No clinically significant drug interactions between lenalidomide and Pglycoprotein substrates and inhibitors: results from controlled phase I studies in healthy volunteers.
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Chen N, Weiss D, Reyes J, Liu L, Kasserra C, Wang X, Zhou S, Kumar G, Weiss L, Palmisano M
No clinically significant drug interactions between lenalidomide and Pglycoprotein substrates and inhibitors: results from controlled phase I studies in healthy volunteers.
Cancer Chemother Pharmacol. 2014 May;73(5):1031-9. doi: 10.1007/s00280-014-2438-4.
- PubMed ID
- 24659021 [ View in PubMed]
- Abstract
PURPOSE: Lenalidomide, a weak substrate of P-glycoprotein (P-gp) in vitro, is an oral anticancer drug eliminated predominantly via renal excretion as unchanged compound. The role of P-gp in lenalidomide disposition and the associated clinical relevance were evaluated. METHODS: Two phase I, crossover studies were conducted in healthy volunteers. In Study 1, subjects received lenalidomide (10 mg x 7 days) alone or with the P-gp substrate digoxin (0.5 mg on Day 5). In Study 2, subjects received lenalidomide (a single 25 mg dose) alone, the P-gp inhibitor quinidine (300-600 mg twice-daily x 5 days) plus lenalidomide (on Day 4), the P-gp inhibitor/substrate temsirolimus (a single 25 mg dose) alone, or lenalidomide plus temsirolimus. Pharmacokinetic and safety data were collected for lenalidomide and the co-administrated drugs. RESULTS: There were no significant changes in the maximum concentration (C max) and area under the plasma concentration-time curve (AUC) of lenalidomide when co-administered with quinidine, digoxin, or temsirolimus. Neither the rate nor the capacity of lenalidomide renal excretion was affected by quinidine or temsirolimus, in addition lenalidomide absorption rate and bioavailability remained unchanged. Furthermore, lenalidomide had no significant effect on blood C max and AUC of temsirolimus and its active metabolite sirolimus (also a P-gp inhibitor/substrate). The C max of digoxin was slightly higher (+14 %) when administered with lenalidomide versus placebo. There were no other changes in digoxin pharmacokinetics upon co-administration with lenalidomide. No remarkable safety findings were observed. CONCLUSIONS: There are no clinically significant pharmacokinetic interactions between lenalidomide and substrates or inhibitors of P-gp.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Lenalidomide P-glycoprotein 1 Protein Humans NoSubstrateDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareDigoxinLenalidomide The serum concentration of Digoxin can be increased when it is combined with Lenalidomide.