Effect of age and gender on the pharmacokinetics of eprosartan.
OBJECTIVE
To compare the pharmacokinetics of eprosartan between young (18-45 years) and elderly (65 years) men and between young men and young, premenopausal women (18-45 years).


METHODS
Twenty-four subjects (eight subjects/group) received a single 200 mg eprosartan oral dose followed by serial blood sampling over 24 h.


RESULTS
Eprosartan was safe and well tolerated. There were no apparent differences in the pharmacokinetics of eprosartan between young females and young males or in the plasma protein binding of eprosartan (98%) for the three groups. On average, AUC (0,infinity) and Cmax values were approximately 2-fold higher in elderly men than young men [AUC (0,infinity) 95% CI: 1.22, 4.34; Cmax 95% CI: 0.98, 4.001. Similarly, unbound AUC (0,infinity) and Cmax values were, on average, approximately 2-fold higher in elderly men than young men [unbound AUC (0,infinity) 95% CI: 1.29, 4.44; unbound Cmax 95% CI: 1.02, 4.12]. tmax was delayed in the elderly men compared with young men, with a median difference of 2.5 h (95% CI: 1.00, 3.01 h).


CONCLUSIONS
No gender differences were observed in the pharmacokinetics of eprosartan. There were approximately two fold higher AUC and Cmax values for eprosartan observed in elderly men as compared with young men, most likely due to increased bioavailability of eprosartan in the elderly. Based on the excellent safety profile in the elderly in Phase III clinical trials (doses up to 1200 mg eprosartan) eprosartan can be safely administered to elderly hypertensive patients without an initial dose adjustment. Subsequently, the dose of eprosartan, as for other antihypertensive agents, may be individualized based on tolerability/response.
Drug Metabolism and Pharmacokinetics, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania, USA.
D M
DM
Tenero
D E
DE
Martin
A K
AK
Miller
B
B
Ilson
S C
SC
Boike
N
N
Zariffa
D K
DK
Jorkasky
D000179:Acrylates / Q000378:metabolism / Q000493:pharmacokinetics*; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D000959:Antihypertensive Agents / Q000378:metabolism / Q000493:pharmacokinetics*; D019540:Area Under Curve; D005260:Female; D006207:Half-Life; D006801:Humans; D007093:Imidazoles / Q000378:metabolism / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D017697:Premenopause; D011485:Protein Binding; D012737:Sex Factors; D013876:Thiophenes
D000179:Acrylates; D000959:Antihypertensive Agents; D007093:Imidazoles; D013876:Thiophenes; C068373:eprosartan