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** Pharmacokinetic-pharmacodynamic PK-PD) modeling **

Population PK/PD models, which in addition to the characterization of PK and PD, involve relationships between covariates (for instance, patient characteristics such as age, body weight) and PK/PD parameters, allow us to assess and to quantify potential sources of variability in exposure and response in specific target population, even under erratic and limited sampling conditions. Often implications of significant covariate effects can be evaluated by computer simulations using the population PK/PD model. [Pg.371]

PK models (Section 13.2.4), PD models (Section 13.2.5), and PK/PD models (Section 13.2.6) can be used in two different ways, that is, in simulations (Section 13.2.7) and in data analysis (Section 13.2.8). Simulations can be performed if the model structure and its underlying parameter values are known. In fact, for any arbitrary dose or dosing schedule the drug concentration profile in each part of the model can be calculated. The quantitative measures of the effectiveness of drug targeting (Section 13.4) can also be evaluated. If actual measurements have been performed in in-vivo experiments in laboratory animals or man, the relevant model structure and its parameter values can be assessed by analysis of plasma disappearance curves, excretion rate profiles, tissue concentration data, and so forth (Section 13.2.8). [Pg.338]

Lorazepam The PK-PD modeling of the psychomotor and mnesic effects of a single 2 mg oral dose of lorazepam in healthy volunteers showed that the parameter values derived from PK/PD modeling, and especially the EC values, may provide sensitive indices that can be used, rather than the raw data derived from PD measurements, to compare CNS effects of benzodiazepines [Pg.370]

Cetrizine The PK-PD modeling characterized the time course of cetirizine effect on histamine-induced skin reactions (wheal and flare). The histamine-induced flare was at least 80% inhibited at the start of the second administration. Thereafter, on successive administrations, the inhibition was even more pronounced and the response control was nearly total [Pg.370]

In the process of PK/PD modeling, it is important to describe, prospectively, the objectives of the modeling, the study design, and the available PK and PD data. The assumptions of the model can be related to dose-response, PK, PD, or one or more of the assumptions listed in Table 18.1. [Pg.347]

Luckow, V. and Della Paschoa, O., PK/PD modeling of high-dose diltiazem—absorption-rate dependency of the hysteresis loop, Int.. Clin. Pharmacol. Ther., 35, 418-425,1997. [Pg.376]

Evaluation of Effectiveness of Drug Targeting Using PK and PK/PD Modelling [Pg.359]

FormoteroF Interactions of formoterol and theophylline were evaluated with the use of PK/PD modeling. The values for the eosinopenic effects were fixed at 0. Effects of both drugs combined were described with a noncompetitive interaction model [Pg.370]

Piperacillin- tazobactam In vitro anti-infective effect of piperacillin-tazobactam (PIP-TZB) combinations on Escherichia coli showed through a PK/PD model that for these combinations, three-times-a-day administration is as effective as four times a day. Pharmacodynamic activity of the combinations can be prolonged by sufficiently high inhibitor concentrations [Pg.370]

One should definitely examine them to appreciate how easy it has become to create and analyze PK and PD models. If you are interested in further information, a literature search on of electronic databases for material on PK/PD modeling should use both the spellings "modeling" and "modelling" because they are used interchangeably. [Pg.360]

** Pharmacokinetic-pharmacodynamic PK-PD) modeling **

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