A phase 2 clinical trial of luspatercept in non-transfusion-dependent patients with myelodysplastic syndromes.

Luspatercept has shown durable clinical efficacy for the treatment of anemia in transfusion-dependent patients with lower-risk myelodysplastic syndromes (LR-MDS). We report the results of a prespecified primary analysis of a phase 2 trial of luspatercept in non-transfusion-dependent (NTD) Japanese patients with anemia due to LR-MDS. Luspatercept (starting dose 1.

Population pharmacokinetics of olprinone in healthy male volunteers.

Background: Olprinone decreases the cardiac preload and/or afterload because of its vasodilatory effect and increases myocardial contractility by inhibiting phosphodiesterase III.

Purpose: The objective of this study was to characterize the population pharmacokinetics of olprinone after a single continuous infusion in healthy male volunteers.

Methods: We used 500 plasma concentration data points collected from nine healthy male volunteers for the study.

Pharmacokinetics and toxicodynamics of oxaliplatin in rats: application of a toxicity factor to explain differences in the nephrotoxicity and myelosuppression induced by oxaliplatin and the other platinum antitumor derivatives.

Purpose: We previously reported that the product of the area under the plasma concentration-time curve (AUC(p)) and a toxicity factor, which in turn was defined as the product of the apparent ratio of tissue to plasma concentration (Kp(app)) and the apparent hydrolysis rate constant (k(hydrolysis)), was a determinant of the different degrees of toxicities induced by platinum drugs, cisplatin, carboplatin and nedaplatin. We tested this model with oxaliplatin.

Methods: Oxaliplatin was administered to rats by intravenous bolus or infusion, and the linearity of pharmacokinetics, total clearance and the Kp(app) at steady state were determined.

Affinity improvement of the high-affinity immunoglobulin E receptor by phage display.

The immunoglobulin E (IgE)-binding site of its high-affinity receptor is localized in the second immunoglobulin-like domain (D2) of the alpha-subunit (Fc epsilon RI alpha). In this study, the randomized pentapeptides were introduced between Glu(132) and Ile(138) of Fc epsilon RI alpha D2 and displayed on a filamentous phage. After eight rounds of panning, a phage clone having a mutation of Asp(135)Tyr(136)Met(137) in Fc epsilon RI alpha D2 was obtained.