Assaying protein unbound drugs using microdialysis techniques.
Compared with traditional sampling methods, microdialysis is a technique for protein unbound drug sampling without withdrawal of biological fluids and involving minimal disturbance of physiological function. Conventional total drug sample consists of unbound drugs and protein bound drugs, which are loosely bound to plasma proteins such as albumin and alpha-1 acid glycoprotein, forming an equilibrium ratio between bound and unbound drugs. However, only the unbound fraction of drug is available for absorption, distribution, metabolism and elimination, and delivery to the target sites for pharmacodynamic actions. Although several techniques have been used to determine protein unbound drugs from biological fluids, including ultrafiltration, equilibrium dialysis and microdialysis, only microdialysis allows simultaneous sampling of protein unbound chemicals from plasma, tissues and body fluids such as the bile juice and cerebral spinal fluid for pharmacokinetic and pharmacodynamic studies. This review article describes the technique of microdialysis and its application in pharmacokinetic studies. Furthermore, the advantages and limitations of microdialysis are discussed, including the detailed surgical techniques in animal experiments from rat blood, brain, liver, bile duct and in vitro cell culture for unbound drug analysis.
Tsai
Tung-Hu
TH
Laboratory of Pharmacokinetics, National Research Institute of Chinese Medicine, Taipei 112, Taiwan. thtsai@nricm.edu.tw
D017551:Microdialysis / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000737:chemistry; D011506:Proteins / Q000737:chemistry*; D014018:Tissue Distribution
D004364:Pharmaceutical Preparations; D011506:Proteins