Bioavailability and diuretic effect of @entity1483 during long-term treatment of XXXX .

@entity1 @entity1372 @entity1483 @entity1576
The bioavailability and diuretic effect of @entity1483 40 mg administered orally for at least 6 months have been compared in @entity1 with @entity1576 and in healthy controls. The mean urinary recovery of unchanged drug was 11.5 mg and 9.41 mg in 24 h after pre- and postprandial administration to 10 @entity1 , whereas the recovery was 14.4 mg in 10 healthy subjects. The diuretic effect, in terms of urine flow and @entity1372 ion excretion in the 6 h after administration, was also less in @entity1 than in healthy subjects. This was ascribed to the lower bioavailability of @entity1483 in @entity1 , based on the urinary recovery of unchanged drug, and not to a lower level of response to @entity1483 than in healthy subjects. The mean absolute bioavailability of @entity1483 in 6 @entity1 was 41.3% and 63.4%, respectively, calculated from unchanged drug and total drug (unchanged plus glucuronide conjugate). Approximately 53.9% of the dose of @entity1483 was excreted as the glucuronide conjugate after oral administration, and 34.2% after i.v. injection in the 6 @entity1 . In 3 of the 6 @entity1 studied, a distinct first-pass effect for glucuronidation of @entity1483 was observed after oral administration. In another study, the mean glucuronide fraction recovered in 24-h urine was 20.7% and 7.3% (p less than 0.01) in 38 @entity1 and 12 healthy subjects, respectively. The fraction in urine was not affected by changing the dose of @entity1483 from 20 to 120 mg. The lower bioavailability in @entity1 as compared to healthy subjects is ascribed to enhanced glucuronidation and incomplete drug absorption.
