ISSN:0312-5963    

出版商:ADIS    

年代:1990

数据来源: ADIS

摘要:

Although there is considerable variation in the effect of age on drug biotransformation, the metabolism of many drugs is impaired in the elderly. Age-related physiological changes, such as a reduction in liver mass, hepatic metabolising enzyme activity, liver blood flow and alterations in plasma drug binding may account for the decreased elimination of some metabolised drugs in the elderly. It is difficult, however, to separate an effect of aging from a background of marked variation in the rate of metabolism due to factors such as individual metabolic phenotype, environmental influences, concomitant disease states and drug intake. The prevailing data suggest that initial doses of metabolised drugs should be reduced in older patients and then modified according to the clinical response. In most studies the elderly appear as responsive as young individuals to the effects of compounds which induce or inhibit the activity of cytochrome P450 isozymes. Concurrent use of other agents, which induce or inhibit drug metabolism, mandates dose adjustment as in younger patients.Many questions remain unanswered. For instance, limitations ofin vitrostudies prevent any firm conclusion about changes in hepatic drug metabolising enzyme activity in the elderly. With aging, some pathways of drug metabolism may be selectively affected, but this has not been adequately scrutinised. The possibility that metabolism of stereoisomers may be altered in the elderly has not been adequately tested. The effect of aging on the distribution of polymorphic drug metabolism phenotypes is still not established, despite potential implications for disease susceptibility and survival advantage.

ISSN:0312-5963    

出版商:ADIS    

年代:1990

数据来源: ADIS

摘要:

Interferons are a family of proteins shown to be effective in the treatment of viral (condylomata, acuminata) and neoplastic (hairy cell leukaemia and AIDS-related Kaposi's sarcoma) diseases. To date, the clinical utility of the interferons has been hampered by an incomplete understanding of their mechanism of action. However, there is supporting evidence that the route of administration, i.e. the pharmacokinetic behaviour, is an important treatment variable.The pharmacokinetics of interferons have been fairly well described. The decline in serum concentrations of interferon is rapid after intravenous administration. The volume of distribution approximates 20 to 60% of bodyweight. Work in animals suggests that the catabolism of interferons falls within the natural handling of proteins. Clearance values vary (4.8 to 48 L/h) across the family of interferons and probably reflect the natural internal digestion and turnover of these proteins. Terminal elimination half-lives range from 4 to 16 hours, 1 to 2 hours and 25 to 35 minutes for&agr;, &bgr;and &ggr;, respectively. Intramuscular and subcutaneous administration of interferons&agr;and&bgr;results in protracted but fairly good absorption: >80% for interferon-&agr;and 30 to 70% for interferon-&ggr;.Interferon therapy is associated with adverse events which are usually mild and reversible. Temporal relationships exist between the degree and duration of adverse effects and the route of administration. Attempts to relate inducible biochemical markers, such as 2′,5′-oligoadenylate synthetase activity, to dose or concentration have met with some success although alterations in these markers have not been shown to relate to clinical response. Interferons can reduce hepatic drug metabolism but further work is needed before a true assessment of clinical relevance can be made. Finally, antibodies to the interferons have been detected but the clinical relevance is still unknown.

ISSN:0312-5963    

出版商:ADIS    

年代:1990

数据来源: ADIS

摘要:

Part I of this article, which appeared in the previous issue of the Journal, considered the potential mechanisms of drug interactions with cyclosporin, and divided the interacting drugs into 2 categories. Drugs that decrease cyclosporin concentrations (e.g. anticonvulsants, rifampicin, etc.) were dealt with first; the authors then moved on to consider the second category, those that increase cyclosporin concentration (macrolide antibiotics, azole antifungal drugs). Part II continues the survey of this category.

ISSN:0312-5963    

出版商:ADIS    

年代:1990

数据来源: ADIS

摘要:

Studies on the effects of age on the pharmacokinetics of alfentanil are inconclusive. A possible factor in explaining the differences between various studies could be the effect of gender. The authors studied the effects of age on the pharmacokinetics of alfentanil in female (n = 21) and male (n = 15) patients undergoing lower abdominal surgery under nitrous oxide alfentanil anaesthesia. There was a significant negative correlation (r = −0.79, p < 0.001) between plasma alfentanil clearance (CL) and age in women (<50y, median CL 24.84 L/h; > 50y, median CL 14.52 L/h), but not in men (<50y, median CL 19.44 L/h; >50y, median CL 16.2 L/h). The conclusion is drawn that the effects of age on the pharmacokinetics of alfentanil are gender-dependent.

ISSN:0312-5963    

出版商:ADIS    

年代:1990

数据来源: ADIS