O,Wilding G,Stadler WM,Pithavala YK,Kim S,Tarazi J,Motzer RJdoi
10.1002/jcph.73subject
Has Abstractpub_date
2013-05-01 00:00:00pages
491-504issue
5eissn
0091-2700issn
1552-4604journal_volume
53pub_type
杂志文章abstract：:The objective of this study was to investigate the gene expression signature of monocyte/macrophages and the pleiotropic effects of atorvastatin on monocytes in atherosclerotic patients. Forty patients with coronary heart diseases were randomly assigned to double-blind therapy with either 20 or 80 mg per day of atorva...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1177/0091270009340889
更新日期：2010-03-01 00:00:00
abstract：:Olanzapine is an atypical antipsychotic medication indicated for the treatment of schizophrenia and other manifestations of psychotic illness. Common side effects include somnolence, constipation, weight gain, and postural hypotension. The authors report a case of hypotension accompanied by bradycardia in a normal, he...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1177/0091270002042001013
更新日期：2002-01-01 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：: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：:Sixteen essential hypertensive patients were entered into a protocol assessing the effect of Spirapril, an angiotensin-converting enzyme (ACE) inhibitor, on blood pressure, the renin-aldosterone system, and renal function. Specifically monitored before, during 6 weeks, and 6 months of Spirapril therapy were plasma ren...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1993.tb04668.x
更新日期：1993-04-01 00:00:00
abstract：:The pharmacokinetics and pharmacodynamics of intravenous famotidine were evaluated in 10 infants ranging from 5 to 19 days of age who had a therapeutic indication for the prophylactic treatment of stress ulceration. After a 0.5-mg/kg infusion of famotidine, timed serum (n = 6), urine (24-hour collection), and repeated...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：
更新日期：1998-12-01 00:00:00
abstract：:Vitamin B6 has been known to possess antiemetic effects since 1942. This water soluble compound has several forms in the circulation including pyridoxine, pyridoxal, and pyridoxal phosphate. The active antiemetic form of vitamin B6 is unknown. This was a pre-specified substudy of a randomized, placebo-controlled trial...
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.369
更新日期：2014-12-01 00:00:00
abstract：:This trial was conducted to evaluate the pharmacokinetics and safety of a sodium oxybate (gamma-hydroxybutyrate [GHB]) oral solution in narcoleptic patients after acute and chronic treatment. An open-label, two-period, two-treatment study design was used. Trial subjects included 13 patients with polysomnographically c...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1177/0091270003262795
更新日期：2004-03-01 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 study outlines the attempts of four states (Louisiana, Kansas, Wisconsin, and Michigan) to restrict anorectic prescriptions. The actions in these four states exemplify the various mechanisms used in regulating anorectics, ranging from educational efforts to legislative enactments. We examine the evidence used in ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：
更新日期：1988-05-01 00:00:00
abstract：:Liraglutide is a once-daily glucagon-like peptide-1 analogue being developed for the treatment of type 2 diabetes. The aim of this study was to investigate the effect of age and gender on the pharmacokinetics of liraglutide. Eight male and 8 female subjects were recruited from an 18- to 45-year-old group and an over-6...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1177/0091270006288215
更新日期：2006-06-01 00:00:00
abstract：:Relationships between tocilizumab exposure and response were evaluated using data from 4 phase III studies. Increased tocilizumab exposure was associated with improvements in Disease Activity Score using 28 joints (DAS28) and American College of Rheumatology (ACR) criteria and with a decrease in inflammation markers. ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1177/0091270012437585
更新日期：2013-02-01 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：:Amikacin was administered to 51 patients with serious Gram-negative infections. A favorable clinical outcome was observed in 32 patients (62 per cent). No major untoward effects were noted. The severity of the underlying disease and the site of the infection were important for the outcome. Urinary tract infections res...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1976.tb01520.x
更新日期：1976-04-01 00:00:00
abstract：:R(+)-alpha-lipoic acid is a natural occurring compound that acts as an essential cofactor for certain dehydrogenase complexes. The redox couple alpha-lipoic acid/dihydrolipoic acid possesses potent antioxidant activity. Exogenous racemic alpha-lipoic acid orally administered for the symptomatic treatment of diabetic p...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1177/0091270003258654
更新日期：2003-11-01 00:00:00
abstract：:Eleven subjects completed a clinical trial to determine the safety/tolerability of freeze-dried black raspberries (BRB) and to measure, in plasma and urine, specific anthocyanins-cyanidin-3-glucoside, cyanidin-3-sambubioside, cyanidin-3-rutinoside, and cyanidin-3-xylosylrutinoside, as well as ellagic acid. Subjects we...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1177/0091270005279636
更新日期：2005-10-01 00:00:00
abstract：:Reduced bioavailability (F) due to hepatic first-pass extraction of an oral dose (D) is a well-known pharmacokinetic phenomenon. An integrated solution for Michaelis-Menten kinetics of the first-pass effect is derived from the maximal metabolic rate (Vm), volume of distribution (Vd), first order absorption rate consta...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1989.tb03320.x
更新日期：1989-03-01 00:00:00
abstract：:The onset and offset of the electropharmacologic effect of procainamide was studied in nine patients with ventricular arrhythmias. Procainamide was given at a constant infusion rate of 0.27 +/- 0.05 mg/kg/min for 50 to 60 minutes to an average total dose of 15.5 +/- 4.4 mg/kg. The QRS interval (used as an index of ele...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1988.tb03118.x
更新日期：1988-11-01 00:00:00
abstract：:The effect of dose and gender on the pharmacokinetics (PK) and pharmacodynamics (PD) of zolpidem after administration of a buffered zolpidem sublingual tablet (ZST; Intermezzo®, Purdue Pharma L.P., Stamford, CT, USA) was evaluated in healthy non-elderly male and female volunteers. Subjects received a single morning do...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1002/jcph.220
更新日期：2014-03-01 00:00:00
abstract：:The benzothiadiazide diuretics are known to cause magnesium and potassium wasting and retention of calcium and uric acid. The effect of magnesium replacement on diuretic-induced changes in sodium, potassium, calcium, and magnesium balance, weight, and blood pressure was studied in 12 normal subjects and 13 hypertensiv...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1978.tb01582.x
更新日期：1978-11-01 00:00:00
abstract：:Acute asthma exacerbations are primarily due to airway inflammation and remain one of the most frequent reasons for childhood hospitalizations. Although systemic corticosteroids remain the mainstay of therapy because of their anti-inflammatory properties, not all inflammatory pathways are responsive to systemic cortic...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.1738
更新日期：2021-03-01 00:00:00
abstract：:Guanfacine, an alpha 2 adrenoceptor agonist, was compared with prazosin hydrochloride for the treatment of patients with mild to moderate essential hypertension in an 8-week, double-blind, randomized, parallel evaluation to determine efficacy and safety. The study consisted of a 2-week screening/weaning period (phase ...
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.1552-4604.1990.tb01849.x
更新日期：1990-12-01 00:00:00
abstract：:The steady-state pharmacokinetics of didanosine (DDI) and ketoconazole (KET) were evaluated when the agents were administered alone or concurrently to patients seropositive for the human immunodeficiency virus. Using a randomized, three-way crossover design, multiple oral doses of DDI (375 mg twice daily for 4 days), ...
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.tb01921.x
更新日期：1993-10-01 00:00:00
abstract：:The safety, tolerability, and pharmacokinetics of orally administered enzastaurin were evaluated in 2 placebo-controlled, dose escalation studies in healthy subjects. In the first human dose study, single doses (2-400 mg) were evaluated, with 22 subjects receiving enzastaurin. The mean half-lives of enzastaurin and it...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1177/0091270007304775
更新日期：2007-09-01 00:00:00
abstract：:This report briefly discusses some aspects of autonomic cardiovascular dysfunction as related to changes in orthostatic function in patients, bed rest subjects, and astronauts. This relationship is described in normal individuals to provide the basis for discussion of parameters that may be altered in patients, bed re...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1002/j.1552-4604.1993.tb01944.x
更新日期：1993-11-01 00:00:00
abstract：:The centrally acting agents are one of several differing classes of drugs now available for antihypertensive therapy. The availability of newer pharmacologic classes, including the beta-blockers, alpha-blockers. ACE inhibitors and calcium channel blockers, has resulted in a relative decline in the use of the centrally...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1002/j.1552-4604.1989.tb03387.x
更新日期：1989-07-01 00:00:00
abstract：:DS-1040, a low-molecular-weight imidazole derivative, inhibits the enzymatic activity of thrombin-activatable fibrinolysis inhibitor (TAFIa), enhancing endogenous tissue plasminogen activator-triggered fibrinolysis. This first-in-human, randomized, placebo-controlled, phase 1 study evaluated the safety, pharmacokineti...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1002/jcph.1474
更新日期：2019-12-01 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：:The hydrochlorothiazide component of Maxzide (Lederle Laboratories, Pearl River, NY) has been shown to be more bioavailable than the hydrochlorothiazide component of Dyazide (Smith, Kline and French Laboratories, Philadelphia, PA). The authors compared the antihypertensive effectiveness of a half-tablet of Maxzide (25...
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.1552-4604.1990.tb03632.x
更新日期：1990-08-01 00:00:00
abstract：:A clinical study was performed on 41 asthmatic patients. After complete physical and spirometric examinations, they received capsules containing 200 mg anhydrous theophylline per capsule t.i.d. for three weeks. All other antiasthmatic medications were omitted during this study. The results showed that these capsules (...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1976.tb01535.x
更新日期：1976-07-01 00:00:00
