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5 Principles of Clinical Pharmacology
Dan M. Roden

	Figure 5-1  The concept of a therapeutic ratio. Each panel illustrates the relationship between increasing dose and cumulative probability of a desired or adverse drug effect. Top. A drug with a wide therapeutic ratio, i.e., a wide separation of the two curves.
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	Figure 5-2  Idealized time-plasma concentration curves after a single dose of drug. A. The time course of drug concentration after an instantaneous IV bolus or an oral dose in the one-compartment model shown. The area under the time-concentration curve is clearly less with...
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	Figure 5-3  Mechanism of presystemic clearance. After drug enters the enterocyte, it can undergo metabolism, excretion into the intestinal lumen, or transport into the portal vein. Similarly, the hepatocyte may accomplish metabolism and biliary excretion prior to the entry of drug and metabolites to the systemic circulation.
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	Figure 5-4  Drug accumulation to steady state. In this simulation, drug was administered (arrows) at intervals = 50% of the elimination half-life. Steady state is achieved during initiation of therapy after ∼5 elimination half-lives, or 10 doses. A loading dose did not alter the eventual steady state achieved. A doubling of...
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	Figure 5-5  A. The efflux pump P-glycoprotein excludes drugs from the endothelium of capillaries in the brain, and so constitutes a key element of the blood-brain barrier. Thus, reduced P-glycoprotein function (e.g., due to drug interactions or genetically determined variability in gene transcription) increases...
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	Figure 5-6  A. CYP2D6 metabolic activity was assessed in 290 subjects by administration of a test dose of a probe substrate and measurement of urinary formation of the CYP2D6-generated metabolite. The heavy arrow indicates a clear antimode, separating poor metabolizer subjects (PMs, green), with two...
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