No Effect of Levothyroxine and Levothyroxine-Induced Subclinical Thyrotoxicosis on the Pharmacokinetics of Sorafenib in Healthy Male Subjects.

Background: Patients receiving the multikinase inhibitor sorafenib for locally recurrent or metastatic, progressive, differentiated thyroid carcinoma (DTC) refractory to radioactive iodine often receive concomitant levothyroxine for thyrotropin (TSH) suppression. In the Phase 3 DTC trial (DECISION), sorafenib exposure was approximately twofold higher than that observed in other cancers. This study assessed sorafenib pharmacokinetics without and with concomitant levothyroxine to examine whether a levothyroxine interaction or levothyroxine-induced subclinical thyrotoxicosis results in increased sorafenib exposure in patients with DTC.

Renal excretion of clofarabine: assessment of dose-linearity and role of renal transport systems on drug excretion.

The renal excretion of clofarabine was studied in vitro in the isolated perfused rat kidney (IPK) model and in vivo in rats. Clofarabine excretion was studied at four doses (160, 800, 2000 and 4000microg) in the IPK, targeting perfusate levels of 2, 10, 25, 50microg/mL, respectively. Clofarabine (2microg/mL) was also co-perfused with known inhibitors of the, organic cation (cimetidine, ranitidine and tyramine) and organic anion (probenecid, ellagic acid) transport systems.

Molecular alignment of rigid rods in nonrigid spherical pores.

We have investigated the orientation ordering of two shish-kebab chains confined by spherically harmonic potentials through Monte Carlo simulations and asymptotic analysis. The rigid rod is modeled as shish-kebab chains consisting of tangent hard spheres aligned in the same axis, and the harmonic potential is chosen to model nonrigid cavities. We first show that the interactions between a rod and the spherically harmonic potential are independent of chain orientation, indicating that the alignment of two confined rods arises from the excluded volume interactions alone.