INTRAVESICAL INSTILLATION OF TERODILINE - AN IN-VIVO STUDY OF DRUG ABSORPTION IN RABBIT AND MAN

The absorption of intravesically administered terodiline was investiga ted in 8 healthy volunteers (10(-4)) and in 33 rabbits (10(-4) M., 4 x 10(-4) M. and 1.6 x 10(-3) M.). In the humans, the amount of drug ret ained and the serum concentration were registered. In the rabbits, the influence of drug concentration, pH (5 and 9.2) and volume (5 and 20 ml.) were evaluated. Liquid scintigraphy of the bladder wall and of se rum and tissue samples from striated muscle, kidney and liver was perf ormed. Further, autoradiography of the bladder wall and calculation of drug retention were done. In the humans, 20 +/-5% of the administered terodiline dose was retained in the body. Clinically significant seru m concentrations were not detected. In the rabbits, 21 +/-4% of the dr ug was retained with the pH=5 terodiline solution as compared with 64 +/-3% with the pH = 9.2 solution. With increasing terodiline concentra tions, drug retention increased. as did the tissue and serum activitie s. At a given concentration, the total amount of drug retained increas ed with a larger volume. The drug gradient between the bladder muscle layer and serum was of a magnitude of about 100, independent of the dr ug concentration within the muscle layer. It is concluded that the pH and concentration of the solution are factors of major importance for the amount of terodiline absorbed from the bladder. Compared with the one obtainable by systemic drug administration, the large gradient bet ween the bladder muscle and the serum is conspicuous, and may be of cl inical interest.