Clinical Pharmacokinetics and Pharmacodynamics of Nintedanib.
Article Details
- CitationCopy to clipboard
Wind S, Schmid U, Freiwald M, Marzin K, Lotz R, Ebner T, Stopfer P, Dallinger C
Clinical Pharmacokinetics and Pharmacodynamics of Nintedanib.
Clin Pharmacokinet. 2019 Sep;58(9):1131-1147. doi: 10.1007/s40262-019-00766-0.
- PubMed ID
- 31016670 [ View in PubMed]
- Abstract
Nintedanib is an oral, small-molecule tyrosine kinase inhibitor approved for the treatment of idiopathic pulmonary fibrosis and patients with advanced non-small cell cancer of adenocarcinoma tumour histology. Nintedanib competitively binds to the kinase domains of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF). Studies in healthy volunteers and in patients with advanced cancer have shown that nintedanib has time-independent pharmacokinetic characteristics. Maximum plasma concentrations of nintedanib are reached approximately 2-4 h after oral administration and thereafter decline at least bi-exponentially. Over the investigated dose range of 50-450 mg once daily and 150-300 mg twice daily, nintedanib exposure increases are dose proportional. Nintedanib is metabolised via hydrolytic ester cleavage, resulting in the formation of the free acid moiety that is subsequently glucuronidated and excreted in the faeces. Less than 1% of drug-related radioactivity is eliminated in urine. The terminal elimination half-life of nintedanib is about 10-15 h. Accumulation after repeated twice-daily dosing is negligible. Sex and renal function have no influence on nintedanib pharmacokinetics, while effects of ethnicity, low body weight, older age and smoking are within the inter-patient variability range of nintedanib exposure and no dose adjustments are required. Administration of nintedanib in patients with moderate or severe hepatic impairment is not recommended, and patients with mild hepatic impairment should be monitored closely and the dose adjusted accordingly. Nintedanib has a low potential for drug-drug interactions, especially with drugs metabolised by cytochrome P450 enzymes. Concomitant treatment with potent inhibitors or inducers of the P-glycoprotein transporter can affect the pharmacokinetics of nintedanib. At an investigated dose of 200 mg twice daily, nintedanib does not have proarrhythmic potential.
DrugBank Data that Cites this Article
- Drugs
- Drug Targets
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Nintedanib Cytochrome P450 3A4 Protein Humans NoSubstrateDetails Nintedanib UDP-glucuronosyltransferase 1-1 Protein Humans UnknownSubstrateDetails Nintedanib UDP-glucuronosyltransferase 1-10 Protein Humans UnknownSubstrateDetails Nintedanib UDP-glucuronosyltransferase 1-7 Protein Humans UnknownSubstrateDetails Nintedanib UDP-glucuronosyltransferase 1-8 Protein Humans UnknownSubstrateDetails - Drug Carriers
Drug Carrier Kind Organism Pharmacological Action Actions Nintedanib Serum albumin Protein Humans UnknownSubstrateDetails - Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Nintedanib ATP-binding cassette sub-family G member 2 Protein Humans UnknownNot Available Details Nintedanib P-glycoprotein 1 Protein Humans NoSubstrateInhibitorDetails Nintedanib Solute carrier family 22 member 1 Protein Humans UnknownSubstrateInhibitorDetails - Drug Reactions
Reaction Details Details - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareAbciximabNintedanib The risk or severity of bleeding can be increased when Nintedanib is combined with Abciximab. AcenocoumarolNintedanib The risk or severity of bleeding can be increased when Nintedanib is combined with Acenocoumarol. AlteplaseNintedanib The risk or severity of bleeding can be increased when Nintedanib is combined with Alteplase. AncrodNintedanib The risk or severity of bleeding can be increased when Nintedanib is combined with Ancrod. AnistreplaseNintedanib The risk or severity of bleeding can be increased when Nintedanib is combined with Anistreplase.
