higher AUC after bolus compared to infusion?

Dear all, I have trouble modeling some rat PK data obtained after intravenous dosing. I have dense data for two different doses, given either as bolus, half-hour or 3-hour infusion. We know that the compound has a large binding affinity to intracellular structures and therefore has a high volume of distribution (~100L/kg in rats). However, what we observed in the mentioned study is that the AUC after bolus dosing is ~3 times higher than after infusions (no difference between 0.5 and 3 h), and this was observed for both dose groups (effect a bit less pronounced for high dose, but still there). Noncompartmental analysis indicates that this is due to lower clearance and not a change in Vss. At the moment I have no idea what kind of model would capture an observation like this. Has anybody ever observed something like this, and even better, have some ideas on model coding? Any ideas would be welcome! Best regards Nele _________________________________________ Bayer Schering Pharma AG Development Pharmacokinetics Berlin, S109, 03, 306A Phone: +49 30 468-15146 Fax: +49 30 468-11527 E-mail: [EMAIL PROTECTED] Web: http://www.bayerscheringpharma.de Vorstand: Andreas Fibig, Vorsitzender | Werner Baumann, Andreas Busch, Ulrich Köstlin, Kemal Malik, Bernd Metzner, Gunnar Riemann Vorsitzender des Aufsichtsrats: Werner Wenning Sitz der Gesellschaft: Berlin | Eintragung: Amtsgericht Charlottenburg HRB 283 B