Assessment of in vitro and in vivo recovery of sinomenine using microdialysis

Abstract

For microdialysis studies in the skin, laboratory-made linear probes are often used. The application of the microdialysis technique to the investigation of pharmacokinetics and pharmacodynamics of drugs requires careful assessment of the linear probes' performance to ensure validity of the data obtained using this technique. The aim of this study was to establish and validate the microdialysis technique for investigation of the pharmacokinetics and pharmacodynamics of sinomenine. Using different lengths of the dialysis membrance and different perfusion flow rates, a flow rate of 2 microL/min with 20-min sampling intervals was selected for the subsequent studies, based on the analysis of sinomenine from the microdialysis probe. In vitro recovery of sinomenine from the microdialysis probe was independent of concentration, stable over an 8-h period. Comparable in vitro recoveries were obtained by different established approaches including recovery estimation by gain, loss and the zero-net flux (ZNF) method. Recovery by loss was used to study the in vivo recovery of sinomenine from rat subcutaneous tissue. The performance of the microdialysis system was stable over an 8-h study, resulting in a mean in vitro recovery of 51.91+/-1.29%. Recovery obtained using the ZNF plot was 52.43%. In vivo recovery of sinomenine was 34.46+/-0.76% and was stable over the 7-h study period. The in vitro and in vivo performance of the microdialysis technique was established for the study of sinomenine. It would prove to be a useful and reliable tool to study the pharmacokinetics and pharmacodynamics of sinomenine. The data obtained in our study highlight the importance of a systematic examination of microdialysis linear probe validation.