Plasma levels of the enantiomers of thioridazine, thioridazine 2‐sulfoxide, thioridazine 2‐sulfone, and thioridazine 5‐sulfoxide in poor and extensive metabolizers of dextromethorphan and mephenytoin

@article{Eap1996PlasmaLO,
  title={Plasma levels of the enantiomers of thioridazine, thioridazine 2‐sulfoxide, thioridazine 2‐sulfone, and thioridazine 5‐sulfoxide in poor and extensive metabolizers of dextromethorphan and mephenytoin},
  author={Chin B. Eap and Theodor W. Guentert and Martina Sch{\"a}ublin‐Loidl and Max Stabl and Liliane Koeb and Kerry Powell and Pierre Baumann},
  journal={Clinical Pharmacology \& Therapeutics},
  year={1996},
  volume={59}
}

Steady state plasma levels of the enantiomers of trimipramine and of its metabolites in CYP2D6-, CYP2C19- and CYP3A4/5-phenotyped patients.

TLDR
A stereoselectivity in the metabolism of TRI has been found, with a preferential N-demethylation of (D)-TRI and a preferential hydroxylation of L-TRI, and CYP2D6 appears to be involved in the demethylation pathway.

Thioridazine steady-state plasma concentrations are influenced by tobacco smoking and CYP2D6, but not by the CYP2C9 genotype

TLDR
The results show that the plasma concentrations of thioridazine and its metabolites are influenced by tobacco smoking and the CYP2D6 genotype, and support the dose-dependent inhibition of CYP 2D6 by thIORidazine.

Factors Affecting Drug Concentrations and QT Interval During Thioridazine Therapy

TLDR
Plasma concentrations of thioridazine are influenced by age, smoking, and CYP2D6 genotype, but CYP3C19 genotype does not appear to influence on‐treatment QTc interval.

Use of the mesoridazine/thioridazine ratio as a marker for CYP2D6 enzyme activity.

TLDR
It is suggested that the measurement of thioridazine and its metabolite might be a useful tool to assess CYP2D6 activity during treatment, because potentially dangerous metabolic interactions may occur.

Racemization and degradation of thioridazine and thioridazine 2-sulfone in human plasma and aqueous solutions.

We present two methods for the enantioselective analysis of thioridazine (THD) and thioridazine 2-sulfone (THD 2-SO(2)) in human plasma based on liquid-liquid extraction with diethyl ether and chiral

Pharmacokinetic Drug Interaction Potential of Risperidone With Cytochrome P450 Isozymes as Assessed by the Dextromethorphan, the Caffeine, and the Mephenytoin Test

TLDR
Risperidone at dosages between 2 and 6 mg/d does not appear to significantly inhibit CYP1A2 and CYP2C19 in vivo and can be considered a weak in vivo CYP 2D6 inhibitor, as this increase is modest and none of the eight patients was changed from an extensive to a poor metabolizer.

Steady state concentrations of the enantiomers of mianserin and desmethylmianserin in poor and in homozygous and heterozygous extensive metabolizers of debrisoquine.

TLDR
The results suggest that the debrisoquine genotype has only a moderate influence on the steady state concentrations of the enantiomers of mianserin and desmethylmianser in a single-dose study with poor and extensive metabolizers of debrisoquines.

Degradation and configurational changes of thioridazine 2-sulfoxide.

Comparison of the Effects of Thioridazine and Mesoridazine on the QT Interval in Healthy Adults After Single Oral Doses

TLDR
Thioridazine and mesoridazine are associated with similar effects on the QTc interval and the area under the effect–time curve over 8 h following drug administration was similar between the two drugs.
...

References

SHOWING 1-10 OF 35 REFERENCES

Plasma levels of thioridazine and metabolites are influenced by the debrisoquin hydroxylation phenotype

TLDR
The formation of mesoridazine from thioridazine and the 4‐hydroxylation of debrisoquin seem to be catalyzed by the same enzyme, whereas the formation of thIORidazine ring‐sulphoxide is probably formed mainly by another enzyme.

Enantioselective amitriptyline metabolism in patients phenotyped for two cytochrome P450 isozymes

In 26 hospitalized patients with depression, a combined pharmacogenetic test with dextromethorphan, a substrate of cytochrome P450IID6, and mephenytoin, the S‐form of which is hydroxylated by a

Light‐Induced Racemization: Artifacts in the Analysis of the Diastereoisomeric Pairs of Thioridazine 5‐Sulfoxide in the Plasma and Urine of Patients Treated with Thioridazine

TLDR
Because it is known that the ring sulfoxide contributes to the cardiotoxicity of the drug even more potently than the parent compound does, these results justify further studies to determine whether there is stereoselectivity in the cardiotsoxicity of THD 5-SO.

Dextromethorphan and Mephenytoin Phenotyping of Patients Treated with Thioridazine or Amitriptyline

TLDR
The dextromethorphan pharmacogenetic test can be used for clinical purposes, but to avoid artefacts it should be done after a washout period, especially after treatment with thioridazine; testing with mephenytoin is less likely to be influenced by thIORidazine or amitriptyline.

Thioridazine toxicity--an experimental cardiovascular study of thioridazine and its major metabolites in overdose.

TLDR
Although all four drugs increased the QRS and Q-Tc interval, ventricular arrhythmias and "torsades de pointes" were seen only in dogs receiving the ring sulfoxide.

Artifacts in the analysis of thioridazine and other neuroleptics.

The mephenytoin oxidation polymorphism is partially responsible for the N‐demethylation of imipramine

TLDR
In conclusion, this and an earlier study show that the oxidation of imipramine is mediated by means of two different polymorphic P450 isozymes, 2‐hydroxylation by way of the sparteine oxygenase (P450IID6) and demethylation by Way of the mephenytoin oxygen enzyme (P 450IIC8).

Greater potency of mesoridazine and sulforidazine compared with the parent compound, thioridazine, on striatal dopamine autoreceptors.

TLDR
Results indicate that thioridazine and its two clinically active metabolites can block striatal DA autoreceptors involved in modulating DA release, consistent with the hypothesis that a major part of the pharmacologic responses to thIORidazine may be a consequence of its metabolism to active compounds.