Influence of age, frailty and liver function on the pharmacokinetics of brofaromine

Zeeh, Joachim; Fuchs, L.; Bergmann, W.; Antonin, K.-H.; Degel, F.; Bieck, P.; Platt, D.

doi:10.1007/s002280050037

Cited by 3 publications

(3 citation statements)

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“…CYP1A2 is known to catalyze the oxidative metabolic activation of various procarcinogens such as aromatic amines and heterocyclic amines that cause colorectal or bladder cancers in humans 6 . In addition, CYP1A2 is known to be involved in the metabolism of various clinically useful drugs such as tacrine (used in patients with Alzheimer's disease) 7 and brofaromine (a selective inhibitor of monoamine oxidase A used in aged patients with mental disease) 8 . Long‐term use of these drugs in elderly patients with mental disease is known to produce hepatotoxicity.…”

mentioning

confidence: 99%

Effect of age and smoking on in vivo CYP1A2, flavin-containing monooxygenase, and xanthine oxidase activities in Koreans: Determination by caffeine metabolism

Chung

Kang

Park

et al. 2000

Clinical Pharmacology & Therapeutics

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Results of this caffeine metabolism study conducted with age- and gender-matched healthy Korean volunteers with and without smoking habits provided the baseline and the widely varying interindividual activities of CYP1A2, FMO, and xanthine oxidase in a Korean population. The results also suggested that drugs metabolized by CYP1A2 and FMO may require individualized dose adjustment according to the age and smoking habits of the subjects.

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confidence: 99%

Effect of age and smoking on in vivo CYP1A2, flavin-containing monooxygenase, and xanthine oxidase activities in Koreans: Determination by caffeine metabolism

Chung

Kang

Park

et al. 2000

Clinical Pharmacology & Therapeutics

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“…Investigations into the effect of age on in vivo activity of CYP1A2, 3A4, 2C9, 2C19 and 2D6 generally report decreases, 18 although not for all substrates. For example, CYP1A2 activity is reported as both unchanged 19,20 and decreased 21,22 with increasing age. Although it is not possible to attribute the effect of age on alosetron metabolism to a specific CYP enzyme, the latter finding is consistent with the results of this study.…”

Section: Discussionmentioning

confidence: 99%

Alosetron repeat dose pharmacokinetics, effects on enzyme activities, and influence of demographic factors

Koch¹,

Corrigan²,

Manzo³

et al. 2004

Aliment Pharmacol Ther

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SUMMARYAim: To assess the pharmacokinetics of alosetron, its effect on in vivo enzyme activities, and influence of demographic factors during repeated dosing. Methods: Thirty healthy men and women received 1 mg oral alosetron twice-daily for 29.5 days and a single oral dose of a metabolic probe cocktail before and on the last day of alosetron dosing. Serum alosetron concentrations were measured on days 1, 8, 15, 22 and 29. Probe-substrate and metabolite concentrations were measured after each cocktail dose. Results: Alosetron accumulation in serum was negligible. Exposure to alosetron did not alter probemetabolite/substrate ratios associated with CYP2C19, 2E1, 2C9, or 3A4 activity, but modestly decreased those associated with CYP1A2 and N-acetyltransferase activity. Systemic exposure to alosetron was higher in women, positively correlated with age and body mass index, and negatively correlated with CYP1A2 activity. Incidence of constipation was higher in women, but not associated with alosetron concentration. Conclusions: Single dose data can reliably predict the pharmacokinetics of alosetron after repeated doses. Alosetron exhibits limited potential for inhibition of cytochrome P450-mediated metabolism. Interindividual differences in alosetron pharmacokinetics associated with demographic factors may be related to strong dependence on metabolism by CYP1A2.

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“…A more comprehensive definition using markers of biological age could lead to improved comparability between studies. Such markers of old age and frailty may include liver volume, 5,35,36 renal clearance, and clearance of probe drugs, [37][38][39][40] as well as markers of systemic inflammation like Creactive protein, interleukin 6, and p16-INK4a. 41 DNA methylation patterns may correlate surprisingly closely with age, 42 but there are currently no data on the predictive power of these agespecific methylation patterns for age-related changes in PK.…”

Section: Defining Old Age and Frailtymentioning

confidence: 99%

Genomic Variation and Pharmacokinetics in Old Age: A Quantitative Review of Age‐ vs. Genotype‐Related Differences

Dücker

Brockmöller

2018

Clin Pharma and Therapeutics

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Older persons may particularly benefit from pharmacogenetic diagnostics, but there is little clinical evidence on that question. We quantitatively analyzed the effects of age and genotype in drugs with consensus on a therapeutically relevant impact of a genotype. Assuming additive effects of age and genotype, drugs may be classified in groups with different priorities to consider either age, or genotype, or both, in therapy. Particularly interesting were those studies specifically analyzing the age-by-genotype interaction.

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Influence of age, frailty and liver function on the pharmacokinetics of brofaromine

Abstract: Caffeine clearance, a simple, noninvasive test of CYP1A2 activity, is predictive of brofaromine clearance.

Cited by 3 publications

References 0 publications

Effect of age and smoking on in vivo CYP1A2, flavin-containing monooxygenase, and xanthine oxidase activities in Koreans: Determination by caffeine metabolism

Effect of age and smoking on in vivo CYP1A2, flavin-containing monooxygenase, and xanthine oxidase activities in Koreans: Determination by caffeine metabolism

Alosetron repeat dose pharmacokinetics, effects on enzyme activities, and influence of demographic factors

Genomic Variation and Pharmacokinetics in Old Age: A Quantitative Review of Age‐ vs. Genotype‐Related Differences

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