Influence of Prognostic Factors

One of the aims of modeling is to identify influential prognostic factors such as body weight, age, gender, food, smoking habits, etc., on the fundamental PK/PD parameters. Nisoldipine is formulated as a once-a-day controlled release formulation of a dihydropyridine calcium channel antagonist which is approved in the United States for the treatment of hypertension. Food was found to increase the maximum concentration (Cmax: 2.75 vs. 7.5 pg/L) and decrease the extent of bioavailability (AUC: 70.4 vs. 53 pg.hr/L) of the controlled release product. The influence of the higher concentrations on the decrease of blood pressure was evaluated using a previously developed concentration-effect (blood pressure) model [14]. Simulations of the effect under the Fed condition allowed in alleviating the safety concern of a large drop in blood pressure. However in the labeling of Sular, administration on an empty stomach for optimal bioavailability was recommended. The docetaxel PK/PD relationship, in patients with cancer, was successful in identifying a subpopulation, patients with liver impairment, to be more prone to neutropenia (grade 4) [15]. This important finding was the basis for the dosing recommendations in the labeling, for patients with liver insufficiency. The drug development program of docetaxel exemplifies the value added by the incorporation of prospective planning on the use of M&S into the clinical trials.

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Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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