Effect of the novel anxiolytic drug deramciclane on the pharmacokinetics and pharmacodynamics of the CYP3A4 probe drug buspirone

@article{Laine2003EffectOT,
  title={Effect of the novel anxiolytic drug deramciclane on the pharmacokinetics and pharmacodynamics of the CYP3A4 probe drug buspirone},
  author={Kari Laine and Outi Ahokoski and Risto K. Huupponen and Jutta H{\"a}nninen and Sanna Palovaara and Jori O. Ruuskanen and Harry Bj{\"o}rklund and Markku I. Anttila and Juha Rouru},
  journal={European Journal of Clinical Pharmacology},
  year={2003},
  volume={59},
  pages={761-766}
}
  • K. Laine, O. Ahokoski, J. Rouru
  • Published 18 October 2003
  • Biology, Medicine, Psychology
  • European Journal of Clinical Pharmacology
RationalePreliminary in vitro findings indicated that the novel anxiolytic drug, deramciclane is a substrate for the cytochrome P450 (CYP) 3A4 isoenzyme. Moreover, its co-administration with buspirone, another anxiolytic drug, is likely in clinical practice.ObjectivesThe primary objective of the present study was to evaluate the in vivo effects of deramciclane on CYP3A4 activity as measured by buspirone pharmacokinetics. The secondary objective was to study the possible pharmacodynamic… 

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CYTOCHROME P 450 3 A-MEDIATED METABOLISM OF BUSPIRONE IN HUMAN LIVER MICROSOMES

TLDR
CYP3A, mostly likely CYP3A4, is primarily responsible for the metabolism of buspirone in HLMs, and it is suggested that urinary excretion is the major elimination pathway in humans, accounting for 60% of the total oral dose of [C]buspirone.

CYTOCHROME P450 3A-MEDIATED METABOLISM OF BUSPIRONE IN HUMAN LIVER MICROSOMES

TLDR
The metabolism rates of buspirone in CYP2D6 poor-metabolizer genotype HLMs were comparable to those in pooled HLMs, and data suggest that CYP3A, mostly likely CYP 3A4, is primarily responsible for the metabolism of bus Pirone in HLMs.

Evaluation of Recombinant Cytochrome P450 Enzymes as an in Vitro System for Metabolic Clearance Predictions

TLDR
Recombinant enzymes demonstrated improved prediction reliability relative to HLMs and hepatocytes, and the most reliable correlations in terms of lowest bias and highest precision were observed by comparing in vivo CLint, calculated using the parallel-tube model and incorporating fraction unbound in blood.

CYP 2 D 6 CATALYZES 5-HYDROXYLATION OF 1-( 2-PYRIMIDINYL )-PIPERAZINE , AN ACTIVE METABOLITE OF SEVERAL PSYCHOACTIVE DRUGS , IN HUMAN LIVER MICROSOMES

TLDR
Results indicate that polymorphic CYP2D6 is responsible for the conversion of 1-PP to HO-1-PP, a major urinary metabolite resulting from the N-dealkylation of several antidepressant/anxiolytic 5-HT1A agonists including buspirone.

CYP2D6 CATALYZES 5-HYDROXYLATION OF 1-(2-PYRIMIDINYL)-PIPERAZINE, AN ACTIVE METABOLITE OF SEVERAL PSYCHOACTIVE DRUGS, IN HUMAN LIVER MICROSOMES

TLDR
Results indicate that polymorphic CYP2D6 is responsible for the conversion of 1-PP to HO-1-PP, the major metabolite in the human circulation and in rat brains following oral administration of buspirone.

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