Absolute bioavailability and stereoselective pharmacokinetics of doxepin

  title={Absolute bioavailability and stereoselective pharmacokinetics of doxepin},
  author={J.-H. Yan and John W. Hubbard and Gordon Mckay and Elarien D. Korchinski and Kamal K. Midha},
  pages={615 - 623}
1. Commercial doxepin contains geometric isomers in the proportions Z : E = 15:85. Z -doxepin and its metabolite Z - N -desmethyldoxepin are both active antidepressants, whereas the corresponding E -isomers are less active therapeutically. 2. The present pharmacokinetic study was a balanced, randomized, two-treatment, two-period, two-sequence crossover design in which 12 healthy male volunteers were given single doses of commercial doxepin intravenously and orally on two occasions separated by… 

The Role of Metabolites in Bioequivalence

The principles of pharmacokinetic principles based on estimates of intrinsic clearance after oral administration of the parent drug were applied to four bioequivalence studies from the archives, in which the parentDrug and at least one metabolite were monitored.

Mechanistic Approaches to Volume of Distribution Predictions: Understanding the Processes

Generic distribution processes were identified as lipid partitioning and dissolution where the former is higher for lipophilic unionised drugs and the latter for acidic drugs.

Physiological scaling factors and mechanistic models for prediction of renal clearance from in vitro data

A comprehensive literature analysis of quantitative physiological data to inform renal IVIVE scaling factors and systems parameters relevant for physiologically based pharmacokinetic (PBPK) kidney models was performed and a novel 5-compartment model for prediction of tubular re absorption and CLR from Caco-2 apparent permeability data was developed.

Characterization of the membrane transporter OATP1A2 activity towards different classes of drugs

Development of an in vitro system for the functional study of the OATP1A2 transporter in the uptake of statins and its applications in medicine and oncology is described.

Markers of Individual Drug Metabolism: Towards the Development of a Personalized Antidepressant Prescription.

Recent studies have yielded promising results regarding the potential benefits of determining drug metabolism variability which might encourage additional large-scale prospective systematic studies be set up to assess the relevance of this approach in everyday practice.



Stereoselective pharmacokinetics of doxepin isomers

Results for total doxepin showed wide intersubject variation in all pharmacokinetic parameters except tmax and Cmax and the areas under the plasma concentration versus time curves (AUC) of cis-N-desmethyldoxepin were significantly higher than those of the corresponding trans-isomer.

Single dose pharmacokinetics of doxepin in healthy volunteers.

The pharmacokinetics of orally administered doxepin (50 mg) was studied in 8 healthy volunteers and 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.

Pharmacokinetic evaluation of two doxepin products.

The results of this study demonstrate that the two formulations of doxepin HCl are bioequivalent and would be expected to have similar clinical efficacy.

Geometric isomerization of doxepin during its N-demethylation in humans.

Findings indicate that isomerization occurs during the N-demethylation of doxepin, possibly involving the formation of an intermediate in which the exocyclic double bond is hydrated and then subseqently dehydrated.

Distribution and metabolism of doxepin.

  • D. Hobbs
  • Chemistry, Biology
    Biochemical pharmacology
  • 1969

Plasma levels of the cis- and trans-isomers of doxepin and desmethyldoxepin after administration of doxepin to patients.

In depressed patients treated with doxepin (Sinequan), a 15:85% mixture of cis- and trans-isomers, plasma levels of the cis- and trans-forms of doxepin and desmethyldoxepin were measured using a

Cis‐ and Trans‐Isomers of Doxepin and Desmethyldoxepin in the Plasma of Depressed Patients Treated with Doxepin

It is found that significantly higher levels of desmethyldoxepin and of total drug are detected in plasma when the two isomers are separated and measured by method 2, and it is suggested that in future studies correlating plasma levels and the clinical effects of doxepin, both the cis- and trans-isomers of doXepin be determined.

Stereoselective and simultaneous measurement of cis- and trans-isomers of doxepin and N-desmethyldoxepin in plasma or urine by high-performance liquid chromatography.

Multiple‐dose doxepin kinetics in depressed patients

The concentration‐response curve indicated strong correlation between total DOX concentration (DOX + DMD) and antidepressant effect (r2 = 0.76) and stable‐state concentrations of DOX and DMD were reached within 2 wk of beginning DOX dosing.

High-performance liquid chromatographic determination of trans-doxepin and desmethyldoxepin.

This HPLC assay, employing a UV-detector and perazine as an internal standard, provides a very sensitive and selective determination in the low ng/ml range, well suited for quantitative determinations of plasma samples generated during clinical studies, eg.