Microdosing as a Potential Tool to Enhance Clinical Development of Novel Antibiotics: A Tissue and Plasma PK Feasibility Study with Ciprofloxacin
Clinical Pharmacokinetics January 7, 2022 Z. Oesterreicher, Sabine Eberl, B. Wulkersdorfer et al.
A single intravenous microdose of radiolabeled ciprofloxacin (1.1 µg) can accurately predict the drug's pharmacokinetics in plasma and subcutaneous tissue but not in epithelial lining fluid. Healthy volunteers received the microdose either with or without a prior therapeutic dose (400 mg). The dose-adjusted area under the concentration–time curve in plasma and subcutaneous tissue was similar between the microdose and therapeutic dose, with ratios within 0.8 to 1.1. Penetration into subcutaneous tissue was comparable across conditions, with tissue-to-plasma ratios of 0.44, 0.44, and 0.38. However, microdose penetration into epithelial lining fluid was highly variable and did not predict therapeutic-dose penetration. Microdosing with microdialysis may aid antimicrobial drug development but requires further study for pulmonary assessments.