Two hours after a single intravenous dose of ketamine (0.8 mg/kg over 50 minutes), healthy adults showed a reduction in the ratio of GABA to total creatine in the hippocampus, as measured by magnetic resonance spectroscopic imaging. No significant changes were observed in the glutamate-plus-glutamine ratio or the GABA-to-glutamate-plus-glutamine ratio across seven brain regions. Plasma levels of ketamine and its metabolites norketamine and dehydronorketamine were not significantly associated with changes in any neurotransmitter ratio. The findings suggest that ketamine may alter GABA turnover in the hippocampus, a region relevant to its emerging antidepressant effects.
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.