Thalidomide pharmacokinetics

Eriksson, T., Bjorkman, S., Roth, B., and Hoglund, P., Intravenous formulations of the enantiomers of thalidomide pharmacokinetic and initial pharmacodynamic characterization in man, /. Pharm. Pharmacol., 52, 807-817, 2000. 

Lenalidomide was approved recently for the indication of myelodysplastic syndrome where the 5q deletion is present. Since lenalidomide is an analog of thalidomide, all the same precautions must be taken to prevent phocomelia. The time to maximum lenalidomide concentrations occurs 0.5 to 4 hours after the dose. The terminal half-life ranges from 3 to 9 hours. Approximately 65% of lenalidomide is eliminated unchanged in the urine, with clearance exceeding the glomerular filtration rate. To date, no pharmacokinetic studies have been done in patients with renal dysfunction. Lenalidomide is used in the treatment of myelodysplastic syndrome and multiple myeloma. Other side effects are neutropenia, thrombocytopenia, deep vein thrombosis, and pulmonary embolus. 

Tommy Eriksson, Sven Bjorkman, Bodil Roth, Asa Fyge, Peter Hoglund Stereospecific Determination, Chiral Inversion in vitro and Pharmacokinetics in Humans of the Enantiomers of Thalidomide, Chirality 7,44-52 (1995)... 

Eriksson T, Hoglund P, Turesson I, Waage A, Don BR, Vu J, Scheffler M, Kaysen GA. Pharmacokinetics of thalidomide in patients with impaired renal function and while on and off dialysis. J Pharm Pharmacol 2003 55(12) 1701-6. 

Trapnell CB, Donahue SR, Collins JM, Flockhart DA, Thacker D, Abernethy DR. Thalidomide does not alter the pharmacokinetics of ethinyl estradiol and norethin-drone. Clin Pharmacol Ther 1998 64(6) 597-602. 

The mechanism of the species-specific action of thalidomide is not known. The compound crosses the placenta and has similar pharmacokinetic parameters in susceptible species (rabbit) and resistant species (rodent). The molecular structure of thalidomide and requirements for malformation are very specific. Thalidomide decomposes rapidly in water to at least 12 different products - all of which are inactive as teratogens and all of which undergo biotransformation in vivo to other products. These data... 

Fyge, A., Hoglund, P. Stereospecific determination, chiral inversion in vitro and pharmacokinetics in humans of the enantiomers of thalidomide. Chirality, 1995, 7, 44-52. 

T. Eriksson, S. Bjorkman, B. Roth, A. Fyge, P. Hoglund, Stereospecific determination, chiral inversion in vitro and pharmacokinetics in humans of the enantiomers of thalidomide, Chirality 7 (1995) 44-52. T. Eriksson, S. Bjorkman, B. Roth, A. Fyge, P. Hoglund, Enantiomers of thalidomide Blood distribution and the influence of serum albumin on chiral inversion and hydrolysis. Chirality 10 (1998) 223-228. 

Schmahl, H.-J. Nau, H. Neubert, D. The enantiomers of the teratogenic thalidomide analogue EM 12 1. Chiral inversion and plasma pharmacokinetics in the marmoset monkey. Arch. Toxicol. 1988, 62, 200-204. 

Allegrini G, Di Paolo A, Cerri E, Cupini S, Amatori F, Masi G, Danesi R, Marcucci L, Bocci G, Del Tacca M, Falcone A. Irinotecan in combination witii thalidomide in patients widi advanced solid tumors a clinical study with pharmacod3mamic and pharmacokinetic evaluation. 

Rifampicin and phenobarbitai did not appear to alter thalidomide clearance in one study. Thalidomide increases the effect of other CNS depressants, and its CNS depressant activity is reduced by CNS stimulants. Thalidomide does not alter the pharmacokinetics of oral contraceptive steroids. 

Teo SK, Colburn WA, Tracewell WG, Kock KA, Stirling DI, Jaworsky MS, Scheffler Thcmas SD, Laskin OL. Clinical pharmacokinetics of thalidomide. CUn Pharmacokinet (200 43,311-27. 

Scheffler MR, Colburn W, Kook KA, Thomas SD. Thalidomide does not alter estrc en-pro-gesterone hormone single-dose pharmacokinetics. Clin Pharmacol Ther (1999) 65,483-. ... 

In a study intravenous zoledronic acid 4 mg every 4 weeks with alternate day prednisolone was given with or without thalidomide 200 mg daily for up to 1 year. The zoledronic acid pharmacokinetics were not affected by thalidomide and based on renal function no clinically adverse interaction occurred during concurrent use. The subjects in this study were patients with multiple myeloma with no disease progression 6 weeks after autologous stem-cell transplantation and conditioning with melphalan. ... 

Nakamura K, Matsuzawa N, Ohmori S, Ando Y, Yamazaki H, MatsunagaT (2013) Clinical evidence of pharmacokinetic changes in thalidomide therapy. Drug Metab Pharmacokinet 28 38 3... 

Chirality of pharmaceutical products is an important issue related to effective and safe therapy. Already more than 100 years ago, Louis Pasteur noticed the differences in the activity of compounds of natural origin [1], The tragedy of thalidomide and development of stereospecific analytical techniques resulted in broadening of studies on drug quality and inclusion of monitoring of biological activity and pharmacokinetics of stereoisomers. 

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