Anticonvulsant therapy in aged patients. Clinical pharmacokinetic considerations. 1997

I Bernus, and R G Dickinson, and W D Hooper, and M J Eadie
Conjoint Endocrine Laboratory, Royal Brisbane Hospital, Queensland, Australia. mortomr@citec.qld.gov.au

Alterations in drug disposition that occur with aging are now becoming widely recognised, and there is an increasing number of drugs for which the approach to therapy in elderly patients can be based on pharmacokinetic data. Both healthy aging and comorbid disease can alter the responsiveness of the body to drugs and to their absorption, distribution and elimination. Altered absorption in the elderly has not been documented after oral ingestion of any anticonvulsant drug. Increased adipose tissue in the elderly may raise the apparent volume of distribution (Vd) of lipid-soluble drugs. An increased Vd in the elderly has been shown for diazepam and clobazam, but not midazolam. The data are inconclusive for phenytoin and valproic acid (sodium valproate). The decreased plasma protein binding that often occurs in the elderly has few clinical consequences. The reduced liver function that to occur with aging seems to affect the elimination of drugs that are mainly cleared by oxidative metabolism [e.g. carbamazepine, phenytoin and phenobarbital (phenobarbitone)]. Reduced clearances for methylphenobarbital (methylphenobarbitone), diazepam, midazolam and clobazam occur in elderly men, but not in women. The reduced renal function that is seen in old age affects the disposition of drugs that are eliminated mainly by direct renal excretion. Thus. the clearances of vigabatrin and gabapentin correlate with creatinine clearance. Such considerations may help guide anticonvulsant dosage in the elderly.

UI MeSH Term Description Entries
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D002986 Clinical Trials as Topic Works about pre-planned studies of the safety, efficacy, or optimum dosage schedule (if appropriate) of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects. This concept includes clinical trials conducted both in the U.S. and in other countries. Clinical Trial as Topic
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000042 Absorption The physical or physiological processes by which substances, tissue, cells, etc. take up or take in other substances or energy.
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

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