Single Dose Pharmacokinetics of Doxepin in Healthy Volunteers

Abstract

Abstraci:The pharmacokinetics of orally administered doxepin (50 mg) was studied in 8 healthy volunteers. Doxepin (DOX) and desmethyldoxepin (DDOX) concentrations in serum (or plasma) and red blood cells (RBCs) were measured by radioimmunoassay. Peak serum concentrations of DOX were observed at 1-2 hours and they ranged between 59.1-107.4 nmol/l. DOX disappearance was biphasic with a mean distribution halflife of 2.0 hrs and elimination half-life of 17.9 hrs. The mean total apparent volume of distribution was 22.7 l/kg and plasma clearance 0.93 I/hr/kg. The estimated mean first-pass metabolism of DOX was 71 % assuming complete absorption. Peak DDOX concentrations were observed at 1-6 hours and they ranged between 35.0-117.8 nmol/l. DDOX elimination was monophasic with a mean apparent half-life of 28.5 hours. Equilibrium dialysis gave a mean protein binding of 75.5% for DOX and 76.0% for DDOX. A highly time dependent and interindividually variable RBC/plasma concentration ratio was observed for both substances. Initially the plasma concentrations were 3-4 times higher than the respective RBC concentrations, but at later time points more DOX and DDOX could be found from the RBCs than from plasma. The major reason for this seemed to be a slower elimination of both drugs from the erythrocytes than from plasma.

Human UDP-Glucuronosyltransferase (UGT) 2B10: Validation of Cotinine as a Selective Probe Substrate, Inhibition by UGT Enzyme-Selective Inhibitors and Antidepressant and Antipsychotic Drugs, and Structural Determinants of Enzyme Inhibition

“…Assuming linear kinetics, the C max expected for a single 150 mg dose of amitriptyline is 0.45 mM. Doxepin (50 mg dose): mean C max 0.29 mM (Virtanen et al, 1980), fu 0.79 (Faulkner et al, 1983). Again, assuming linear kinetics, the C max expected for a single 150 mg dose of doxepin is 0.87 mM.…”

Characterization of Novel Selective H1-Antihistamines for Clinical Evaluation in the Treatment of Insomnia

“…16 Single dose studies have indicated sedative effects lasting up to 5 h, 17 consistent with the reported half-life of racemic dimethindene (∼5 h). 18 More recently, doxepin, a potent antihistamine with elimination half-life of 18 h, 19 has shown sleep maintenance effects lasting up to 8 h at low doses with no next day residual effects. 15 While 1a exhibited less than ideal duration of action for the treatment of insomnia, the compound represented an excellent starting point to identify novel analogues for clinical evaluation that retained receptor selectivity with potentially improved pharmacokinetic profile.…”