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Age-associated stereoselective alterations in hexobarbital metabolism. 1988

M H Chandler, and S R Scott, and R A Blouin
Drug Product Evaluation Unit, University of Kentucky College of Pharmacy, Lexington 40536-0082.

This clinical investigation was designed to study the influence of age on stereoselective drug disposition using hexobarbital as a model marker. The disposition of hexobarbital enantiomers was investigated in 10 young and 10 elderly, healthy male volunteers. Mean oral clearance (+/- SD) of d-hexobarbital (1.9 +/- 0.5 vs. 1.7 +/- 0.3 ml/min/kg; P greater than 0.05) did not differ significantly between the young and elderly subjects, respectively. However, despite wide intersubject variability, l-hexobarbital mean oral clearance (+/- SD) was approximately twofold greater in the young than in the elderly subjects (16.9 +/- 11.9 vs. 8.2 +/- 3.2 ml/min/kg; P less than 0.05). This resulted in a significantly greater enantiomeric oral clearance ratio in the young when compared with the elderly subjects (8.3 +/- 3.4 vs. 4.7 +/- 1.4; P less than 0.01). No significant difference (P greater than 0.05) in pharmacologic response after hexobarbital administration was found between the two groups. Demonstration of an age-related preferential decline in metabolism of one enantiomer over another has not been reported previously for any racemic drug in animals or humans.

UI MeSH Term Description Entries
D008297 Male Males
D011597 Psychomotor Performance The coordination of a sensory or ideational (cognitive) process and a motor activity. Perceptual Motor Performance,Sensory Motor Performance,Visual Motor Coordination,Coordination, Visual Motor,Coordinations, Visual Motor,Motor Coordination, Visual,Motor Coordinations, Visual,Motor Performance, Perceptual,Motor Performance, Sensory,Motor Performances, Perceptual,Motor Performances, Sensory,Perceptual Motor Performances,Performance, Perceptual Motor,Performance, Psychomotor,Performance, Sensory Motor,Performances, Perceptual Motor,Performances, Psychomotor,Performances, Sensory Motor,Psychomotor Performances,Sensory Motor Performances,Visual Motor Coordinations
D006591 Hexobarbital A barbiturate that is effective as a hypnotic and sedative. Evipan,Hexenal,Hexobarbitone,Sodium Hexobarbital,Hexobarbital, Sodium
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly
D000375 Aging The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time. Senescence,Aging, Biological,Biological Aging
D013237 Stereoisomerism The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed) Molecular Stereochemistry,Stereoisomers,Stereochemistry, Molecular,Stereoisomer

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