A Recirculatory Model for Local Absorption and Disposition of Ciprofloxacin by Measuring Portal and Systemic Blood Concentration Difference

A recirculatory model for the portal–systemic blood concentration difference (P–S difference) was developed to separately evaluate the rate and extent of absorption from the gastrointestinal tract into the portal system and disposition of a drug in the body. To apply this model to pharmacokinetic analysis, ciprofloxacin was selected as a model drug possessing a moderate intestinal absorption, and renal and hepatic elimination. The portal and systemic blood samples were simultaneously taken from rats at appropriate time points after intravenous and oral administration of ciprofloxacin at a dose of 5 mg/kg. After intravenous administration, little or no difference in the concentrations between the portal and systemic blood was observed, whereas after oral administration the concentrations of ciprofloxacin in the portal blood were consistently higher than those in the systemic blood over the time studied. This difference observed after oral administration is attributed to the absorption of ciprofloxacin from the gastrointestinal tract into the portal system. On the basis of the moment analysis deduced from the recirculatory model, the portal blood flow rate (Qp), the local absorption ratio from the gastrointestinal tract into the portal system (Fa), the hepatic recovery ratio (Fh), and bioavailability (BA) were then estimated. The obtained Qp of 2.81 L/h/kg, Fa of 32.6, Fh of 68.1, and BA of 22.2% were found to be in good agreement with the reported values. Furthermore, the mean local absorption time from the gastrointestinal tract into the portal system (t―a) calculated by a nonlinear least‐squares program [MULTI (FILT)] was almost identical with that by the global moments. These results suggest that the model proposed in this study would be useful for evaluating both in vivo absorption and disposition of drugs. © 2002 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:196–205, 2002