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 route 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 10 mg could be described by a two-compartment model with a systemic clearance of approximately 2 mL min-1 and a terminal plasma half-life of approximately 36 min. Rectal administration to rats, performed as a rectal infusion of 10 mg FD-4 together with 7 mM verapamil, resulted in a 10-fold increase in the percentage of the dose absorbed over a 5-h period compared with the control and a 6-fold increase compared with a bolus administration, although the total amount absorbed remained relatively low (approx. 3% maximum). Large inter-animal variation in effect values were noted. The data indicate that although verapamil is able to enhance the absorption of hydrophilic compounds in-vivo, practical application of verapamil for this purpose doses not seem feasible.