Oral, Intraperitoneal and Intravenous Pharmacokinetics of Deramciclane and its N‐desmethyl Metabolite in the Rat

@article{Nemes2000OralIA,
  title={Oral, Intraperitoneal and Intravenous Pharmacokinetics of Deramciclane and its N‐desmethyl Metabolite in the Rat},
  author={K. Nemes and M. Abermann and E. Bojti and G. Gr{\'e}zal and S. al-Behaisi and I. Klebovich},
  journal={Journal of Pharmacy and Pharmacology},
  year={2000},
  volume={52}
}
The pharmacokinetic properties of deramciclane fumarate (EGIS‐3886), a new potential anxiolitic agent, and its N‐desmethyl metabolite have been investigated in Wistar rats after 10 mg kg−1 deramciclane fumarate was administered orally, intraperitoneally or intravenously. 
Studies of the side chain cleavage of deramciclane in rats with radiolabelled compounds.
TLDR
It is postulated that the low rate of formation and elimination of the metabolite(s) (DMAE or DMG) indicates that, due to their endogenous nature, they can be incorporated into choline/acetylcholine or protein synthesis. Expand
Influence of food on the oral bioavailability of deramciclane from film-coated tablet in healthy male volunteers.
  • S. Drabant, K. Nemes, +8 authors I. Klebovich
  • Chemistry, Medicine
  • European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
  • 2004
TLDR
The 24 and 31% increase in C(max) and AUC(0-infinity) of deramciclane, respectively, under fed condition is modest and probably has no clinical significance since it is relatively small compared to the inter-individual variability of these parameters. Expand
Comparison of the effects of deramciclane, ritanserin and buspirone on extracellular dopamine and its metabolites in striatum and nucleus accumbens of freely moving rats.
TLDR
There is at least a 5-fold margin between the anxiolytic and neuroleptic doses of deramciclane in the rat, particularly in mesolimbic regions. Expand
BIOTRANSFORMATION OF DERAMCICLANE IN PRIMARY HEPATOCYTES OF RAT, MOUSE, RABBIT, DOG, AND HUMAN
TLDR
It was concluded that phase I metabolism in human liver cells seemed to be similar to the metabolism in the hepatocytes isolated from rat, and the rat model may be considered to be predictive for human metabolism of deramciclane. Expand
Determination of deramciclane and N-desmethylderamciclane in human plasma by liquid chromatography-tandem mass spectrometry using off-line robotic sample pretreatment.
TLDR
A rapid and highly sensitive LC-MS-MS method using deuterium-labelled internal standards was developed and evaluated for the simultaneous determination of deramciclane and its pharmacologically active metabolite and shows that samples can be assayed with acceptable accuracy and precision. Expand
Pre-systemic metabolism prevents in vivo antikinetoplastid activity of N1,N4-substituted 3,5-dinitro sulfanilamide, GB-II-150.
TLDR
Data indicate that GB-II-150 undergoes rapid and extensive first-pass metabolism, precluding the attainment of effective systemic drug concentrations and explaining the lack of in vivo antitrypanosomal activity of this compound. Expand
Intraperitoneal Route of Drug Administration: Should it Be Used in Experimental Animal Studies?
TLDR
It is concluded that IP administration of drugs in experimental studies involving rodents is a justifiable route for pharmacological and proof-of-concept studies where the goal is to evaluate the effect(s) of target engagement rather than properties of a drug formulation and/or its pharmacokinetics for clinical translation. Expand
In vitro simulation of food effect on dissolution of deramciclane film-coated tablets and correlation with in vivo data in healthy volunteers.
  • S. al-Behaisi, I. Antal, +4 authors I. Klebovich
  • Chemistry, Medicine
  • European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
  • 2002
TLDR
In vitro modelling of in vivo conditions might help provide a base for predicting in vivo drug behaviour and establish a linear relationship between logarithmic in vivo blood sampling time and in vitro dissolution time assigned to equal AUC(cum) ratios. Expand
Intraperitoneal delivery of platinum with in-situ crosslinkable hyaluronic acid gel for local therapy of ovarian cancer.
TLDR
Although several materials considered biocompatible and safe are used as drug carriers, they may have unwanted biological effects on the residual targets once the drug is exhausted; therefore, more attention should be paid to the selection of drug carriers. Expand
Intraperitoneal chemotherapy of ovarian cancer by hydrogel depot of paclitaxel nanocrystals.
TLDR
Results support the advantage of PNC over PPT, demonstrate the promise of a gel depot as an IP drug delivery system, and support the survival of tumor-bearing mice significantly better than Taxol. Expand
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References

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Receptor binding profile and anxiolytic‐type activity of deramciclane (EGIS‐3886) in animal models
The present series of experiments was done to characterize the properties of deramciclane, a new antiserotonergic drug, in both receptor binding studies in vitro and in a number of anxiolytic,Expand
Comparative pharmacokinetics of deramciclane in rat, dog, rabbit and man after the administration of a single oral dose of 3 mg kg-1
TLDR
The comparative pharmacokinetic study of deramciclane indicated an intensive biotransformation in all species although the rate of biotranformation appeared to be species-dependent. Expand
Plasma Protein Binding of Deramciclane in Different Species
Deramciclane is a novel structure among anxiolytic agents. Pharmacokinetic studies in different species indicated the possibility of strong protein binding. The binding of deramciclane to plasma fromExpand
Absorption of the new anxiolytic compound deramciclane in rats, dogs and rabbits.
TLDR
The absorption of deramciclane fumarate, a new anxiolytic compound, was studied in rats, dogs and rabbits by using 3H-camphor- or 14C-phenyl-labelled radioisomers of the substance and the substance was readily absorbed from the intestinal tract after oral administration. Expand
Whole‐body Autoradiography and Quantitative Organ‐level Distribution Study of Deramciclane in Rats
The distribution of 3H‐labelled deramciclane (EGIS‐3886), a new 5‐HT2 antagonist with anxiolytic activity, has been investigated by whole‐body autoradiography and quantitative organ‐levelExpand
Deramciclane, a putative anxiolytic drug, is a serotonin 5-HT2C receptor inverse agonist but fails to induce 5-HT2C receptor down-regulation
TLDR
Data indicate that deramciclane is a 5- HT2C receptor inverse agonist and occupies 5-HT2C receptors during treatment, and that chronic treatment with deramCiclane does not lead to5-HT 2C receptor down-regulation. Expand
Absorption and pharmacokinetics of deramciclane in rat
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Fate of radiolabelled deramciclane (EGIS-3886) in rats, pharmacokinetics, excretion and separation of potential metabolites
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A high sensitive GC method for the determination of deramciclane and its N - desmethyl metabolite in rat and dog plasma
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Different antagonistic activity of deramciclane ( EGIS - 3886 ) on peripheral and central 5 - HT 2 receptors
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