IN-VITRO BINDING OF PROPIVERINE HYDROCHLORIDE AND SOME OF ITS METABOLITES TO SERUM-ALBUMIN IN MAN

The distribution and pharmacological action of propiverine, a bladder spasmolytic agent, are affected by the extent of plasma-protein bindin g. Because attempts to assess the albumin-binding of propiverine have produced conflicting results, the binding parameters of the drug and s ome of its metabolites to serum albumin in man have been re-evaluated. In man propiverine is bound to serum albumin at a single site with hi gh affinity (K-A1 = 1.45 x 10(4) L mol(-1)) and at least two sites wit h low affinity (K-A2 = 2.5 x 10(2) L mol(-1)). The metabolites of prop iverine, namely M2 (dealkylated propiverine), M5 (the N-oxide of propi verine) and M6 (the N-oxide of M2), are less firmly bound to serum alb umin; this is considered to be non-specific binding. Binding experimen ts with human serum revealed that there are additional binding protein s. At therapeutic plasma levels the extent of binding was calculated t o be 90, 15, 60, and 20% for propiverine and the metabolites M2, M5, a nd M6, respectively. The strong binding of propiverine to serum protei ns controls its availability to the liver. Because the metabolites are not tightly bound to serum proteins, after metabolism of propiverine its metabolites are easily eliminated.