ABSORPTION ENHANCEMENT OF A HYDROPHILIC MODEL-COMPOUND BY VERAPAMIL AFTER RECTAL ADMINISTRATION TO RATS

The use of verapamil as an absorption enhancer for the paracellular ro ute in-vivo was studied using FITC-labelled dextran (molecular weight 4000) (FD-4) as a hydrophilic model compound for transport enhancement . The kinetics of FD-4 after intravenous doses of 1 or 10mg could be d escribed by a two-compartment model with a systemic clearance of appro ximately 2mLmin(-1) and a terminal plasma half-life of approximately 3 6min. Rectal administration to rats, performed as a rectal infusion of 10mg FD-4 together with 7mM verapamil, resulted in a 10-fold increase in the percentage of the dose absorbed over a 5-h period compared wit h the control and a 6-fold increase compared with a bolus administrati on, although the total amount absorbed remained relatively low (approx . 3% maximum). Large inter-animal variation in effect values were note d. The data indicate that although verapamil is able to enhance the ab sorption of hydrophilic compounds in-vivo, practical application of ve rapamil for this purpose does not seem feasible.