[Interindividual variability in drug metabolism, especially in the elderly. Underlying mechanisms and a possible solution].
The metabolism of a drug reveals a large interindividual variability, which might be attributed to large interindividual differences in the activity of cytochrome P-450 isoenzymes. However, it is difficult to determine this activity in the intact animal or man. With the help of antipyrine, a measure for this activity in man might be possible. Antipyrine is metabolized via 3 metabolic pathways, which are regulated by different isoenzymes of cyt.P-450. In addition, the ratio 6 beta-hydroxycortisol(6 beta-OHF)/17-hydroxycorticosteroids(17-OHCS) in the urine is a measure for the activity of another cyt.P-450 isoenzyme, namely NIF. A correlation between the formation rates of the antipyrine metabolites, hydroxymethylantipyrine and hydroxyantipyrine (OHA) and the clearance of hexobarbital and theophylline, respectively, has been observed. In young volunteers, a good correlation between the formation rate of OHA and the clearance of theophylline have also been found. It must be investigated whether these correlations can also be observed if one smokes, consumes alcohol, keeps diet, takes several drugs, is young or old or is a male or female. If this is the case, the metabolism is predictable, the dose can be adapted and adverse reactions can be prevented, especially in the aged.
van Bezooijen
C F
CF
Instituut voor Experimentele Gerontologie-TNO, Rijswijk.
D000368:Aged; D000375:Aging / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*
D007527:Isoenzymes; D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System
Interindividuele variabiliteit in geneesmiddelenverwerking met name bij ouderen. Onderliggende mechanismen en een mogelijke aanpak.