Richard Hajdu

TL;DR: It is shown that lymphocyte trafficking is altered by the lysophospholipid sphingosine-1-phosphate (S1P) and by a phosphoryl metabolites of the immunosuppressive agent FTY720.

TL;DR: The results with these Sphk1 null mice reveal that some key physiologic processes that require S1P receptor signaling, such as vascular development and proper lymphocyte distribution, can occur in the absence of SPHK1.

TL;DR: Three lines of evidence link S1P3 receptor activity with acute toxicity and cardiovascular regulation: compound potency on S 1P3 correlated with toxicity and bradycardia; the shift in potency of phosphorylated-FTY720 for inducing lymphopenia versus brady Cardia and hypertension was consistent with affinity for S1 p1 relative to S1p3; and toxicity, brady cardia, and hypertension were absent in S1 P3-/- mice.

TL;DR: The reduction in clearance of THM and MK0787 from plasma of rats and rabbits after ligation of renal arteries indicate that the kidneys are responsible for 35 and 92%, respectively, of metabolic drug clearance, and despite this unusual degree of metabolism localized in the kidney, the plasma half-life of MK 0787 and its efficacy against experimental systemic infections in animals remain satisfactory.

TL;DR: Single daily doses of MK-0991 should provide adequate systemic levels of fungicidal activity as a result of its long half-life pharmacokinetics, wide distribution, and slowly accumulating concentrations in tissue.