Abstract
A general treatment of enterohepatic recirculation of drugs has been developed based on the fraction of drug in systemic circulation that is excreted in the bile and the fraction of drug reabsorbed from the gut that reaches systemic circulation in each enterohepatic cycle. The deduced equations make it possible to establish mathematical relationships between the areas under the blood level curves (AUC) of a drug when administered to normal and bile duct-cannulated animals and to predict the effect of enterohepatic recycling on bio-availability and clearance. The results were compared with those obtained by other authors using different approaches to enterohepatic recirculation, and some discrepancies were found in the equations describing the effect of enterohepatic recycling on AUC and bioavailability of drugs. The cause of such discrepancies and the problems associated with the prediction of hepatic extraction ratio from in vitro studies are discussed.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
K. S. Pang and J. R. Gillette. A theoretical examination of the effects of gut wall metabolism, hepatic elimination, and enterohepatic recycling on estimates of bioavailability and of hepatic blood flow. J. Pharmacokin. Biopharm. 6:355–367 (1978).
H. G. Chen and J. F. Gross. Pharmacokinetics of drugs subject to enterohepatic circulation. J. Pharm. Sci. 68:792–794 (1979).
P. Veng-Pedersen and R. Miller. Pharmacokinetics and bioavailability of cimetidine in humans. J. Pharm. Sci. 69:394–398 (1980).
W. A. Colburn. Pharmacokinetic and biopharmaceutic parameters during enterohepatic circulation of drugs. J. Pharm. Sci. 71:131–133 (1982).
J. L. Steimer, Y. Plusquellec, A. Guillaume, and J. F. Boisvieux. A time-lag model for pharmacokinetics of drugs subject to enterohepatic circulation. J. Pharm. Sci. 71:297–302 (1982).
W. A. Colburn. Pharmacokinetic analysis of concentration-time data obtained following administration of drugs that are recycled in the bile. J. Pharm. Sci. 73:313–317 (1984).
T. A. Shepard, D. J. Gannaway, and G. F. Lockwood. Accumulation and time to steady state for drugs subject to enterohepatic cycling: A simulation study. J. Pharm.Sci. 74:1331–1333 (1985).
T. A. Shepard and R. H. Reuning. An equation for the systemic availability of drugs undergoing simultaneous enterohepatic cycling, first-pass metabolism, and intestinal elimination. Pharm. Res. 4:195–199 (1987).
F. L. S. Tse, F. Ballard, and J. Skinn. Estimating the fraction reabsorbed in drugs undergoing enterohepatic circulation. J. Pharmacokin. Biopharm. 10:455–461 (1982).
K. Yamaoka, M. Kanba, Y. Toyoda, Y. Yano, and T. Nakagawa. Analysis of enterohepatic circulation of cefixime in rat by fast inverse Laplace transform (FILT). J. Pharmacokin. Biopharm. 18:545–559 (1990).
J. B. Dressman, G. L. Amidon, and D. Fleisher. Absorption potential: Estimating the fraction absorbed for orally administered compounds. J. Pharm. Sci. 74:588–589 (1985).
A. Rane, G. R. Wilkinson, and D. G. Shand. Prediction of hepatic extraction ratio from in vitro measurement of intrinsic clearance. J. Pharmacol. Exp. Ther. 200:420–424 (1977).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Peris-Ribera, JE., Torres-Molina, F., Garcia-Carbonell, M.C. et al. General Treatment of the Enterohepatic Recirculation of Drugs and Its Influence on the Area Under the Plasma Level Curves, Bioavailability, and Clearance. Pharm Res 9, 1306–1313 (1992). https://doi.org/10.1023/A:1015861502354
Issue Date:
DOI: https://doi.org/10.1023/A:1015861502354