ICI 141,292 (epanolol)--pharmacokinetics after single and repeated oral administration in the elderly with moderate renal impairment.
The pharmacokinetics of ICI 141,292 (epanolol) were studies over 3 days after a single oral 200 mg dose and then over 24 h after 12 consecutive daily oral 200 mg doses in 16 elderly subjects (aged 65 to 94 years) with moderate renal impairment (mean creatinine clearance 33.2 ml.min-1). There was wide inter-individual variability in peak plasma ICI 141,292 concentrations (Cmax) but no significant difference was found between mean Cmax after a single dose (44.3 ng.ml-1) and after 12 doses (37.4 ng.ml-1). The mean observed time to peak plasma ICI 141,292 concentration (tmax) after a single dose (1.61 h) did not differ significantly from that after 12 doses (1.75 h). On several occasions an analytically significant second peak in ICI 141,292 plasma concentration was observed. Following the peak(s), the plasma concentrations declined biphasically and a mean terminal phase plasma half-life (t1/2) of 28.3 (range 10.2-84.8) h was calculated after a single dose. The inter-individual variability in the area under the plasma concentration-time curve to 24 h AUC (0-24) was 54 fold but there was no significant difference between AUC (0-24) after a single dose (mean 226.0 ng.h.ml-1) and AUC (0-24) after 12 consecutive doses of ICI 141,292 (mean 232.4 ng.h.ml-1). The results show that consecutive daily administration of 12 oral doses of ICI 141,292 (200 mg) does not result in significant accumulation of drug in elderly subjects with moderate renal impairment.
Laher
M S
MS
James Connolly Memorial Hospital, Dublin.
Crome
P
P
Rakhra
G S
GS
Ankier
S I
SI
Cockshott
I D
ID
D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000368:Aged; D000369:Aged, 80 and over; D044482:Benzeneacetamides; D003404:Creatinine / Q000097:blood; D005260:Female; D006207:Half-Life; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism*; D008297:Male; D011412:Propanolamines / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000319:Adrenergic beta-Antagonists; D044482:Benzeneacetamides; D011412:Propanolamines; C038616:epanolol; D003404:Creatinine