Evaluation of interethnic differences in repinotan pharmacokinetics by using population approach.

@article{Tanigawa2006EvaluationOI,
  title={Evaluation of interethnic differences in repinotan pharmacokinetics by using population approach.},
  author={Takahiko Tanigawa and Roland Heinig and Yoshihiro Kuroki and Shun Higuchi},
  journal={Drug metabolism and pharmacokinetics},
  year={2006},
  volume={21 1},
  pages={
          61-9
        }
}
Repinotan is a selective full serotonin receptor agonist at the 5-HT1A subtype which has been studied in phase I and II studies involving over 500 healthy subjects and patients. Repinotan is primarily metabolized by CYP2D6 which is known to be subject to polymorphism and ethnic differences in its quantitative and qualitative expression pattern. In order to investigate the effect of ethnicity on repinotan pharmacokinetics (PK) between a Caucasian and Japanese population and to explain PK… 
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The mRECT demonstrated the feasibility of conducting a rigorous trial using a short therapeutic window demanding clinical and radiographic criteria to optimize patient selection and a Point-of-Care test to achieve a targeted exposure to repinotan.
A Randomized , Double-Blind , Placebo-Controlled Trial to Evaluate the Efficacy , Safety , Tolerability , and Pharmacokinetic / Pharmacodynamic Effects of a Targeted Exposure of Intravenous Repinotan in Patients With Acute Ischemic Stroke Modified
Background and Purpose—Repinotan hydrochloride is a serotonin (5-HT)1A receptor full agonist with evidence of neuroprotection in animal models of permanent and transient focal ischemia. The purpose
"A randomized, double-blind, placebo-controlled trial to evaluate the efficacy, safety, tolerability, and pharmacokinetic/ pharmacodynamic effects of a targeted exposure of intravenous repinotan in patients with acute ischemic stroke"
mRECT demonstrated the feasibility of conducting a rigorous trial using a short therapeutic window demanding clinical and radiographic criteria to optimize patient selection and a Point-of-Care test
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References

SHOWING 1-10 OF 24 REFERENCES
Molecular basis of genetic variation in debrisoquin hydroxylation in Chinese subjects: Polymorphism in RFLP and DNA sequence of CYP2D6
TLDR
The C/T188,G/A1934, G/C4268, and RFLP polymorphisms may explain the interracial variations between Chinese and white subjects, as well as the genetic variations among Chinese subjects.
Polymorphic Drug Oxidation
TLDR
The high incidence of PM (and of heterozygous extensive metabolisers) of S-mephenytoin in Asia might be the reason for the reported higher sensitivity of Orientals to diazepam compared with Caucasians.
Population PKPD modelling of the long-term hypoglycaemic effect of gliclazide given as a once-a-day modified release (MR) formulation.
TLDR
This population PKPD analysis has characterized the relationship between the exposure to gliclazide and its long-term hypoglycaemic effect, and has established that the intersubject variability in response is mostly related to disease state.
Repinotan (BAY × 3702): A 5HT1A Agonist in Traumatically Brain Injured Patients
TLDR
Repinotan treatment had no apparent adverse effects on intracranial pressure, hemodynamic parameters or laboratory parameters and serious adverse events were considered related to drug treatment, with the possible exception of one case of inappropriate ADH secretion.
Population Pharmacokinetics of Perhexiline From Very Sparse, Routine Monitoring Data
TLDR
The results confirm and extend the existing pharmacokinetic data on perhexiline, especially the bimodal distribution of CL/F manifested via an inherited deficiency in hepatic and extrahepatic CYP2D6 activity.
Evidence for a new variant CYP2D6 allele CYP2D6J in a Japanese population associated with lower in vivo rates of sparteine metabolism.
TLDR
Data suggest that CYP2D6J encodes an enzyme having lower rates of sparteine metabolism.
Population Pharmacokinetics of Ceftizoxime Administered by Continuous Infusion in Clinically Ill Adult Patients
TLDR
Two models for ceftizoxime clearance, mixture and nonmixture, were found and are presented and work is needed to validate the model for drug clearance and to evaluate its predictive performance.
The BRAINS Study: Safety, Tolerability, and Dose-finding of Repinotan in Acute Stroke
  • P. Teal, F. Silver, D. Simard
  • Medicine
    Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques
  • 2005
TLDR
The incidence of adverse events was comparable with all doses of repinotan and placebo, and no safety issues were observed, and a trend toward better tolerability with evidence of efficacy was observed with the rep inotan 1.25 mg/d dose.
Evaluation of Mixture Modeling with Count Data Using NONMEM
TLDR
A simulation study was undertaken to evaluate mixture modeling with NONMEM and explore the following questions: what is the probability of concluding that a mixed population exists when there truly is not a mixture, and how well can the mixture be estimated, both in terms of the population parameters and the individual subject classification.
Simulation for Population Pharmacodynamic Analysis of Dose-Ranging Trials: Usefulness of the Mixture Model Analysis for Detecting Nonresponders
TLDR
Different data analysis methods and trial designs are evaluated to estimate the population pharmacodynamic parameters from the dose-ranging trials, which include NRs, and it is determined that a new analysis method that discriminates between responders (RPs) and NRs is necessary for the estimation of the doses-response relationships.
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