Antivenoms: potency or median effective dose, which to use?

Abstract

Dear Editor:In the field of envenomations by poisonous animals, the ability of antivenoms to neutralize the lethal effects of venoms is estimated by a biological assay in which mice are inoculated with a range of venom/antivenom concentrations and the survival/death ratio is recorded. A statistical technique (e.g., Probit) is employed to estimate the amount of antivenom that protects 50% of the animals. This quantity is called median effective dose or effective dose 50 (ED 50 ) and is normally expressed in volume units (i.e., mL or μL). The ED 50 is used in an expression for the assessment of the potency (P) of the antivenom, as follows (1, 2): P = (n -1)LD 50 / ED 50 [1]where "LD 50 " is the median lethal dose (mass of venom that kills 50% of mice), and "n" is the number of LD 50 s used in the assay. "P" is the amount of venom, expressed in mass units or number of median lethal doses, that is completely neutralized per unit volume of antivenom (the expression "(n -1) LD 50 " is used instead of the total amount of venom, nLD 50 , because at the endpoint of the neutralization assay, one LD 50 remains unneutralized and causes the death of 50% of mice). However, in the literature, it is very frequent to find that the same term, ED 50 , is utilized to represent

Venomics of the beaked sea snake, Hydrophis schistosus: A minimalist toxin arsenal and its cross-neutralization by heterologous antivenoms

“…The efficacy of antivenom was expressed as median effective dose (ED 50 , the amount of reconstituted antivenom in µL that gives 50% survival of the animals tested), effective dose ratio (ER 50 , the amount of toxin neutralized per mL antivenom where 50% of envenomed mice survived), as well as "potency" (P, the amount of toxin (in mg) that is completely neutralized per mL of antivenom), calculated as described by Morais et al [42] and Leong et al. [43].…”

“…The minimization of molecular diversity of the toxin arsenal of Hydrophis schistosus however has not compromised its extremely potent toxicity. [42]. Parentheses indicate the 95% CI.…”

“…NKMAV: Thai Naja kaouthia monovalent antivenom; NPAV: Thai Neuro polyvalent antivenom. ED 50 : median effective dose, defined as the volume of reconstituted antivenom that protects 50% of mice from death; ER 50 : Effective dose ratio, defined as amount of venom toxin neutralized per mL antivenom where 50% of envenomed mice survived; P: Potency, defined as amount of venom toxin neutralized per mL antivenom in total (presumably 100% survival conferred) [42]. Parentheses indicate the 95% CI.…”

Venom and Purified Toxins of the Spectacled Cobra (Naja naja) from Pakistan: Insights into Toxicity and Antivenom Neutralization

“…Neutralization capacity was also expressed in term of "neutralization potency" (P, the amount of venom that is completely neutralized by a unit volume of antivenom) calculated according to Morais and others. 26 The neutralization potency is a more direct indicator of antivenom neutralizing capacity and is theoretically unaffected by the number of LD 50 in the challenge dose.…”

Revisiting Notechis scutatus venom: on shotgun proteomics and neutralization by the “bivalent” Sea Snake Antivenom

“…Neutralizing capacity was expressed as ED 50 , defined as the amount of antivenom that confers 50% survival in the venom-challenged animals. Neutralization capacity was also expressed in term of 'neutralization potency' (P, the amount of venom that is completely neutralized by a unit volume of antivenom) calculated according to Morais et al [22]. The neutralization potency is a more direct indicator of antivenom neutralizing capacity, and is theoretically unaffected by the number of LD 50 in the challenge dose.…”