Influence of Age on the Pharmacokinetics of Alfentanil

Lemmens, Harry J. M.; Bovill, J. G.; Hennis, P. J.; Burm, A. G. L.

doi:10.1097/00000542-198809010-00629

Cited by 11 publications

(14 citation statements)

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“…found that gender did not appear to influence the clearance of nifedipine [16]. Contradictory results have been observed in alfentanil metabolism in relation to gender [17, 18]. Some studies failed to detect a significant gender difference in CYP3A4 concentrations in human liver microsomes and thus do not support the notion of a gender difference in CYP3A4 activity [8].…”

Section: Discussionmentioning

confidence: 99%

The distribution and gender difference of CYP3A activity in Chinese subjects

Zhu

Liu

Chen

et al. 2003

Brit J Clinical Pharma

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Aims To investigate the distribution of CYP3A activity in the Chinese population, and to test for gender-related differences in CYP3A activity. Methods Using midazolam as a probe drug, CYP3A activity in 202 Chinese healthy subjects (104 men) was measured by plasma 1 ¢ -hydroxymidazolam:midazolam (1 ¢ -OH-MDZ:MDZ) ratio at 1 h after oral administration of 7.5 mg midazolam. The different phases of the menstrual cycle including preovulatory, ovulatory and luteal phases of 66 women phenotyped with midazolam were recorded. The concentrations of 1 ¢ -OH-MDZ and MDZ in plasma were measured by HPLC Results A 13-fold variation of CYP3A activity (log1 ¢ -OH-MDZ:MDZ: range -0.949-0.203) was shown. The CYP3A activity was normally distributed as indicated by the frequency distribution histogram, the probit plot and the KolmogorovSmirnov test ( P > 0.05). The CYP3A activity of women was higher than that of men (median: -0.36 vs -0.43, P < 0.05; 95% CI for difference: -0.127, -0.012). There was a significant difference in CYP3A activity between the three phases of the menstrual cycle. The activity was highest in the preovulatory phase and decreased sequentially in the ovulatory and luteal phases ( P < 0.05). Conclusions A normal distribution of CYP3A activity was observed in the Chinese population. The CYP3A activity is higher in female subjects than in males. CYP3A activity differed across the phases of the menstrual cycle.

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Section: Discussionmentioning

confidence: 99%

The distribution and gender difference of CYP3A activity in Chinese subjects

Zhu

Liu

Chen

et al. 2003

Brit J Clinical Pharma

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“…Hepatic clearance of the highly extracted drug clomethiazole was 30% lower in 8 elderly (mean age 75 years) than in 6 young volunteers (mean age 23 years) [Nation et al 1976]. Lemens et al (1990) reported a significant negative correlation between age and plasma alfentanil clearance in women, but not in men. Lemens et al (1990) reported a significant negative correlation between age and plasma alfentanil clearance in women, but not in men.…”

Section: Hepatic Clearance and Blood F10wmentioning

confidence: 98%

Age-Related Changes in Hepatic Function

Woodhouse

Wynne

1992

Drugs & Aging

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An age-related decrease in the hepatic clearance of many drugs has been reported. Several mechanisms have been proposed, but only some are supported by hard evidence. Liver volume declines with age, as does hepatic blood flow--changes which may largely account for the reduced clearance of capacity- and flow-limited drugs, respectively. Age-related histological changes in the liver are minor and of uncertain significance; standard liver function tests do not change significantly with aging. There is, as yet, no direct evidence of a generalised fall in hepatic drug-metabolising enzyme activities in aging humans measured in vitro, but some in vivo studies suggest that certain very specific cytochrome P450 isoenzymes may be affected by aging, especially in men. Finally, there may be an age-related decline in the response to environmental influences.

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“…With alfentanil and cyclosporine there are reports on a higher clearance in women, but also reports on no difference (32)(33)(34)(35). Clearly higher metabolic rates were demonstrated for erythromycin in several studies (36)(37)(38)(39).…”

Section: Cyp3a4mentioning

confidence: 98%

Gender differences in pharmacokinetics

Gundert‐Remy

1996

European Journal of Drug Metabolism and Pharmacokinetics

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There is growing awareness that the underrepresentation of women in clinical trials and in particular in phase I studies may lead to incorrect handling of drugs. Despite the fact that investigations are not informed in a systematic way, there are a number of examples showing pharmacokinetic differences between gender. From the data actually presented, it can be concluded that the activity of CYP 3A4 activity as measured by elimination in vivo is higher in women compared to men. CYP isoenzymes other than CYP 3A4 seem to be more active in men than in woman, as are conjugation reactions, such as glucuronidation. The influence of changing hormonal levels during the lifetime of a woman has been looked at in some drugs but deserves further systematic investigation. The use of oral contraceptives can interfere with the metabolism of many drugs whereas, in pregnancy, the elimination of antiepileptics is increased which, without dose adjustment, leads to an increased number of seizures. The impacts of hormonal replacement therapy (HRT) on the pharmacokinetics of concomitantly given drugs is an important issue, as HRT is increasingly used, but more research is needed in this field.

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Influence of Age on the Pharmacokinetics of Alfentanil

Cited by 11 publications

References 0 publications

The distribution and gender difference of CYP3A activity in Chinese subjects

The distribution and gender difference of CYP3A activity in Chinese subjects

Age-Related Changes in Hepatic Function

Gender differences in pharmacokinetics

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