Population Pharmacokinetic-Pharmacodynamic Modelling of Angiotensin Receptor Blockade in Healthy Volunteers

@article{Csajka2002PopulationPM,
  title={Population Pharmacokinetic-Pharmacodynamic Modelling of Angiotensin Receptor Blockade in Healthy Volunteers},
  author={Chantal Csajka and Thierry Buclin and Karin E. Fattinger and Hans Rudolf Brunner and Jérôme Biollaz},
  journal={Clinical Pharmacokinetics},
  year={2002},
  volume={41},
  pages={137-152}
}
ObjectiveTo compare the pharmacokinetic and pharmacodynamic characteristics of angiotensin II receptor antagonists as a therapeutic class.DesignPopulation pharmacokinetic-pharmacodynamic modelling study.MethodsThe data of 14 phase I studies with 10 different drugs were analysed. A common population pharmacokinetic model (two compartments, mixed zero- and first-order absorption, two metabolite compartments) was applied to the 2685 drug and 900 metabolite concentration measurements. A standard… 

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References

SHOWING 1-10 OF 46 REFERENCES

Pharmacokinetic-Pharmacodynamic Profile of Angiotensin II Receptor Antagonists

The characterisation of the pharmacokinetic-pharmacodynamic relationships of nonpeptide angiotensin antagonists in humans deserves further refinement for designing optimal therapeutic regimens and proposing dosage adaptations in specific conditions.

Concentration-Effect Analysis of Antihypertensive Drug Response

This mode of analysis warrants early inclusion in the clinical development of any new antihypertensive agent, so that the familiar difficulties in identifying the optimum dosage range are avoided.

Evaluation of the angiotensin challenge methodology for assessing the pharmacodynamic profile of antihypertensive drugs acting on the renin-angiotensin system.

This experimental method represents a valid surrogate for the therapeutic target and a useful tool for the pharmacokinetic and pharmacodynamic profiling of drugs acting on the renin-angiotensin system.

Drug concentration response relationships in normal volunteers after oral administration of losartan, an angiotensin II receptor antagonist

It is concluded that losartan produces a dose‐dependent, effective angiotensin II blockade that is largely determined by the active metabolite EXP3174.

Simultaneous Modeling of Pharmacokinetics and Pharmacodynamics with a Nonparametric Pharmacodynamic Model

The results suggest that the method can faithfully estimate the Ce‐E curve for a variety of PD models and degrees of experimental error when its basic assumption of time‐invariant PD holds.

SC-52458, an orally active angiotensin II-receptor antagonist: inhibition of blood pressure response to angiotensin II challenges and pharmacokinetics in normal volunteers.

The novel AT1-receptor antagonist SC-52458 is well tolerated and orally active, and produces a rapid-onset inhibition of the renin-angiotensin system and reduces BP response to Ang II for > or = 10 h, which promise strong antihypertensive properties.

Clinical and hormonal effects of the new angiotensin II receptor antagonist LRB081.

Maximal BP-blocking effect and maximal plasma drug level coincided, suggesting that the unmetabolized LRB081 is responsible for the antagonistic effect.

Concentration-effect analysis of antihypertensive drug responses.

The findings suggest that the definition of individual concentration-effect relations may be of value in the rational choice of antihypertensive drug therapy and optimization of dose and dose frequency.

Oral Administration of DuP 753, a Specific Angiotensin II Receptor Antagonist, to Normal Male Volunteers: Inhibition of Pressor Response to Exogenous Angiotensin I and II

DuP 753 appears to be a well-tolerated, orally active, potent, and long-lasting antagonist of angiotensin II in men.

Dose-response relationships following oral administration of DuP 753 to normal humans.

DuP 753 appears to be a well tolerated, orally active, potent and long-lasting antagonist of angiotensin II in humans.