PMID- 22956478
OWN - NLM
STAT- MEDLINE
DCOM- 20130404
LR  - 20211021
IS  - 1550-7416 (Electronic)
IS  - 1550-7416 (Linking)
VI  - 14
IP  - 4
DP  - 2012 Dec
TI  - Pharmacokinetics and tissue disposition of lenalidomide in mice.
PG  - 872-82
LID - 10.1208/s12248-012-9401-2 [doi]
AB  - Lenalidomide is a synthetic derivative of thalidomide exhibiting multiple 
      immunomodulatory activities beneficial in the treatment of several hematological 
      malignancies. Murine pharmacokinetic characterization necessary for translational 
      and further preclinical investigations has not been published. Studies herein 
      define mouse plasma pharmacokinetics and tissue distribution after intravenous 
      (IV) bolus administration and bioavailability after oral and intraperitoneal 
      delivery. Range finding studies used lenalidomide concentrations up to 15 mg/kg 
      IV, 22.5 mg/kg intraperitoneal injections (IP), and 45 mg/kg oral gavage (PO). 
      Pharmacokinetic studies evaluated doses of 0.5, 1.5, 5, and 10 mg/kg IV and 0.5 
      and 10 mg/kg doses for IP and oral routes. Liquid chromatography-tandem mass 
      spectrometry was used to quantify lenalidomide in plasma, brain, lung, liver, 
      heart, kidney, spleen, and muscle. Pharmacokinetic parameters were estimated 
      using noncompartmental and compartmental methods. Doses of 15 mg/kg IV, 
      22.5 mg/kg IP, and 45 mg/kg PO lenalidomide caused no observable toxicity up to 
      24 h postdose. We observed dose-dependent kinetics over the evaluated dosing 
      range. Administration of 0.5 and 10 mg/kg resulted in systemic bioavailability 
      ranges of 90-105% and 60-75% via IP and oral routes, respectively. Lenalidomide 
      was detectable in the brain only after IV dosing of 5 and 10 mg/kg. 
      Dose-dependent distribution was also observed in some tissues. High oral 
      bioavailability of lenalidomide in mice is consistent with oral bioavailability 
      in humans. Atypical lenalidomide tissue distribution was observed in spleen and 
      brain. The observed dose-dependent pharmacokinetics should be taken into 
      consideration in translational and preclinical mouse studies.
FAU - Rozewski, Darlene M
AU  - Rozewski DM
AD  - Division of Pharmaceutics, College of Pharmacy, 230 Parks Hall, 500W. 12th 
      Avenue, Columbus, Ohio 43210, USA.
FAU - Herman, Sarah E M
AU  - Herman SE
FAU - Towns, William H 2nd
AU  - Towns WH 2nd
FAU - Mahoney, Emilia
AU  - Mahoney E
FAU - Stefanovski, Matthew R
AU  - Stefanovski MR
FAU - Shin, Jungook D
AU  - Shin JD
FAU - Yang, Xiaoxia
AU  - Yang X
FAU - Gao, Yue
AU  - Gao Y
FAU - Li, Xiaobai
AU  - Li X
FAU - Jarjoura, David
AU  - Jarjoura D
FAU - Byrd, John C
AU  - Byrd JC
FAU - Johnson, Amy J
AU  - Johnson AJ
FAU - Phelps, Mitch A
AU  - Phelps MA
LA  - eng
GR  - 5KL2RR025754/RR/NCRR NIH HHS/United States
GR  - K12CA133250/CA/NCI NIH HHS/United States
GR  - K12 CA133250/CA/NCI NIH HHS/United States
GR  - KL2 RR025754/RR/NCRR NIH HHS/United States
GR  - P50 CA140158/CA/NCI NIH HHS/United States
GR  - 1 P50 CA140158/CA/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120907
PL  - United States
TA  - AAPS J
JT  - The AAPS journal
JID - 101223209
RN  - 0 (Antineoplastic Agents)
RN  - 4Z8R6ORS6L (Thalidomide)
RN  - F0P408N6V4 (Lenalidomide)
SB  - IM
MH  - Administration, Oral
MH  - Animals
MH  - Antineoplastic Agents/administration & dosage/*pharmacokinetics
MH  - Biological Availability
MH  - Chromatography, Liquid
MH  - Dose-Response Relationship, Drug
MH  - Injections, Intraperitoneal
MH  - Injections, Intravenous
MH  - Lenalidomide
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Species Specificity
MH  - Tandem Mass Spectrometry
MH  - Thalidomide/administration & dosage/*analogs & derivatives/pharmacokinetics
MH  - Time Factors
MH  - Tissue Distribution
PMC - PMC3475844
EDAT- 2012/09/08 06:00
MHDA- 2013/04/05 06:00
PMCR- 2013/09/07
CRDT- 2012/09/08 06:00
PHST- 2011/12/30 00:00 [received]
PHST- 2012/08/08 00:00 [accepted]
PHST- 2012/09/08 06:00 [entrez]
PHST- 2012/09/08 06:00 [pubmed]
PHST- 2013/04/05 06:00 [medline]
PHST- 2013/09/07 00:00 [pmc-release]
AID - 9401 [pii]
AID - 10.1208/s12248-012-9401-2 [doi]
PST - ppublish
SO  - AAPS J. 2012 Dec;14(4):872-82. doi: 10.1208/s12248-012-9401-2. Epub 2012 Sep 7.