We have located links that may give you full text access.
JOURNAL ARTICLE
RESEARCH SUPPORT, N.I.H., EXTRAMURAL
Plasma and cerebrospinal fluid pharmacokinetics of thalidomide and lenalidomide in nonhuman primates.
Cancer Chemotherapy and Pharmacology 2012 April
PURPOSE: Thalidomide, originally developed as a sedative, was subsequently identified to have antiangiogenic properties. Lenalidomide is an antiangiogenic and immunomodulatory agent that has been utilized in the treatment of patients with brain tumors. We studied the pharmacokinetics and cerebrospinal fluid (CSF) penetration of thalidomide and lenalidomide in a nonhuman primate model.
METHODS: A dose of 50 mg of thalidomide or 20 mg of lenalidomide was administered once orally to each of three rhesus monkeys. Plasma and CSF samples were obtained at specified intervals, and the thalidomide or lenalidomide concentrations were determined by high-performance liquid chromatography with tandem mass spectrometry. Pharmacokinetic parameters were estimated using noncompartmental methods. CSF penetration was calculated as area under the concentration-time curve (AUC) CSF/AUC plasma.
RESULTS: For thalidomide, the median apparent clearance (Cl/F) was 2.9 mL/min/kg, the median plasma AUC was 80 μM h, and the median terminal half-life (t(½)) was 13.3 h. For lenalidomide, the median Cl/F was 8.7 mL/min/kg, the median AUC was 9 μM h, and the median t(½) was 5.6 h. Thalidomide was detected in the CSF of all animals, with a median penetration of 42%. Lenalidomide was detected in the CSF of 2 of 3 animals, with a CSF penetration of 11% in each.
CONCLUSION: Thalidomide and lenalidomide penetrate into the CSF after oral administration of clinically relevant doses. Plasma exposure to lenalidomide was similar in our model to that observed in studies involving children who have brain tumors. These results support further development of lenalidomide for the treatment of central nervous system malignancies.
METHODS: A dose of 50 mg of thalidomide or 20 mg of lenalidomide was administered once orally to each of three rhesus monkeys. Plasma and CSF samples were obtained at specified intervals, and the thalidomide or lenalidomide concentrations were determined by high-performance liquid chromatography with tandem mass spectrometry. Pharmacokinetic parameters were estimated using noncompartmental methods. CSF penetration was calculated as area under the concentration-time curve (AUC) CSF/AUC plasma.
RESULTS: For thalidomide, the median apparent clearance (Cl/F) was 2.9 mL/min/kg, the median plasma AUC was 80 μM h, and the median terminal half-life (t(½)) was 13.3 h. For lenalidomide, the median Cl/F was 8.7 mL/min/kg, the median AUC was 9 μM h, and the median t(½) was 5.6 h. Thalidomide was detected in the CSF of all animals, with a median penetration of 42%. Lenalidomide was detected in the CSF of 2 of 3 animals, with a CSF penetration of 11% in each.
CONCLUSION: Thalidomide and lenalidomide penetrate into the CSF after oral administration of clinically relevant doses. Plasma exposure to lenalidomide was similar in our model to that observed in studies involving children who have brain tumors. These results support further development of lenalidomide for the treatment of central nervous system malignancies.
Full text links
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app