Determination of the half effective amount (ED50) of sodium pentobarbital (57-33-0)

Pharmacological experiment report

Experiment: Determination of half effective amount (ED 50 ) of pentobarbital sodium

First, the purpose and principle of the experiment

The ED 50 value of hypnotic effect of intraperitoneal injection of pentobarbital sodium on mice was determined. Sodium pentobarbital is a barbiturate sedative-hypnotic drug. The hypnotic effect produced by intraperitoneal injection of mice at an appropriate dose is usually judged by the disappearance of righting reflex. The indicator is only positive (sleep) and negative (not sleeping). Both phenomena are qualitative reactions. The abscissa of the mass response dose-effect curve is the logarithmic dose, and when the ordinate uses the frequency of the positive reaction, it is generally the normal distribution curve. If the cumulative positive frequency is used as the ordinate, a standard S-shaped curve can be obtained. The central portion of the curve (50% of the reaction) is close to a straight line with the largest slope, and the corresponding dose is the dose that causes an effect on half of the individuals in the population, commonly referred to as the half effect amount. If the effect is efficacy, the half effective amount (ED 50 ) is called; if the effect is death, the median lethal dose (LD 50 ) is called. These values ​​are important parameters for evaluating the strength of drug action and drug safety. 021-51602548

The design conditions of Sun's improved Kaerber method are as follows: the number of experimental animals in each group is equal, and the doses in each group are in a similar ratio. The response rate of each group of animals is roughly consistent with the normal distribution. If Xm is the logarithm of the maximum response rate group dose, i is the logarithm of the dose ratio between groups, p is the reaction rate of each group, Pm is the highest reaction rate, Pn is the lowest reaction rate, and n is the number of experimental groups, then:

ED 50 = lg -1 [Xm-i(∑P-0.5)+i/4(1-Pm-Pn)]

When containing 0% and 100% reaction rate,

ED 50 = lg -1 [Xm-i(∑P-0.5)]

95% confidence limit for ED 50 = lg -1 (lgED 50 ± 1.96·S)

Where S=i

Second, the experimental materials

50 mice, 1% sodium pentobarbital solution mouse cage, balance, 0.5 ml or 0.25 ml syringe.

Third, the experimental steps 021-51602548

1. Determine the dose to be administered: First, a small amount of animals should be pre-tested to obtain a minimum dose (ED 100 ) of 100% hypnotic reaction rate of pentobarbital sodium and a maximum dose of 0% (ED 0). ). Then, within this dose range, it is divided into several dose groups (generally 4-8 groups) according to the equal ratio series. The common ratio (r) of each group dose is r= n-1 √ED 100 /ED 0

After r is obtained, multiplying r from the first dose group (ED 0 ) yields the dose of the next adjacent group. If divided into 5 groups, the doses of each group are ED 0 , r·ED 0 , r 2 · ED 0 , r 3 · ED 0 , r 4 · ED 0 , r 5 · ED 0 .

2. Administration: 50 healthy mice weighing about 25 g were randomly selected and randomly divided into 5 groups, 8 in each group (excluding 2 mice with extreme weight). The concentration of each group listed in Table 1 was intraperitoneally injected with 0.1 ml/10 g.

3. Recording results: The disappearance of the righting reflex was taken as the index of falling into sleep, and the hypnotic effect of the drug was observed. The number of sleeping rats within 15 minutes after intraperitoneal injection in each group was recorded and filled in Table 1.

IV. Experimental Results Shanghai Yubai Biotechnology Co., Ltd. 021-51602548

Table 1 Table for calculating pentabarbital sodium ED 50

Group

Number of mice

Drug concentration

(mg/ml)

Dosage

(mg/kg)

Logarithmic dose

Hypnotic rats

P

P 2

1

8

2.0

20

1.3010

0

0

0

2

8

2.6

26

1.4150

3

0.375

0.141

3

8

3.5

35

1.5441

4

0.500

0.250

4

8

4.6

46

1.6628

6

0.750

0.563

5

8

6.0

60

1.7781

8

1

1

According to the data in Table 1 and the above formula, ED 50 = 31.90 can be obtained.

Precautions

1. To reduce the error, dispense by 1 person

2, keep the environment quiet

3. If there is a positive animal in the first group, increase the low dose group down by the public ratio (d0=d1/r)

4. The last group of animals are not all positive, and one dose is added upwards (dk+1=dkr)

Shanghai Yubai Biotechnology Co., Ltd. 021-51602548

Finished Dosage Formulation

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