Advertisement

Topics

Effect of hepatic or renal impairment on the pharmacokinetics of casopitant, a NK-1 receptor antagonist.

Summary of "Effect of hepatic or renal impairment on the pharmacokinetics of casopitant, a NK-1 receptor antagonist."

Two studies were conducted in subjects with mild or moderate hepatic or renal impairment and subjects with normal organ function to evaluate the pharmacokinetics of casopitant and to assess its safety in these populations. A total of 26 subjects were enrolled in the hepatic impairment study and 18 subjects in the renal impairment study. All subjects received oral casopitant 100 mg once-daily for 5 days. Casopitant area under the concentration-time curve (AUC) increased 11% and 24% in subjects with mild or moderate hepatic impairment, respectively, on Day 1, compared with subjects with normal hepatic function; a similar increase was observed on Day 5. The AUC of the active major metabolite, GSK525060, was reduced 29% and 19% on Days 1 and 5, respectively, in subjects with moderate hepatic impairment, but not altered by mild hepatic impairment. Casopitant AUC increased 34% and 22% on Day 1 in subjects with mild or moderate renal impairment, respectively, and 28% and 11% on Day 5, respectively, compared with subjects with normal renal function. GSK525060 AUC was increased 17% and 24% on Days 1 and 5, respectively, in subjects with mild renal impairment; but did not significantly change in subjects with moderate renal impairment. Further age-adjusted analysis showed no meaningful effect of renal impairment on casopitant or GSK525060 AUC. Plasma protein binding of casopitant and GSK525060 was similar in all subjects. The pharmacokinetics of casopitant is not altered to a clinically significant extent in subjects with mild or moderate, hepatic or renal impairment. The impact of severe hepatic or renal impairment was not evaluated.

Affiliation

Discovery Operations & Clinical Sciences, GlaxoSmithKline, Inc., Research Triangle Park, NC, USA, John.W.Bauman@gsk.com.

Journal Details

This article was published in the following journal.

Name: Investigational new drugs
ISSN: 1573-0646
Pages:

Links

DeepDyve research library

PubMed Articles [23880 Associated PubMed Articles listed on BioPortfolio]

Assessment of Hepatic Impairment and Implications for Pharmacokinetics of Substance Use Treatment.

Although the liver is the primary site of metabolism and biliary excretion for many medications, data are limited on the liver's pharmacokinetic abilities in cirrhosis. Cirrhosis develops through coll...

Pharmacokinetics of a Single Oral Dose of the MEK1/2 Inhibitor Selumetinib in Subjects With End-Stage Renal Disease or Varying Degrees of Hepatic Impairment Compared With Healthy Subjects.

Two phase I open-label studies were conducted to investigate the pharmacokinetics (PK), safety, and tolerability of single oral doses of selumetinib in subjects with end-stage renal disease (ESRD) und...

Erratum to: Clinical Pharmacokinetics of Sacubitril/Valsartan (LCZ696): A Novel Angiotensin Receptor-Neprilysin Inhibitor.

Sacubitril/valsartan (LCZ696) is indicated for the treatment of heart failure with reduced ejection fraction. Absorption of sacubitril/valsartan and conversion of sacubitril (prodrug) to sacubitrilat ...

Effects of Renal Function on Crizotinib Pharmacokinetics: Dose Recommendations for Patients with ALK-Positive Non-Small Cell Lung Cancer.

Crizotinib (250 mg twice daily) is the first anaplastic lymphoma kinase (ALK) inhibitor approved for treatment of ALK-positive non-small-cell lung cancer (NSCLC). The objectives of the current study ...

A novel and selective melanin-concentrating hormone receptor 1 antagonist ameliorates obesity and hepatic steatosis in diet-induced obese rodent models.

Melanin-concentrating hormone (MCH), a cyclic neuropeptide expressed predominantly in the lateral hypothalamus, plays an important role in the control of feeding behavior and energy homeostasis. Mice ...

Clinical Trials [9687 Associated Clinical Trials listed on BioPortfolio]

A Study to Evaluate the Pharmacokinetics of VI-0521 Subjects With Renal Impairment

VI-0521, a fixed dose combination of immediate-release (IR) phentermine and controlled-release (CR) topiramate, is in Phase III clinical development as a potential therapy for obesity. In ...

The Study of Effect of Hepatic Impairment on the Pharmacokinetics of Alectinib

This is a multicenter, non-randomized, single-dose, open-label study conducted in male and surgically sterile or post-menopausal female participants with stable chronic hepatic impairment ...

A Study to Assess the Effect of Hepatic Impairment on Safinamide Pharmacokinetics

The primary purpose of this study is to investigate the pharmacokinetics (behavior of the compound in the body) of safinamide in patients with different degrees of hepatic (liver) impairme...

Effect of Hepatic and Renal Impairment on the Pharmacokinetics, Safety and Tolerability of BAY1841788 (ODM-201)

Evaluate the potential effect of hepatic or renal impairment on the pharmacokinetics, safety and tolerability of BAY 1841788 (ODM-201).

TMC435-TiDP16-C113: A Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics of TMC435

The purpose of the study is to investigate the effect of moderate and severe hepatic impairment on the pharmacokinetics of TMC435. Pharmacokinetics means how the drug is absorbed into the ...

Medical and Biotech [MESH] Definitions

A thiazole derivative and atypical ANTIPSYCHOTIC AGENT that functions as a DOPAMINE D2 RECEPTOR ANTAGONIST; SEROTONIN 5-HT2 RECEPTOR ANTAGONIST, serotonin 5-HT7 receptor antagonist, and antagonist of the adrenergic α2A and α2C receptors, as well as a partial SEROTONIN 5-HT1A RECEPTOR AGONIST. It is used in the treatment of SCHIZOPHRENIA and BIPOLAR DISORDER.

A competitive histamine H2-receptor antagonist. Its main pharmacodynamic effect is the inhibition of gastric secretion.

A benzisoxazole derivative and active metabolite of RISPERIDONE that functions as a DOPAMINE D2 RECEPTOR ANTAGONIST and SEROTONIN 5-HT2 RECEPTOR ANTAGONIST. It is an ANTIPSYCHOTIC AGENT used in the treatment of SCHIZOPHRENIA.

An antagonist of ANGIOTENSIN TYPE 1 RECEPTOR with antihypertensive activity due to the reduced pressor effect of ANGIOTENSIN II.

The prototypical uricosuric agent. It inhibits the renal excretion of organic anions and reduces tubular reabsorption of urate. Probenecid has also been used to treat patients with renal impairment, and, because it reduces the renal tubular excretion of other drugs, has been used as an adjunct to antibacterial therapy.

Quick Search
Advertisement
 


DeepDyve research library

Relevant Topics

Hepatology
Hepatology is the study of liver, gallbladder, biliary tree, and pancreas, and diseases associated with them. This includes viral hepatitis, alcohol damage, cirrhosis and cancer. As modern lifestyles change, with alcoholism and cancer becoming more promi...

Nephrology - kidney function
Nephrology is a specialty of medicine and pediatrics that concerns itself with the study of normal kidney function, kidney problems, the treatment of kidney problems and renal replacement therapy (dialysis and kidney transplantation). Systemic conditions...


Searches Linking to this Article