Pharmacokinetics of intravenous pan-class I phosphatidylinositol 3-kinase (PI3K) inhibitor [(14)C]copanlisib (BAY 80-6946) in a mass balance study in healthy male volunteers.

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Gerisch M, Schwarz T, Lang D, Rohde G, Reif S, Genvresse I, Reschke S, van der Mey D, Granvil C

Pharmacokinetics of intravenous pan-class I phosphatidylinositol 3-kinase (PI3K) inhibitor [(14)C]copanlisib (BAY 80-6946) in a mass balance study in healthy male volunteers.

Cancer Chemother Pharmacol. 2017 Sep;80(3):535-544. doi: 10.1007/s00280-017-3383-9. Epub 2017 Jul 11.

PubMed ID

28714036 [ View in PubMed

]

Abstract

PURPOSE: To determine the pharmacokinetics of radiolabeled copanlisib (BAY 80-6946) in healthy male volunteers and to investigate the disposition and biotransformation of copanlisib. METHODS: A single dose of 12 mg copanlisib containing 2.76 MBq [(14)C]copanlisib was administered as a 1-h intravenous infusion to 6 volunteers with subsequent sampling up to 34 days. Blood, plasma, urine and feces were collected to monitor total radioactivity, parent compound and metabolites. RESULTS: Copanlisib treatment was well tolerated. Copanlisib was rapidly distributed throughout the body with a volume distribution of 1870 L and an elimination half-life of 52.1-h (range 40.4-67.5-h). Copanlisib was the predominant component in human plasma (84% of total radioactivity AUC) and the morpholinone metabolite M1 was the only circulating metabolite (about 5%). Excretion of drug-derived radioactivity based on all 6 subjects was 86% of the dose within a collection interval of 20-34 days with 64% excreted into feces as major route of elimination and 22% into urine. Unchanged copanlisib was the main component excreted into urine (15% of dose) and feces (30% of dose). Excreted metabolites (41% of dose) of copanlisib resulted from oxidative biotransformation. CONCLUSIONS: Copanlisib was eliminated predominantly in the feces compared to urine as well as by hepatic biotransformation, suggesting that the clearance of copanlisib would more likely be affected by hepatic impairment than by renal dysfunction. The dual mode of elimination via unchanged excretion of copanlisib and oxidative metabolism decreases the risk of clinically relevant PK-related drug-drug interactions.

DrugBank Data that Cites this Article

Drugs

Copanlisib

Drug Reactions

Reaction
Copanlisib DB12483 Cytochrome P450 3A4 Copanlisib M1 metabolite DBMET03730	Details
Copanlisib DB12483 Cytochrome P450 3A4 Copanlisib M4 metabolite DBMET03731	Details
Copanlisib DB12483 Cytochrome P450 3A4 Copanlisib M3 metabolite DBMET03732	Details
Copanlisib DB12483 Cytochrome P450 3A4 Copanlisib M21 metabolite DBMET03733	Details
Copanlisib DB12483 Cytochrome P450 3A4 Copanlisib M15 metabolite DBMET03734 Copanlisib M2 metabolite DBMET03735	Details

Drug Interactions

Drugs	Interaction
Integrate drug-drug interactions in your software
Copanlisib Nelfinavir	The metabolism of Copanlisib can be decreased when combined with Nelfinavir.
Copanlisib Ketoconazole	The metabolism of Copanlisib can be decreased when combined with Ketoconazole.
Copanlisib Itraconazole	The metabolism of Copanlisib can be decreased when combined with Itraconazole.
Copanlisib Clarithromycin	The metabolism of Copanlisib can be decreased when combined with Clarithromycin.
Copanlisib Boceprevir	The metabolism of Copanlisib can be decreased when combined with Boceprevir.