Abstract：
:Nintedanib is an intracellular inhibitor of tyrosine kinases used in the treatment of non-small cell lung cancer and idiopathic pulmonary fibrosis (IPF). This phase 1 open-label study investigated the influence of mild and moderate hepatic impairment on the pharmacokinetics (PK), safety, and tolerability of nintedanib following oral administration of a single 100-mg dose. Subjects with hepatic impairment classified as Child-Pugh A (mild hepatic impairment) or Child-Pugh B (moderate hepatic impairment) were eligible. The control group comprised healthy matched subjects. Primary end points were Cmax and AUC0-∞ of nintedanib. Thirty-three subjects received nintedanib (8 in each of the Child-Pugh A and Child-Pugh B groups and 17 controls). The shape of the plasma concentration-time curve for nintedanib was similar between Child-Pugh A or B and healthy subjects. Nintedanib exposure was ∼2-fold higher in Child-Pugh A subjects and ∼8-fold higher in Child-Pugh B subjects than in healthy subjects. Adverse events were reported in 3 Child-Pugh B subjects (37.5%), no Child-Pugh A subjects, and 3 healthy subjects (17.6%). In conclusion, exposure to nintedanib was higher in Child-Pugh A and B subjects than in matched healthy subjects. A single dose of nintedanib 100 mg had an acceptable safety and tolerability profile in subjects with hepatic impairment. Results of this dedicated phase 1 study are in line with exploratory investigations into the PK of nintedanib in patients with advanced solid tumors or IPF and hepatic impairment.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Marzin K,Kretschmar G,Luedtke D,Kraemer S,Kuelzer R,Schlenker-Herceg R,Schmid U,Schnell D,Dallinger Cdoi
10.1002/jcph.1025subject
Has Abstractpub_date
2018-03-01 00:00:00pages
357-363issue
3eissn
0091-2700issn
1552-4604journal_volume
58pub_type
杂志文章abstract：:Suvorexant is an orexin receptor antagonist for treating insomnia. The maximum approved dose in the United States and Japan is 20 mg. We evaluated suvorexant effects on respiration during sleep in a randomized, double-blind, 3-period crossover study of healthy adult men (n = 8) and women (n = 4) ≤ 50 years old who rec...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1002/jcph.523
更新日期：2015-10-01 00:00:00
abstract：:This study aimed to investigate a food effect on the bio-availability of modified-release (MR) trimetazidine tablets in 36 healthy volunteers. Trimetazidine, an anti-ischemic drug, protects the myocardial cell from the harmful effects of ischemia. The authors investigated the effect of being under a fasting or fed sta...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1177/0091270011422813
更新日期：2012-10-01 00:00:00
abstract：:We aim to evaluate the influence of covariates, including cytochrome P450 3A (CYP3A) genetic polymorphisms, on the pharmacokinetics of midazolam (MDZ) in Asian cancer patients, using a population pharmacokinetic approach. Pharmacokinetic data were obtained from 24 adult cancer patients who received an intravenous bolu...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/jcph.230
更新日期：2014-02-01 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：:The relative analgesic potency of oral and intramuscular oxymorphone was evaluated in a double-blind crossover comparison of graded single doses in patients with chronic pain due to cancer. When both duration and intensity of analgesia are considered (total effect), oral oxymorphone was 1/6 as potent as the intramuscu...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1177/009127007701700402
更新日期：1977-04-01 00:00:00
abstract：:The alpha 1-adrenoceptor antagonists doxazosin and terazosin and the 5 alpha-reductase inhibitor finasteride are used in the treatment of benign prostatic hyperplasia. The aim of this study was to assess the potential pharmacokinetic interaction of doxazosin or terazosin when coadministered with finasteride. This was ...
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：10.1177/009127009803801113
更新日期：1998-11-01 00:00:00
abstract：:Current guidelines for hypercholesterolemia treatment emphasize lifestyle modification and lipid-modifying therapy to reduce the risk for cardiovascular disease. Statins are the primary class of agents used for the treatment of hypercholesterolemia. Although statins are effective for many patients, they fail to achiev...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1002/jcph.766
更新日期：2017-01-01 00:00:00
abstract：:The decrease in renal blood flow (RBF) observed in patients with hypertension can be increased with converting enzyme inhibition (CEI). It is unknown whether the decrease in RBF observed with age can also be increased with CEI. This study compared the short- and long-term effects of captopril monotherapy in young (les...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1991.tb01888.x
更新日期：1991-01-01 00:00:00
abstract：:A total of 175 physicians were surveyed by questionnaire before a Clinical Pharmacology Consult Service was started. Of those that responded, 72% thought the service would be helpful, although 40% said they would use the service no more than once a month. Most physicians (75%) preferred self-initiated consultations to...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1988.tb03096.x
更新日期：1988-01-01 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：: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：:A decrease in dietary protein intake lowers the clearance of a number of substances excreted principally by the kidney including uric acid and oxypurinol, the major metabolite of allopurinol. We studied the kinetics of uric acid and oxypurinol in seven healthy volunteers on a normal protein diet (2600 calories; 100 g ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1989.tb03239.x
更新日期：1989-01-01 00:00:00
abstract：:A novel, nonscrotal, transdermal delivery system for testosterone therapy has been marketed for treatment of hypogonadal men. The usual dose of this system is two 2.5 mg/day systems applied daily. A new system has been developed that administers a dose of 5 mg/day using a single patch rather than two patches. A random...
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.tb04377.x
更新日期：1998-01-01 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：:The pharmacokinetics of exogenously administered DHEA have not been well characterized despite its increasing use in therapeutic and research investigations. The purpose of this study was to evaluate the pharmacokinetics of DHEA and its sulfated metabolite (DHEA-S) after single- and multiple-dose oral administration o...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：
更新日期：2000-06-01 00:00:00
abstract：:Golimumab is a fully human antitumor necrosis factor alpha (TNF-alpha) monoclonal antibody that is being developed for intravenous and subcutaneous administration. To assess the pharmacokinetics and safety of the intravenous formulation of golimumab, 36 adult subjects with rheumatoid arthritis were randomly assigned t...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1177/0091270006298188
更新日期：2007-03-01 00:00:00
abstract：:The clinical effects of a cardioselective beta-adrenergic blocking drug, acebutolol, were studied in 25 patients with chronic stable angina, using a seven-week single-blind placebo leads to acebutolol (mean dose 913 mg/day) phase followed by 12-week randomized double-blind placebo leads to acebutolol (mean dose 968 mg...
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.1552-4604.1982.tb02688.x
更新日期：1982-08-01 00:00:00
abstract：:Aminoglycosides have become an indispensable component in the armamentarium against serious gram-negative infections. In spite of the availability of effective guidelines for prevention, the frequency of toxic side effects associated with aminoglycoside therapy is an impetus for the substitution of safer and equally e...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1002/j.1552-4604.1988.tb03109.x
更新日期：1988-10-01 00:00:00
abstract：:The efficacy and safety of esmolol, a titratable intravenous beta-adrenergic blocking agent with a short elimination half-life (t 1/2 = 9.0 min) was evaluated in a multicenter open-label study for the treatment of supraventricular tachyarrhythmias (heart rate greater than 100 bpm). The study also investigated the feas...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1988.tb03209.x
更新日期：1988-08-01 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：:Twenty young (45 years or younger) and 20 older (55 years or older) adult patients with mild hypertension were enrolled in this study to compare the hemodynamic effects of labetalol versus placebo in two age groups. Ten patients in each group were randomly assigned to receive either a single oral dose of labetalol (20...
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.tb03153.x
更新日期：1988-04-01 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：: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：: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：:The objective of the current study was to develop a population pharmacokinetics (PK) model for erythropoietin (Epo) in premature infants and healthy adults to characterize the variation in PK, and to study the differences in Epo PK in these 2 populations. Thirteen very low-birth-weight premature infants (<1500 g at bi...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.1368
更新日期：2019-06-01 00:00:00
abstract：:The time course, dose frequency schedule, and dose-response relationship of the citraturic response to orally administered potassium citrate was examined in 22 normal volunteers and 21 patients with uric acid or calcium nephrolithiasis. The slow-release (wax matrix) preparation of potassium citrate produced a rapid an...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1984.tb01809.x
更新日期：1984-01-01 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：: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 most commonly used Parkinson's disease (PD) treatment is the replacement of dopamine by its levodopa precursor (l-dopa). Monoamine oxidase-B (MAO-B) and catechol-o-methyl transferase (COMT) are enzymes involved in the metabolism and regulation of dopamine availability. In our study we investigated the possible rel...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.1096
更新日期：2018-07-01 00:00:00
abstract：:MC4-NN2-0453 is a novel, long-acting, selective, melanocortin-4-receptor agonist developed for treatment of obesity. This first-human-dose, randomized, double-blind, placebo-controlled trial investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of MC4-NN2-0453 in ov...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1002/jcph.211
更新日期：2014-04-01 00:00:00
