Pharmacokinetic applications of cutaneous microdialysis: Continuous + intermittent vs continuous-only sampling

Abstract

IntroductionMicrodialysis is a technique that allows interstitial-fluid sampling with minimal tissue-damage. In a microdialysis study, samples are collected serially (continuous microdialysis, CMD) and participant's movements are reduced for the entire study. Intermittent Cutaneous Microdialysis (IMD) is a modified version of CMD, which allows for unrestrained periods in between samples. However, in separate experiments, pharmacokinetic parameters estimated with IMD showed higher variability than with CMD. The purpose of this study is to simultaneously assess and compare the skin pharmacokinetic profiles obtained with a combination of CMD and IMD with those obtained with traditional CMD sampling only, in the same experiment. MethodsTwo linear microdialysis (MD) probes were inserted into the shaved dorsal skin of three rabbits. Following the oral administration of three different doses (20, 40 and 80mg/kg) of ciprofloxacin (CPLX), for the first 2h, samples were collected from both probes according to traditional CMD in order to assess intrinsic differences between the two sites. After 2h, one of the probes was switched to IMD schedule. Skin-exposure parameters were estimated with non-compartmental analysis. ResultsTwo of the nine experiments showed a difference larger than 30% between the concentrations measured from the two probes when both were on the CMD schedule. Otherwise, the skin concentration profiles were almost superimposable. Pharmacokinetic parameters were not statistically different. ConclusionThe results of this study show that skin pharmacokinetic parameters measured via a combination of CMD and IMD were not statistically different from those estimated via traditional CMD sampling alone.