Validation of a new intraarterial microdialysis shunt probe for the estimation of pharmacokinetic parameters.
The aim of our study was to compare pharmacokinetic parameters of a highly bound protein drug, irbesartan, obtained from microdialysis data (MD) of arterial blood and conventional blood samples (BS). A new vascular shunt microdialysis probe was inserted into the carotid artery and one femoral vein was cannulated for i.v. administration of irbesartan. Microdialysis samples were collected every 15 min. Blood samples were taken every 15 min. Levels of drug were measured by HPLC. Pharmacokinetic parameters were estimated using TOPFIT program. Corrected MD were compared with BS taken at same time to determine protein binding. The irbesartan protein binding did not change during the experiment. The estimated Ke from MD and BS were similar (MD: 1.8+/-0.3 h(-1), n=5; BS: 1.7+/-0.2 h(-1), n=5). After protein binding correction for the MD, the estimated values of volume of distribution (Vd) (MD: 1.2+/-0.4 l, n=5; BS: 1.1+/-0.4 l, n=5), clearance (Cl) (MD: 32.3+/-7.3 ml min(-1), n=5; BS: 30.7+/-8.2 ml min(-1), n=5) and AUC (MD: 7.7+/-3.2 microg x ml(-1) h, n=5; BS: 8.8+/-3.4 microg x ml(-1) h, n=5) were similar between MD and BS. In conclusion, these results show that our new probe inserted in the carotid artery provides accurate MD to estimate pharmacokinetic parameters of a highly bound protein drug like irbesartan. On the other hand, MD were also useful to the in vivo study of drug protein binding and saturation in protein binding.
Höcht
Christian
C
Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, (C1113AAD), Buenos Aires, Argentina. chocht@ffyb.uba.ar
Opezzo
JavierA W
JW
Taira
CarlosA
C
D000818:Animals; D001713:Biphenyl Compounds / Q000097:blood* / Q000493:pharmacokinetics*; D002339:Carotid Arteries / Q000378:metabolism* / Q000601:surgery; D000077405:Irbesartan; D008297:Male; D017551:Microdialysis / Q000295:instrumentation* / Q000379:methods*; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000097:blood* / Q000493:pharmacokinetics*; D014159:Transducers
D001713:Biphenyl Compounds; D013777:Tetrazoles; D000077405:Irbesartan