Peritoneal microdialysis in freely moving rodents: an alternative to blood sampling for pharmacokinetic studies in the rat and the mouse.
By performing microdialysis in the peritoneal cavity, we studied the pharmacokinetics of Tramadol in awake, freely moving small laboratory animals. The systemic exposure to Tramadol was determined using both microdialysis sampling and collection of whole blood following a single intravenous injection (10 mg/kg) or a single oral dose (100 mg/kg) of Tramadol HCl. The sampling frequency of the dialysate was 10 min (mouse study) or 20 min (rat study). In rats and in mice, intraperitoneal microdialysis sampling gets reliable pharmacokinetic results without taking blood. The concentration-time curves obtained from peritoneal microdialysis were parallel to the concentration-time curves obtained from classical blood sampling. Accordingly, dose independent pharmacokinetic parameters were similar. A scaling factor, however, has to be introduced (e.g. peritoneal versus plasma AUC ratio) in order to obtain comparable pharmacokinetic results also with dose-dependent parameters. As there was no blood loss during the experiment, peritoneal microdialysis allowed the investigation of complete concentration-time curve profiles. Thus, the number of animals could be kept to a minimum. In conclusion, in vivo peritoneal microdialysis is a unique tool to obtain a complete set of free drug concentrations to determine reliable pharmacokinetic parameters from awake, freely moving rodents. Therefore, we suppose that the technique will have relevance for pharmacokinetic studies in future.
Beier
Horst
H
Department of Pharmacokinetics, Grünenthal GmbH, Zieglerstr. 6, 52078 Aachen, Germany. horst.beier@grunenthal.com
Kaiser
Katharina
K
Langhans
Manfred
M
Malmendier
Klaus
K
Sluijsmans
Ivo
I
Weiher
Jürgen
J
D000284:Administration, Oral; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D001800:Blood Specimen Collection; D004305:Dose-Response Relationship, Drug; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D017551:Microdialysis / Q000379:methods; D010537:Peritoneum / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014147:Tramadol / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*
D000701:Analgesics, Opioid; D014147:Tramadol