Drug concentration minimum toxic

Fig. 1. Blood—drug concentration curve used to determine bioavailabiLitv and bioequivalence. C is the maximum dmg concentration in the blood and corresponds to some The AUC (shaded) represents the total amount of orally adininistered dmg the time from points A to B represents dmg onset, from points B to D, the duration MEC = minimum effective concentration MTC = minimum toxic concentration and TI = therapeutic index.

Figure 12.1 shows the plasma concentration versus time profile of an orally administered hypothetical drug. When the drug concentration in plasma equals the minimum effective concentration (MEC), therapeutic response is initiated. When the concentration exceeds the minimum toxic concentration (MTC), the drag causes toxic responses. Therefore, for ideal therapeutic response, the plasma concentration of drugs should be between the MEC and MTC. This region is called the therapeutic window. In Figure 12.1 the MEC is 1.5 ng/ mL, and the MTC is 3.5 ng/mL. The therapeutic window is between 1.5 and 3.5 ng/mL. 

Now for maintaining the serum concentration above the MEC for longer duration, the second dose of drug should be given about 7 to 8 hours after the first dose, otherwise when it is given after 7 to 8 hours it will take extra time to reach the MEC or if it is given prior to 7 to 8 hours the second dose in combination with the first dose effect crosses the minimum toxic concentration (MTC). 

Narrow Therapeutic Index Drugs Drugs having, for example, less than a two-fold difference in the minimum toxic concentrations and the minimum effective concentrations (21 CFR 320.33 (c)). 

Similarly, the peaks between doses should not exceed toxic levels. Together, the minimum effective concentration and toxic level define the therapeutic window of the drug. 

Drug Minimum Effective Concentration (MEC) (flg/mL) Minimum Toxic Concentration (MTC) (iiglmL) Average Half-Life (hr) Average Oral Bioavailability (%) Average Protein Binding (%) Important Metabolizing Enzymes... 

Drug Mininriunri Toxic Concentration at 24 hrs After (pmol/L) Minimum Toxic Concentration at 48 hrs After Dose (fUnol/L) Minimum Toxic Concentration at 72 hrs After Dose (p,mol/L) Average Half-Life at 100 Xmol/L (hr) Average Half-Life at lOfxmol/L (hr) Average Half-Life at 1 pmol/L (hr)... 

When a plasma-concentration curve is constructed for different patients that have been given an identical dose of an identical drug, interindividual differences will be noted. In some cases, plasma concentrations in one patient may remain below the minimal effective concentration, whereas the plasma concentration in another patient reaches the minimum toxic concentration. Besides some very obvious causes, such as body weight and body composition, some other factors involved in the interindividual variability in pharmacokinetics are concisely described below. 

Figure 3-6. The therapeutic window for theophylline in a 13-year-old patient. The minimum effective concentration in this patient was found to be 8 mg/L the minimum toxic concentration was found to be 16 mg/L. The therapeutic window is indicated by the colored area. In order to maintain the plasma concentration Cp within the window, the drug must be given at least once every half-life (7 5 hours in this patient), since the minimum effective concentration is half the minimum toxic concentration and Cp will decay by 50% in one half-life. (Note This concept applies to drugs given in the ordinary, prompt-release form. Slow-release formulations can often be given at longer intervals.)...

A 60-year-old man enters the hospital with a myocardial infarction and a severe ventricular ar-rh)Thmia. The antiarrhythmic drug chosen has a narrow therapeutic window the minimum toxic plasma concentration is 1.5 times the minimum therapeutic plasma concentration. The half-life is 6 hours. It is essential to maintain the plasma concenti ation above the minimum therapeutic level to prevent a possibly lethal airhythmia. Of the following, the most appropriate dosing regimen would be... 

Figure 1.1 Atypical plot (rectilinear paper) of plasma concentration versus time following the administration of a drug by an extravascular route. MTC, minimum toxic concentration MEC, minimum effective concentration.

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