TY - JOUR
T1 - The design and validation of a novel intravenous microdialysis probe
T2 - Application to fluconazole pharmacokinetics in the freely-moving rat model
AU - Yang, Hua
AU - Wang, Qin
AU - Elmquist, William F.
PY - 1997
Y1 - 1997
N2 - Purpose. The purpose of this study was to design and validate a concentric, flexible intravenous microdialysis probe to determine drug concentrations in blood from the inferior vena cava of a freely-moving animal model. Methods. An intravenous microdialysis probe was constructed using fused-silica tubing and an acrylonitrile/sodium methallyl sulfonate copolymer hollow fiber. The probe was tested in vitro for the recovery of fluconazole and UK-54,373, a fluconazole analog used for probe calibration by retrodialysis. Subsequent in vivo validation was done in rats n = 7) that had a microdialysis probe inserted into the inferior vena cava via the femoral vein, and the femoral artery was cannulated for simultaneous blood sampling. Comparisons of fluconazole pharmacokinetic parameters resulting from the two sampling methods were performed at 2 and 10 days after probe implantation. Results. There were no statistical differences between the microdialysis sampling and conventional blood sampling methods for the T( 1/4 ), Cl, Vdss, and dose-normalized AUC by paired t-test (p > 0.05) for repeated dosing at day 2 and day 10 after probe placement. The probe recovery, as determined by retrodialysis, significantly decreased over the ten day period. This finding indicates the necessity for frequent recovery determinations during a long-term blood microdialysis experiment. Conclusions. These results show that microdialysis sampling in the inferior vena cava using this unique and robust probe design provides an accurate method of determining blood pharmacokinetics in the freely-moving rat for extended experimental periods. The probe design allows for a simple surgical placement into the inferior vena cava which results in a more stable animal preparation for long-term sampling and repeated-measures experimental designs.
AB - Purpose. The purpose of this study was to design and validate a concentric, flexible intravenous microdialysis probe to determine drug concentrations in blood from the inferior vena cava of a freely-moving animal model. Methods. An intravenous microdialysis probe was constructed using fused-silica tubing and an acrylonitrile/sodium methallyl sulfonate copolymer hollow fiber. The probe was tested in vitro for the recovery of fluconazole and UK-54,373, a fluconazole analog used for probe calibration by retrodialysis. Subsequent in vivo validation was done in rats n = 7) that had a microdialysis probe inserted into the inferior vena cava via the femoral vein, and the femoral artery was cannulated for simultaneous blood sampling. Comparisons of fluconazole pharmacokinetic parameters resulting from the two sampling methods were performed at 2 and 10 days after probe implantation. Results. There were no statistical differences between the microdialysis sampling and conventional blood sampling methods for the T( 1/4 ), Cl, Vdss, and dose-normalized AUC by paired t-test (p > 0.05) for repeated dosing at day 2 and day 10 after probe placement. The probe recovery, as determined by retrodialysis, significantly decreased over the ten day period. This finding indicates the necessity for frequent recovery determinations during a long-term blood microdialysis experiment. Conclusions. These results show that microdialysis sampling in the inferior vena cava using this unique and robust probe design provides an accurate method of determining blood pharmacokinetics in the freely-moving rat for extended experimental periods. The probe design allows for a simple surgical placement into the inferior vena cava which results in a more stable animal preparation for long-term sampling and repeated-measures experimental designs.
KW - Blood sampling
KW - Fluconazole
KW - Intravenous microdialysis
KW - Pharmacokinetics
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U2 - 10.1023/A:1012137209042
DO - 10.1023/A:1012137209042
M3 - Article
C2 - 9358561
AN - SCOPUS:0030779676
SN - 0724-8741
VL - 14
SP - 1455
EP - 1460
JO - Pharmaceutical research
JF - Pharmaceutical research
IS - 10
ER -