First-Time-in-Human Study and Prediction of Early Bactericidal Activity for GSK3036656, a Potent Leucyl-tRNA Synthetase Inhibitor for Tuberculosis Treatment.

This first-time-in-human (FTIH) study evaluated the safety, tolerability, pharmacokinetics, and food effect of single and repeat oral doses of GSK3036656, a leucyl-tRNA synthetase inhibitor. In part A, GSK3036656 single doses of 5 mg (fed and fasted), 15 mg, and 25 mg and placebo were administered. In part B, repeat doses of 5 and 15 mg and placebo were administered for 14 days once daily.

Pharmacokinetics and absolute bioavailability of mepolizumab following administration at subcutaneous and intramuscular sites.

This study characterized the pharmacokinetics (PK) of mepolizumab, after a single intravenous (IV), subcutaneous (SC), or intramuscular (IM) dose in healthy adults and determined the absolute bioavailability of SC and IM mepolizumab delivered at different anatomical regions. Sixty healthy subjects were randomly assigned to receive a single dose of either mepolizumab 250 mg by IV, SC injection (upper arm, abdomen, or thigh); or IM injection (thigh). Following IV administration, the mean maximum observed plasma mepolizumab concentration (Cmax ) and the mean area under the concentration versus time curves from time zero to infinity (AUC(0-∞) ) were 109 ± 17 µg/mL and 1,557 ± 250 µg d/mL, respectively.

Radical curative efficacy of tafenoquine combination regimens in Plasmodium cynomolgi-infected Rhesus monkeys (Macaca mulatta).

Background: Tafenoquine is an 8-aminoquinoline being developed for radical cure (blood and liver stage elimination) of Plasmodium vivax. During monotherapy treatment, the compound exhibits slow parasite and fever clearance times, and toxicity in glucose-6-phosphate dehydrogenase (G6PD) deficiency is a concern. Combination with other antimalarials may mitigate these concerns.