The pharmacokinetics of the alpha-blocking agent urapidil have been elucidated only in subjects with normal renal function. In the present study, BKU-15 (sustained-release capsules containing 15mg of urapidil) was administered for 7 consecutive days to 7 hypertensive patients with mild to moderate impairment of renal function. Treated were 3 males and 4 females between the ages of 24 to 74 years, and the dosing regimen was BKU-15 s. i. d. at 8: 00 a. m. on days 1 and 7, and b. i. d. at 8: 00 a. m. and 5: 00 p.m. on days 2 to 6.
The minimum plasma concentration of urapidil determined at 8: 00 a. m. stabilized by day 5, measuring 74.0±19.8ng/ml on day 7. The pharmacokinetic parameters calculated after administration on day 7 were as follows: Cmax 205.5±31.0ng/ml; Tmax 4.3±0.3hrs; kel 0.1±0.02/hr; t1/2 8.4±1.5hrs. The absorption rate constant, minimum plasma concentration, and Cmax of urapidil were comparable to the corresponding values in healthy subjects given a 2-fold dose (Ebihara et al.), whereas elimination was delayed by a factor of two.
A decrease in blood pressure was observed at 2 to 10 hours after administration of BKU-15. There was no significant change in heart rate. Two patients complained of hot flushes and throbbing in the temporal region, which might be related to the pharmacological effects of the drug. Severe nausea was noted in another patient.
It is thus considered that BKU-15 b. i. d, may be adequate as the initial dosage in treating hypertensive patients with impaired renal function.
