Steven K Teo

..The major route of thalidomide breakdown in humans and animals is through spontaneous hydrolysis with subsequent elimination in the urine...

..The analogue lenalidomide has shown potential in treating the bone marrow disorders multiple myeloma and myelodysplastic syndrome, and is presently in Phase II and III trials, respectively...

..No gross external changes were observed in F1 and F2 pups...

..Since thalidomide is mainly hydrolysed and passively excreted, its pharmacokinetics are not expected to change in patients with impaired liver or kidney function...

..The present work was performed to determine the effect of thalidomide exposure on reproductive function and early embryonic development...

..The developmental toxicity of both compounds was determined and compared in rats and rabbits according to current International Conference on Harmonization (ICH) guidelines...

..There were no abnormal clinical pathology or macroscopic or microscopic findings. Based on body weight changes, the no-observed-adverse-effect level (NOAEL) of d-MPH in beagle dogs was 3 mg/kg/day...

..Our present results along with published epidemiological data from patient populations are consistent with the conclusion that D-MPH and D,L-MPH do not present a carcinogenic risk to humans...

..In this article we report on the rapid racemization of the S-isomer of CC-4047 in human plasma and phosphate-buffered saline. These results support the further development of the racemate instead of the S-isomer...

..In summary, fewer significant FOBs were seen with D- and L-MPH compared to equimolar doses of D,L-MPH. L-MPH was the least potent in producing FOBs. These results were supported by rota-rod studies...

..Thalidomide has been used to treat ENL since the 1960s. One of its mechanisms of action is anti-inflammatory through selective inhibition of the pro-inflammatory cytokine TNF-alpha produced by monocytes...

..Overall, the toxicity profile observed in rats with 50 mg/kg per day D-MPH was comparable to that of an equimolar dose of D,L-MPH (100 mg/kg per day) when given repeatedly for 90 days using a twice a day dosing regimen...

..Neither compound produced any other significant adverse findings in F0 and F1 generation rats at doses that were at least 25 times the maximum daily human therapeutic dose...

..Batch sizes of 100 samples per matrix were analyzed with a total run time of 5 h. The methods successfully determined concentrations of thalidomide from a clinical study to levels as low as 7 ng/ml plasma and 8 ng/g semen, respectively...

..Semen levels could be significantly greater for therapeutic doses of more than 100 mg/day. Since the threshold dose for birth defects and thalidomide exposure is not known, male patients are advised to use barrier contraception...

..There was no gross and histopathologic evidence of any tumors. In summary, thalidomide at up to 1000 mg/kg/day for 53 weeks did not induce any major systemic toxicity or tumors in dogs. The NOAEL was 200 mg/kg/day...

..5-1.5 h, but had little effect on the extent of absorption from the Celgene capsule. Under fasted conditions, the Celgene thalidomide resulted in a two-fold greater C(max) and 10% greater AUC(0-infinity) than the Serral formulation...

..It also did not produce any significant increase in the average mutant frequencies of AS52 cells and mouse micronucleated polychromatic erythrocytes. We conclude that Celgene's Thalomid thalidomide is non-genotoxic...

..It is currently in phase II and III trials for these diseases respectively with numerous phase II trials in other hematologic and solid tumors...