| Autor: |
Cunningham, J., Bullen, M., Price Evans, D. |
| Zdroj: |
European Journal of Clinical Pharmacology; 1974, Vol. 7 Issue 6, p461-466, 6p |
| Abstrakt: |
Acetanilide and diphenylhydantoin have a similar first stage biotransformation in that both are oxidized in the para position of the benzene ring incorporated in each of the two molecules. The elimination of acetanilide from the plasma was studied in thirty healthy volunteer subjects following a single oral dose of 50 mg per kg metabolically active mass (MAM = weight to the power of 0.7). Plasma clearance values varied from 12.4 to 25.11 per hour. A dose of 5 mg diphenylhydantoin sodium (DPH) per kg MAM was then given thrice daily for 13 days to the same volunteers. The steady state plasma concentrations of DPH varied from 3.4 to 19.6 µg per ml. Statistically significant correlation was demonstrated between plasma acetanilide clearance and DPH clearance ( r=+0.4984). This finding suggests either a common enzyme acceptor or a common rate-limiting step in the metabolism of the two drugs. It is possible that the pharmacokinetics of other widely used drugs known to be oxidized, especially phenylbutazone, may also be correlated with the kinetics of acetanilide and of DPH. If this were so, then certain individuals might be at a relatively high risk (due to drug accumulation) of developing adverse effects from drugs metabolized mainly by oxidation, and certain other individuals who metabolize these compounds at a fast rate are likely not to derive therapeutic benefit. A single dose study with simple measurement of acetanilide pharmacokinetics could be used to identify these groups. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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