Intravesical Instillation of Terodiline—An in Vivo Study of Drug Absorption in Rabbit and Man

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Abstract
The absorption of intravesically administered terodiline was investigated 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 retained 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 serum and tissue samples from striated muscle, kidney and liver was performed. 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 serum concentrations were not detected. In the rabbits, 21 +/- 4% of the drug was retained with the pH = 5 terodiline solution as compared with 64 +/- 3% with the pH = 9.2 solution. With increasing terodiline concentrations, drug retention increased, as did the tissue and serum activities. At a given concentration, the total amount of drug retained increased with a larger volume. The drug gradient between the bladder muscle layer and serum was of a magnitude of about 100, independent of the drug 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 between the bladder muscle and the serum is conspicuous, and may be of clinical interest.