Population Pharmacokinetics and Safety of Solithromycin Following Intravenous and Oral Administration in Infants, Children, and Adolescents [PublishAheadOfPrint]

Solithromycin is a novel fluoroketolide antibiotic, which was under investigation for the treatment of community-acquired bacterial pneumonia (CABP). A phase 1 study was performed to characterize the pharmacokinetics (PK) and safety of solithromycin in children. Eighty-four subjects (median age 6 years [range 4 days - 17 years]) were administered intravenous (IV) or oral (capsules or suspension) solithromycin (IV 6-8 mg/kg; capsules/suspension 14-16 mg/kg on Day 1 and 7-15 mg/kg on Days 2-5). PK samples were collected after first and multi-dose administration. Data from 83 subjects (662 samples) were combined with previously collected adolescent PK data (N=13, median [range] age 16 years (12-17)) following capsule administration to perform a population PK analysis. A 2-compartment PK model characterized the data well, and post-menstrual age was the only significant covariate after accounting for body size differences. Dosing simulations suggested that 8 mg/kg IV daily and oral dosing of 20 mg/kg on Day 1 (800 mg adult maximum) followed by 10 mg/kg on Days 2-5 (400 mg adult maximum) would achieve pediatric solithromycin exposure consistent with exposures observed in adults. Seventy-six treatment-emergent adverse events (TEAEs) were reported in 40 subjects. Diarrhea (6 subjects) and infusion site pain or phlebitis (3 subjects) were the most frequently reported adverse events related to treatment. Two subjects experienced TEAEs of increased hepatic enzymes that were deemed not to be related to study treatment.

https://ift.tt/2Jvxwhm