PHARMACOKINETIC MONITORING IN SUBCUTANEOUS TISSUE USING INVIVO CAPILLARY ULTRAFILTRATION PROBES

被引:27
作者
LINHARES, MC [1 ]
KISSINGER, PT [1 ]
机构
[1] PURDUE UNIV,DEPT CHEM,W LAFAYETTE,IN 47907
关键词
CAPILLARY ULTRAFILTRATION; INVIVO SAMPLING; PHARMACOKINETICS; ACETAMINOPHEN; THEOPHYLLINE; SUBCUTANEOUS TISSUE;
D O I
10.1023/A:1018914522749
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Capillary ultrafiltration probes were utilized for in vivo sampling of therapeutic drugs in awake rats. Capillary ultrafiltration probes implanted into subcutaneous tissue were able to follow the disposition of acetaminophen and theophylline. Ultrafiltration probes provided samples at a rate of 2-3 muL/min. Ultrafiltrates were analyzed by liquid chromatography with either UV or electrochemical detection. Simultaneous ultrafiltration and microdialysis probes and multiple ultrafiltration probes were used in individual animals to validate the technique. The pharmacokinetics of two well-established drugs, acetaminophen and theophylline, were monitored in awake, freely moving rats to demonstrate the viability of the technique. The half-life for acetaminophen was determined to be 20.9 +/- 1.0 min (n = 6) for a 2 mg/kg dosing. The half-life of elimination for theophylline was determined to be 3.0 +/- 0.1 hr (n = 4) for a 4 mg/kg dose. The capillary ultrafiltration probes exhibited a constant flow rate of 2.4 +/- 0.1 muL/min and removed 50 nL/min/mm of fluid from the extracellular space. Capillary ultrafiltration sampling is shown to be an excellent tool for in vivo monitoring of drug disposition and a suitable method for determining pharmacokinetic parameters in awake animals.
引用
收藏
页码:598 / 602
页数:5
相关论文
共 15 条
[1]  
BUNGEY PM, 1991, J NEUROCHEM, V57, P103
[2]  
Creasey W.A., 1979, DRUG DISPOSITION HUM
[3]   CAPILLARY ULTRAFILTRATION - INVIVO SAMPLING PROBES FOR SMALL MOLECULES [J].
LINHARES, MC ;
KISSINGER, PT .
ANALYTICAL CHEMISTRY, 1992, 64 (22) :2831-2835
[4]  
LINHARES MC, 1992, TRAC-TREND ANAL CHEM, V11, P171
[5]   INVIVO SAMPLING USING LOOP MICRODIALYSIS PROBES COUPLED TO A LIQUID CHROMATOGRAPH [J].
LINHARES, MC ;
KISSINGER, PT .
JOURNAL OF CHROMATOGRAPHY-BIOMEDICAL APPLICATIONS, 1992, 578 (02) :157-163
[6]   SAMPLING LIVING SYSTEMS USING MICRODIALYSIS PROBES [J].
LUNTE, CE ;
SCOTT, DO ;
KISSINGER, PT .
ANALYTICAL CHEMISTRY, 1991, 63 (15) :A773-+
[7]   INVIVO CALIBRATION OF MICRODIALYSIS PROBES FOR EXOGENOUS COMPOUNDS [J].
MENACHERRY, S ;
HUBERT, W ;
JUSTICE, JB .
ANALYTICAL CHEMISTRY, 1992, 64 (06) :577-583
[8]  
OGIVE R, 1978, CLIN PHARMACOKINET, V3, P267
[9]  
Ritschel W. A., 1976, HDB BASIC PHARMACOKI
[10]   INVIVO MICRODIALYSIS SAMPLING FOR PHARMACOKINETIC INVESTIGATIONS [J].
SCOTT, DO ;
SORENSON, LR ;
STEELE, KL ;
PUCKETT, DL ;
LUNTE, CE .
PHARMACEUTICAL RESEARCH, 1991, 8 (03) :389-392