Pharmacokinetics of a F(ab′)2 scorpion antivenom administered intramuscularly in healthy human volunteers

This paper presents the first study of F(ab′)2 scorpion antivenom pharmacokinetics in humans after intramuscular (im) administration. The specific anti-Centruroides scorpion antivenom was used in 6 human healthy volunteers. The fabotherapeutic was administered as a 47.5 mg im bolus. Blood samples were drawn at 0, 5, 15, 30, 45, 60 , 90, 120, and 180 min, 6 h and at 1, 2, 3, 4, 10 and 21 days after antivenom administration. We measured antivenom concentrations in serum using a specific high sensitivity ELISA method for F(ab′)2. Antivenom concentration in serum was fit to a 3 compartment model (inoculation site, plasma and extra vascular extracellular space), it was assumed that the venom may also be irreversibly removed from plasma. Calculated time course of antivenom content shows that at any time no more that 16.6 (5.3, 31.9)% (median and 95% confidence interval) of the antivenom bolus is present in plasma. The time to peak plasma [F(ab′)2] was 45 (33, 74) h. The most significant antivenom pharmacokinetic parameters determined were: AUCim, ∞ = 803 (605, 1463) mg · h · L− 1; Vc = 8.8 (2.8, 23.6) L; Vss, im = 55 (47, 64) L; MRTim = 776(326, 1335) h; CLt = 3.7 (0.6, 1.9) mL · min− 1; fim, Vss = 0.300 (0.153, 0.466). Comparing these parameters with the ones obtained intravenously by Vázquez et al. [2], the parameters were more disperse between subjects, determined with more uncertainty in each individual subject, and the peak F(ab′)2 in plasma occurred with considerable delay; all indicating that the IM route should not be used to administer the antivenom, with the possible exceptionof cases occurring very far from hospitals, as an extreme means to provide some protection before the IV route becomes available.

Research Highlights
► Venoms act quickly and are composed of small molecules.
► Antivenoms are large and slowly absorbed after IM inoculation.
► Absorption of antivenoms after IM inoculation is quite variable is speed and extent.
► The IM route should not be used since is of low venom protective value.
► Quantitative evidence for the statements above is provided in the paper.