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Doxepin kinetics
Author(s) -
Ziegler Vincent E.,
Biggs John T.,
Wylie Laurence T.,
Rosen Samuel H.,
Hawf Donald J.,
Coryell William H.
Publication year - 1978
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt1978235573
Subject(s) - doxepin , chemistry , pharmacokinetics , volume of distribution , kinetics , metabolite , oral administration , half life , absorption (acoustics) , pharmacology , steady state (chemistry) , plasma concentration , medicine , biochemistry , physics , quantum mechanics , acoustics
The kinetics of doxepin (DOX) hydrochloride were studied in 7 volunteers after the oral administration of 75 mg. Peak plasma concentrations of DOX ranged from 8.8 to 45.8 ng/ml and were reached within 4 hr. The disappearance of DOX was biphasic and followed first‐order kinetics. The mean DOX half life (t ½ ) was 16.8 hr and in individuals ranged from 8.2 to 24.5 hr. The mean apparent volume of distribution was 20.2 L/kg and ranged from 9.1 to 33.3 L/kg. The estimated first‐pass metabolism of DOX ranged from 55% to 87% of the oral dose assuming complete absorption. Significant quantities of the metabolite desmethyldoxepin (DMD) were produced. Peak levels of DMD ranged from 4.8 to 14.5 ng/ml and were reached between 2 and 10 hr after administration. The mean tl ½ of DMD was 51.3 hr and in individuals ranged from 33.2 to 80.7 hr. There was no correlation between the DOX and DMD t ½ s. The amount of DMD produced correlated with the plasma concentration of DOX and appears to explain the correlation between the steady‐state concentrations of DOX and DMD in patients given DOX.