Review ArticlesQuantitative Determination of Drug Bioavailability and Biokinetic Behavior from Pharmacological Data for Ophthalmic and Oral Administrations of a Mydriatic Drug
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Challenging the dose-response-time data approach: Analysis of a complex system
2019, European Journal of Pharmaceutical SciencesCitation Excerpt :The premise of dose-response-time (DRT) data analysis is that the PD data provide sufficient information to identify a biophase-driven pharmacodynamic (PD) model (Smolen, 1971).
Dose-response-time modelling: Second-generation turnover model with integral feedback control
2016, European Journal of Pharmaceutical SciencesCitation Excerpt :This biophase library consists of feasible models derived from the kinetic information in the response-time course in combination with knowledge of the physiology. DRT data analysis dates back to the 1960s and 1970s when Smolen (Smolen and Weigand, 1973; Smolen, 1971; Smolen, 1976) and Levy (Levy, 1964) introduced the concept. Smolen used response data to quantify the bioavailability and biokinetic behaviour of a mydriatic drug after oral and ophthalmic administration whilst Levy derived a relation between the pharmacological effect and elimination rate of a mydriatic drug.
Dose-response-time data analysis involving nonlinear dynamics, feedback and delay
2014, European Journal of Pharmaceutical SciencesCitation Excerpt :The development of DRT has sometimes been held back by the belief that it suffered from several limitations. Thus, Smolen (cf. Smolen, 1971) thought that dose–response–time data analysis might be expected to fail unless linear kinetics, linear dynamics, time-constant parameters pertain, and no active metabolites, tolerance and rebound are involved. However, since then it has been demonstrated that the drug effect can be indirect, display nonlinear kinetics with regard to dose and time, exhibit hysteresis with the drug levels in the biophase and display feedback (cf. Gabrielsson et al., 2000).
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