title: Absorption enhancement of a hydrophilic model compound by verapamil after rectal administration to rats.
abstract: 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.
authors.affiliation: Leiden/Amsterdam Center for Drug Research, Leiden University, The Netherlands.
authors.forename: A B
authors.initials: AB
authors.lastname: Noach
authors.forename: M C
authors.initials: MC
authors.lastname: Blom-Roosemalen
authors.forename: A G
authors.initials: AG
authors.lastname: De Boer
authors.forename: D D
authors.initials: DD
authors.lastname: Breimer
mesh_terms: D000285:Administration, Rectal; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003911:Dextrans / Q000494:pharmacology; D005079:Excipients; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000494:pharmacology; D006207:Half-Life; D007275:Injections, Intravenous; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014700:Verapamil / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D003911:Dextrans; D005079:Excipients; C015219:fluorescein isothiocyanate dextran; D014700:Verapamil; D016650:Fluorescein-5-isothiocyanate