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Metabolism and pharmacokinetics of dothiepin.
Author(s) -
Maguire KP,
Burrows GD,
Norman TR,
Scoggins BA
Publication year - 1981
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1981.tb01235.x
Subject(s) - pharmacokinetics , chemistry , half life , microgram , volume of distribution , absorption (acoustics) , metabolism , chromatography , medicine , biochemistry , in vitro , physics , acoustics
1 Seven healthy volunteers received a single oral dose of 75 mg dothiepin. Plasma concentrations of dothiepin were measured by gas chromatography‐mass fragmentography. 2 The plasma concentrations obtained were fitted to the equation Ct = Ae‐a(t‐tau) + Be‐beta(t‐tau) ‐ Ce‐ka(t‐tau). The mean peak concentration was 47(33‐71) microgram/l at 3(2‐5) h. Mean estimates were as follows: absorption half life 1.2(0.07‐ 3.0) h, distribution half‐life 2.6(1.1‐3.8) h, elimination half‐life 22(14‐40) h, apparent volume of distribution 45(20‐92) l/kg, and oral clearance 1.36(0.88‐1.8) l kg‐1 h‐1. 3 Blood concentrations of dothiepin were measured in comparison in five of the volunteers. The mean blood/plasma ratio was 0.7(0.6‐0.8). 4 Plasma and blood concentrations of northiaden and blood concentrations of dothiepin S‐ oxide, two metabolites of dothiepin, were also measured. Dothiepin S‐ oxide was the major metabolic reaching a peak level of 81(34‐150) microgram/l at 5(4‐6) h. In comparison, northiaden reached a peak concentration of only 10 (3‐21) microgram/l at 5 (4‐9) h. The mean half‐ life of elimination of dothiepin S‐oxide was 19 (13‐35) h while that for northiaden was 33 (22‐60) h.