Pharmacodynamics baseline effects

A mechanism-based PK/PD model for rHu-EPO was used to capture the physiological knowledge of the biological system. An open, two-compartment disposition model with parallel linear and nonlinear clearance, and endogenous EPO at baseline, was used to describe recombinant human erythropoietin (rHu-EPO) disposition after intravenous administration [35]. The pharmacodynamic effect of rHu-... 

The Phase I study was designed as a randomized, double-blind, placebo-controlled, single ascending dose study to evaluate the pharmacokinetics and pharmacodynamics of the new ERA. Cohorts of nine subjects with baseline hemoglobin levels less than 14.5 g/dl were randomized to receive ERA treatment (N= 6) or matched placebo (N= 3) at each dose level. The various dose levels considered in this study were lx, 3x, lOx, 30x, lOOx, and 300x. The objective of the study was to identify the pharmacological effective dose (PED), defined as the dose level where four or more treated subjects achieved more than 1 g/dl increase from baseline in hemoglobin within 28 days. 

The pharmacokinetics and pharmacodynamics of zaleplon (10 or 20 mg) and zolpidem (10 or 20 mg) have been investigated in a randomized, double-blind, crossover, placebo-controlled study in 10 healthy volunteers with no history of sleep disorder (15). The half-life of zaleplon was significantly shorter than that of zolpidem. Zaleplon produced less sedation than zolpidem at the two doses studied, and the sedation scores in the zaleplon groups returned to baseline sooner than in the zolpidem groups. Zaleplon had no effect on recent or remote recall, whereas zolpidem had a significant effect on both measures. 

At times, the effect measured during a pharmacodynamic study has a value before the drug is administered to the patient. In these cases, the drug changes the patient s baseline value. Examples of these types of measurements are heart rate and blood pressure. In addition, a given drug may increase or decrease the baseline value. Two basic techniques are used to incorporate baseline values into pharmacodynamic data. One way incorporates the baseline value into the pharmacodynamic model the other way transforms the effect data to take baseline values into account. 

Incorporation of the baseline value into the pharmacodynamic model involves the addition of a new term to the previous equations. Eq is the symbol used to denote the baseline value of the effect that will be measured. The form that these equations takes depends on whether the drug increases or decreases the pharmacodynamic effect. When the drug increases the baseline value, Eq is added to the equations ... 

If the drug decreases the baseline value, the drug effect is subtracted from Eq in the pharmacodynamic models ... 

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