Single and Multiple Dose Pharmacokinetics of a Sustained-Release Formulation of Bunazosin (E1015) in Healthy Young and Elderly Volunteers
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The results of 1 multiple dose and 2 single dose pharmacokinetic studies of sustained-release bunazosin (Bunazosin Retard®) 6mg in healthy elderly (n = 47) and healthy young (n = 12) volunteers are suggestive of an age-related difference in the drug’s disposition. Area under the concentration-time curve (AUC) and peak plasma concentration (Cmax) values were significantly higher [AUC: x 1.9 (male) and x 1.9 (female); Cmax x 2.0 (male) and x 1.9 (female)] in the elderly than in their younger counterparts. This difference in AUC0-48h and Cmax values appeared to be due to reduced bunazosin clearance in the elderly. Steady-state plasma bunazosin concentrations in elderly volunteers (n = 12) were achieved 9 days after initiating multiple oral dose administration of Bunazosin Retard® 6mg once daily. There was no evidence of further bunazosin accumulation after 8 days of oral dose administration.
Bunazosin Retard® 6 mg/day caused moderate to marked reductions in supine and standing systolic and diastolic blood pressures (≈ 18/15mm Hg and 32/15mm Hg, respectively, at 6 to 8 hours postdose) and a modest increase in standing heart rate (≈ 15 beats/min). This hypotensive effect was more pronounced in the elderly.
KeywordsDrug Invest Elderly Volunteer Sparteine High Performance Liquid Chro Mephenytoin
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