Median Effect Dose

Median Effective Dose (ED) The statistically derived single dose of a substance that can be expected to cause a defined nonlethal effect in 50% of a given population of organisms under a defined set of e.xperimental conditions. 

Therapeutic index. Ratio between the median lethal dose CLDso) and the median effective dose CED30) of a drug. 

The 5-fluorouracil (5-FU) and NONOate conjugates (Fig. 1.7) were prepared and their cytotoxicity was tested [90]. The median effect doses of the conjugates for DU145 and HeLa cancer cell lines were 2-4-fold lower than that of 5-FU. In another study by Wink et al, the cytotoxicity of cisplatin was enhanced about 60-fold after NONOate pretreatment for 30 min [91]. The enhancement of cytotoxicity of 5-FU/NONOate conjugates and cisplatin-NONOate combination has shown that there is a synergistic effect between anticancer drugs and NO. Another study by Jia et al. demonstrated that the cytotoxicity of Taxol was enhanced by S-nitrosocaptopril (Fig. 1.7) [92]. This effect is primarily mediated via the increased influx of Taxol by NO into intracellular compartments, while NO-induced cytotoxicity cannot be excluded. 

Piegorsh, W. (1989). Quantification of toxic response and the development of the median effective dose (ED50)—a historical perspective. Toxicol. Indust. Health. 5 55-62. 

Weil, C. (1952). Table for convenient calculation of median effective dose (LD50 or ED50) and instructions in their use. Biometrics 8 249-263. 

Potency is compared using the median effective concentration (EC50) or median effective dose (ED50), the meanings of which are subtly different. 

Hunt et al. [6] demonstrated that the DTI is also equivalent to the ratio of the therapeutic index (abbreviated to TI in Hunt et al. s paper in this chapter TI is defined differently, see Section 13.4.3) of the drug-carrier conjugate and that of the free drug. The therapeutic index (also called the therapeutic ratio) is a statistical measure defined as the ratio of the median toxic dose to the median effective dose [22]. 

Selected entries from Methods in Enzymology [vol, page(s)] Median effective dose, 235, 29, 31, 33 determination of median infectious dose, 235, 29-39 median lethal dose, 235, 29 moving average interpolation, 235, 32-34, 36-37, 39 probit analysis, 235, 31-36, 39 Reed-Muench method, 235, 30, 33-35 staircase method, 235, 33, 37-39 median response, 235, 29 dose range for animal experiments, 235, 29 50% end-point determination, 235, 29-30. 

The dose, symbolized by ED, producing a desired effect by a substance. The symbol is usually followed by a subscript number indicating the dose that has the desired effect on a certain percentage of the tested population. The median effective dose is ED50. 

In mice, the intravenous LD50 was greater than 25 mg/kg, and the MEDjq (median effective dose) was 0.1 mg/kg, for a safety margin greater than 250. In the dog, slight hypertension was seen at 0.1 and 1 mg/kg. In monkeys trained on a visual discrimination test, minimal behavioral effects were seen at 0.316 mg/kg, and moderate to marked effects at 1.0 mg/kg. 

In order to compare the safety and efficacy of drugs and their formulations, the therapeutic index, an estimate of therapeutic effects in relation to side effects, is often used (Figure 5.9B).The dose or concentration of a drug needed to ehcit a therapeutic effect in 50% of the population (median effective dose) is called the ED50. Typically a median lethal dose or LD50 is characterized for each drug in relevant experimental animals. The relationship of median lethal dose and effective dose comparison is the therapeutic index ... 

EDS0 The median effective dose (normally expressed as mg/kg or mg/g of body weight) producing a designated effect in 50 percent of the exposed test organism population. 

The quantal dose-effect curve is often characterized by stating the median effective dose (ED50), which is the dose at which 50% of individuals exhibit the specified quantal effect. (Note that the abbreviation ED50 has a different meaning in this context... 

Quantal Dose-Response Curves and the Median Effective Dose... 

FIGURE 1-4 Cumulative dose-response curve. The median effective dose CED5tl) is 10 mg, and the median toxic dose (TD50] is 320 mg. The therapeutic index (Tf) for this drug is 32. 

It should be noted, however, that the TI is a relative term. Acetaminophen, a nonprescription analgesic, has a TI of approximately 27 (i.e., the ratio of the median toxic dose to the median effective dose equals 27). Prescription agents tend to have lower TIs. For instance, the narcotic analgesic meperidine (Demerol)... 

Median effective dose (ABBR ED.o) The drug dose that produces a specific therapeutic response in 50 percent of the patients in whom it is tested. 

Therapeutic index (ABBR TI) A ratio used to represent the relative safety of a particular drug the larger the therapeutic index, the safer the drug. It is calculated as the median toxic dose divided by the median effective dose. (In animal trials, the median lethal dose is often substituted for the median toxic dose.)... 

FIGURE 1.11 a) The concept of antagonism or potentiation of pharmacologic effects, b) Drugs with higher therapeutic indices are safer. TI = therapeutic index, LD50 = median lethal dose, ED50 = median effective dose. 

ED50 is the median effective dose, a measure of response in the animal (other than death) the median effective dose is that at which 50% of the desired effect is achieved in 50% of the animals tested. Values for EDS0 are known and quoted for acute oral values. 

---