Design, Synthesis, and Pharmacokinetic Evaluation of Phosphate and Amino Acid Ester Prodrugs for Improving the Oral Bioavailability of the HIV-1 Protease Inhibitor Atazanavir.

Phosphate and amino acid prodrugs of the HIV-1 protease inhibitor (PI) atazanavir (1) were prepared and evaluated to address solubility and absorption limitations. While the phosphate prodrug failed to release 1 in rats, the introduction of a methylene spacer facilitated prodrug activation, but parent exposure was lower than that following direct administration of 1. Val amino acid and Val-Val dipeptides imparted low plasma exposure of the parent, although the exposure of the prodrugs was high, reflecting good absorption.

Coupling of an Acyl Migration Prodrug Strategy with Bio-activation To Improve Oral Delivery of the HIV-1 Protease Inhibitor Atazanavir.

HIV-1 protease inhibitors (PIs), which include atazanavir (ATV, 1), remain important medicines to treat HIV-1 infection. However, they are characterized by poor oral bioavailability and a need for boosting with a pharmacokinetic enhancer, which results in additional drug-drug interactions that are sometimes difficult to manage. We investigated a chemo-activated, acyl migration-based prodrug design approach to improve the pharmacokinetic profile of 1 but failed to obtain improved oral bioavailability over dosing the parent drug in rats.

Comparison of Levosimendan versus Dobutamine in Patients with Moderate to Severe Left Ventricular Dysfunction Undergoing Off-pump Coronary Artery Bypass Grafting: A Randomized Prospective Study.

Context: Recent upsurge in referral of patients with compromised left ventricular (LV) function for cardiac surgery has led to an increasing use inotropes to achieve improvement of tissue perfusion in the perioperative period.

Aims And Objectives: To compare the hemodynamic effects and immediate postoperative outcomes with levosimendan and dobutamine in patients with moderate to severe LV dysfunction undergoing off-pump coronary artery bypass grafting (OPCAB).

Settings And Design: University teaching hospital, randomized control study.

Character and spatial distribution of OH/H2O on the surface of the Moon seen by M3 on Chandrayaan-1.

The search for water on the surface of the anhydrous Moon had remained an unfulfilled quest for 40 years. However, the Moon Mineralogy Mapper (M3) on Chandrayaan-1 has recently detected absorption features near 2.8 to 3.