title: No clinically significant drug interactions between lenalidomide  and P‑glycoprotein substrates and inhibitors: results  from controlled phase I studies in healthy volunteers.
abstract: OBJECTIVE
  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 × 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 × 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.
authors.forename: Nianhang
authors.initials: N
authors.lastname: Chen
authors.forename: Daniel
authors.initials: D
authors.lastname: Weiss
authors.forename: Josephine
authors.initials: J
authors.lastname: Reyes
authors.forename: Liangang
authors.initials: L
authors.lastname: Liu
authors.forename: Claudia
authors.initials: C
authors.lastname: Kasserra
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Wang
authors.forename: Simon
authors.initials: S
authors.lastname: Zhou
authors.forename: Gondi
authors.initials: G
authors.lastname: Kumar
authors.forename: Lilia
authors.initials: L
authors.lastname: Weiss
authors.forename: Maria
authors.initials: M
authors.lastname: Palmisano
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D000293:Adolescent; D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020533:Angiogenesis Inhibitors; D013792:Thalidomide; D000077269:Lenalidomide