FIELD: medicine.
SUBSTANCE: invention relates to medicine, namely, to pharmacology and toxicology, and can be used to determine the personalised effective dose of cholinesterase inhibitors for the body at the preclinical level. The experimental animals are pre-divided into functional groups according to the value of the dibucaine number for butyryl cholinesterase: above 75%, 35 to 75%, below 35%. The dibucaine number is calculated by the formula
wherein DN is the value of the dibucaine number, %; Einhib. is the value of activity of dibucaine-inhibited butyryl cholinesterase, E·l-1; Etotal is the value of activity of butyryl cholinesterase, E·l-1. The studied cholinesterase inhibitor is then administered to the experimental animals in accordance with the determined functional group starting with the average dose Danimal according to Table 3 of the descriptions, until the target effect is achieved in the experimental animal: suppression of acetylcholinesterase from 20 to 30%, the criterion whereof is determined by colorimetry. The experimental data are then extrapolated as applied to humans, calculating the effective dose of the studied cholinesterase inhibitor as applied to humans by the formula
wherein Dhuman is the predicted numerical value of the dose of the desired probability of the target effect for humans, mg/kg; Danimal is the determined numerical value of the dose of the desired probability of the target effect for an experimental animal, mg/kg; Mhuman/animal is the average human/animal body weight, kg.
EFFECT: possibility of increasing the objectivity and accuracy of interpretation of experimental data, as well as reduction in labour costs in planning of clinical trials of anti-cholinesterase products, due to the objective assessment of the effectiveness and toxicity of the studied cholinesterase inhibitors accounting for the functional differences in the butyryl cholinesterase activity at the preclinical level using the determined algorithm of actions.
1 cl, 4 tbl
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RU2550080C1 |
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RU2704264C1 |
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RU2754133C1 |
OXALATE N,N-DIMETHYL-2-N,N-DIMETHYLAMINOMETHYLPYRIDYL-3-CARBAMATE, POSSESSING ANTI-CHOLINESTERASE ACTIVITY AND ABILITY TO IMPROVE COGNITIVE FUNCTIONS | 2007 |
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Authors
Dates
2022-06-21—Published
2021-06-15—Filed