Comparative therapeutic index, lethal time and safety margin of various toxicants and snake antivenoms using newly derived and old formulas

Abstract

Abstract Objective The assessment of clinical efficacy and toxicity is very important in pharmacology and toxicology. The effects of psychostimulants (e.g. amphetamine), psychotomimetics (e.g. Cannabis sativus) and snake antivenoms are sometimes unpredictable even at lower doses, leading to serious intoxication and fatal consequences. Hence, there is need to re-assess some formulas for calculation of therapeutic index, lethal time and safety margin with a view to identifying therapeutic agents with remarkable toxicity potentials. Results The therapeutic index formula $$\left[ {T_{1} = 3\left( {W_{a} \times 10^{ - 4} } \right)} \right]$$ T 1 = 3 W a × 10 - 4 was derived from T1 = LD50/ED50 and ED50 = $$\frac{{LD_{50} }}{3} x W_{a} \times 10^{ - 4}$$ L D 50 3 x W a × 10 - 4 . Findings have shown that, therapeutic index is a function of death reversal (s), safety factor (10−4) and weight of animal (Wa). However, the new safety margin formula $$\left[ {MS = \sqrt[3]{{\frac{{LT_{50} }}{{LD_{50} }}}} \times \frac{1}{{ED_{99} }}} \right]$$ M S = L T 50 L D 50 3 × 1 E D 99 derived from LT50 = $$\frac{{LD_{50} }}{{D_{1}^{p} }}$$ L D 50 D 1 p and MS = $$\frac{{LD_{1} }}{{ED_{99} }}$$ L D 1 E D 99 shows that safety margin is a function of cube root of ratio between LT50 and LD50 and ED100th. Concentration (k) of toxicant at the receptor $$\left[ {K = \sqrt[3]{{\frac{{LT_{50} }}{{LD_{50} }}}} \times \frac{1}{{T^{n} }}} \right]$$ K = L T 50 L D 50 3 × 1 T n derived from D1 × Tn = K and LD1 = $$\sqrt[3]{{\frac{{LT_{50} }}{{LD_{50} }}}}$$ L T 50 L D 50 3 shows that therapeutic index, lethal time and safety margin is a function of drug or toxicant concentration at the receptor, the drug-receptor interaction and dose of toxicant or drug administered at a particular time.

Keywords

• Therapeutic index
• Safety margin
• Efficacy
• Toxicity
• Weight
• Reversal