Document Detail

Effect of aging on the pharmacokinetics of acebutolol enantiomers.
MedLine Citation:
PMID:  1613125     Owner:  NLM     Status:  MEDLINE    
Acebutolol (AC) is a chiral beta-blocker that is metabolized to an equipotent chiral metabolite, diacetolol (DC). A stereoselective disposition of AC and DC enantiomers has recently been reported in young healthy subjects. As many physiologic properties affecting drug disposition are progressively altered with increasing age, the effect of aging on the pharmacokinetics of AC and DC enantiomers were investigated in nine subjects ranging from 60 to 75 years after administration of an oral 200-mg dose of racemic AC. Increasing age resulted in a significant prolongation of the elimination t1/2s of R- (r = 0.913) and S-DC (r = 0.811). Also, the S:R ratios of AC urinary excretion (sigma Xu) of enantiomers was significantly correlated with age (r = 0.677). Contribution of declining renal function to age-associated pharmacokinetics changes was subsequently examined. Renal clearance and cumulative urinary excretion of both AC and DC enantiomers were positively correlated with creatinine clearance. In addition, declining creatinine clearance was associated with a subsequent decline in the enantiomer S:R ratio of AC in plasma (AUC S:R, r = 0.807) and urine (sigma Xu S:R r = 0.807). Similarly, a progressive decline in the S:R ratio of DC collected in urine was evident (r = 0.689). Age-related changes in the enantiomers ratios may suggest that an active stereoselective pathway such as renal tubular secretion or nonrenal excretion may be affected in the elderly.
M Piquette-Miller; R T Foster; C T Kappagoda; F Jamali
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Journal of clinical pharmacology     Volume:  32     ISSN:  0091-2700     ISO Abbreviation:  J Clin Pharmacol     Publication Date:  1992 Feb 
Date Detail:
Created Date:  1992-07-30     Completed Date:  1992-07-30     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0366372     Medline TA:  J Clin Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  148-56     Citation Subset:  IM    
Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
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MeSH Terms
Acebutolol / analogs & derivatives*,  pharmacokinetics*
Aging / metabolism*
Blood Proteins / metabolism
Kidney / metabolism
Middle Aged
Protein Binding
Reg. No./Substance:
0/Blood Proteins; 28197-69-5/diacetolol; 37517-30-9/Acebutolol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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