CYP2C18
Cytochrome P450 2C18 precursor (EC 1.14.14.1) (CYPIIC18) (Cytochrome P450-6b/29c)
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Cytochrome P450 enzymes, especially the CYP2C subfamily, are involved in the generation of reactive oxygen species and are regarded as susceptibility factors for age-related diseases. Furthermore, the CYP2C-encoding genes are known to be highly polymorphic, with a number of variants leading to changes in enzyme activity. These observations prompted us to investigate whether allelic variation in the CYP2C-encoding genes was associated with human longevity. In a comprehensive haplotype tagging approach, we genotyped 56 single nucleotide polymorphisms located in the CYP2C gene family (CYP2C8, CYP2C9, CYP2C18, and CYP2C19) in our extensive collection of 1,384 long-lived individuals (centenarians and nonagenarians) and 945 younger controls. None of the tested single nucleotide polymorphisms showed a significant association with the longevity phenotype at the allele, genotype, or haplotype level. These results suggest that there is no notable influence of sequence variation in the CYP2C genes on longevity in the examined German population.
MeSH Terms
- Aged, 80 and over
- Aryl Hydrocarbon Hydroxylases
- Cytochrome P-450 CYP2C19
- Cytochrome P-450 CYP2C8
- Cytochrome P-450 CYP2C9
- Cytochrome P-450 Enzyme System
- Female
- Genetic Association Studies
- Genetic Predisposition to Disease
- Genetic Variation
- Germany
- Humans
- Linkage Disequilibrium
- Longevity
- Male
- Polymorphism, Single Nucleotide
Lansoprazole, a benzimidazole derivative with antisecretory and antiulcer activities, inhibits the acid pump activity at the final stage of the enzyme process and therefore reduces the acid secretion of parietal cells. Lansoprazole is converted to active metabolites in the acid environment of these cells. It is rapidly absorbed from a gastric acid-resistant formulation and is approximately 97% bound in human plasma. Single dose pharmacokinetics of lansoprazole appear to be linear over the range from 15 to 60mg. Food and time of dose influence absorption after single doses, but do not modify the antisecretory effect of multiple doses. Lansoprazole is extensively metabolised following oral administration into sulphone and 5-hydroxylated metabolites by the cytochrome P450 enzymes CYP3A4 and CYP2C18. Two other metabolites have been identified in plasma: sulphide and hydroxylated sulphone. Mean plasma elimination half-life (t1/2) is between 1.3 and 2.1 hours in healthy volunteers. 15 to 23% of the total dose is found in urine as free and conjugated hydroxylated metabolites, while unchanged lansoprazole is not detected. The pharmacokinetic profile of the drug is not modified by multiple administration. In healthy elderly volunteers, area under the plasma concentration-time curve (AUC) and t1/2 are significantly greater after single administration occurs to the same extent as in young volunteers. Renal failure has no influence on the pharmacokinetics of lansoprazole, but severe hepatic failure causes a significant decrease in clearance and an increase in the AUC and t1/2 of lansoprazole. This is accompanied by modifications in the AUC of metabolites, but severe hepatic failure has minimal effect on accumulation of the drug after multiple administration. The pharmacokinetics of lansoprazole in patients with acid-related disorders do not differ from those in healthy volunteers. Studies of interactions of lansoprazole with warfarin, prednisone, theophylline, phenazone (antipyrine), diazepam, phenytoin and oral contraceptives suggest minimal risk of any clinically significant interaction.
MeSH Terms
- 2-Pyridinylmethylsulfinylbenzimidazoles
- Aging
- Anti-Ulcer Agents
- Drug Interactions
- Gastrointestinal Diseases
- Humans
- Lansoprazole
- Liver Failure
- Omeprazole
- Renal Insufficiency