Validation of microdialysis sampling for oral availability studies by means of a new ganciclovir prodrug

• Published in: Pharmacology & toxicology Vol. 90; no. 6; p. 297
• Main Authors: Lindén, Karin, Zhou, Xiao-Xiong, Ståble, Lans
• Format: Journal Article
• Language: English
• Published: Denmark 01.06.2002
• Subjects: Administration, Oral; Animals; Antiviral Agents - pharmacokinetics; Area Under Curve; Biological Availability; Ganciclovir - administration & dosage; Ganciclovir - blood; Ganciclovir - urine; Guanine - analogs & derivatives; Guanine - pharmacokinetics; Male; Microdialysis; Prodrugs - pharmacokinetics; Rats; Rats, Sprague-Dawley; Time Factors
• ISSN: 0901-9928
• DOI: 10.1034/j.1600-0773.2002.900602.x

Microdialysis sampling was validated for oral availability studies using ganciclovir (9-(1, 3-dihydroxy-2-propoxymethyl) guanine) and a ganciclovir prodrug (9-(1-L-valyloxy-3-octadecanoyloxy-prop-2-oxymethyl) guanine). Three different techniques were used in the study; microdialysis, blood and urinesampling. The oral uptake (11+/-2%) and the urinary recovery (106+/-5%) were determined. Animals given ganciclovir subcutaneously were subject either to microdialysis and blood sampling or to microdialysis alone. There was no significant difference between microdialysis and blood sampling in terms of blood concentration data, CL, Vd, half-life or AUC by means of Student's t-test. The oral bioavailability of the prodrug was 40+/-7% estimated from microdialysis sampling data and 48+/-4% estimated from urine sampling data. It is concluded that microdialysis is a valid method to use in pharmacokinetic studies of oral availability as well as for basic pharmacokinetic parameter estimation.