Drug concentration minimum effective

Digoxin has a narrow therapeutic window, and its dosing must be carefully managed. The drug s minimum effective concentration is about 1 ng/mL. About 60% is excreted in the urine the rest is metabolized in the liver. The normal clearance of digoxin is 7 L/h/70 kg volume of distribution is 500 L/70 kg and bioavailability is 70%. If your 70-kg patient s renal function is only 30% of normal, what should be the daily oral maintenance dosage in order to achieve a safe plasma concentration of 1 ng/mL The Skill Keeper Answer appears at the end of the chapter. 

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. 

If the minimum effective concentration is 3 mg/mL, what is the onset, intensity, and duration of action of the administered drug for which the following plasma concentration versus time data is available ... 

More recent investigations on the antimycobacterial activity of pamamycin-607 (lb) on 25 independent M. tuberculosis clinical isolates (either susceptible, mono-, or multiresistant to the first line antituberculous drugs) established minimum inhibitory concentrations MICjoo in the range of 1.5-2.0 pg/ml, while the MICjoo of lb for a bioluminescent laboratory strain of M. tuberculosis (H37Rv) was determined as 0.55 pg/ml [3a]. Parallel studies on the effect of lb on the cell cycle distribution of human (HL-60) cells by flow cytometry indicated no... 

Fig. 1.4. 5 Shows the administration of 2nd dose between the 7-8 hours interval which maintains the drug plasma levels above minimum effective concentration.

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. 

PROBLEM An oral drug has a dose of 500 mg, oral bioavailability of 80%, Vd of 70 L, kel of 0.3 h 1, and fcab of 0.8 IT1. The drug has been prescribed to be taken every 4 hours. If the minimum effective concentration of the drug is 1.5 /xg / ml., will the patient still have an effective concentration of the drug when the second dose is administered ... 

The function r (E) can take various forms describing the natural growth of the cell population in the absence of drug [372,445], while g (c) can be either linear or nonlinear [435,446,447]. Due to the competitive character of the functions r (E) and g (c), the cell number vs. time plots are usually biphasic with the minimum effective concentration of drug being the major determinant for the killing or regrowth phases of the plot. 

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