https://nova.newcastle.edu.au/vital/access/ /manager/Index en-au 5 Population pharmacokinetics of an Indian F(ab')₂ snake antivenom in patients with Russell's viper (<i>Daboia russelii</i>) bites https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21161 Daboia russelii) envenoming in Sri Lanka. All patients received Indian F(ab’)₂ snake antivenom manufactured by VINS Bioproducts Ltd. Antivenom concentrations were measured with sandwich enzyme immunoassays. Timed antivenom concentrations were analysed using MONOLIXvs4.2. One, two and three compartment models with zero order input and first order elimination kinetics were assessed. Models were parameterized with clearance(CL), intercompartmental clearance(Q), central compartment volume(V) and peripheral compartment volume(VP). Between-subject-variability (BSV) on relative bioavailability (F) was included to account for dose variations. Covariates effects (age, sex, weight, antivenom batch, pre-antivenom concentrations) were explored by visual inspection and in model building. There were 75 patients, median age 57 years (40-70y) and 64 (85%) were male. 411 antivenom concentration data points were analysed. A two compartment model with zero order input, linear elimination kinetics and a combined error model best described the data. Inclusion of BSV on F and weight as a covariate on V improved the model. Inclusion of pre-antivenom concentrations or different batches on BSV of F did not. Final model parameter estimates were CL,0.078 Lh⁻¹, V,2.2L, Q,0.178Lh⁻¹ and VP,8.33L. The median half-life of distribution was 4.6h (10-90%iles:2.6-7.1h) and half-life of elimination, 140h (10th-90th percentilesx:95-223h). Conclusion: Indian F(ab’)₂ snake antivenom displayed biexponential disposition pharmacokinetics, with a rapid distribution half-life and more prolonged elimination half-life.]]> Wed 11 Apr 2018 16:20:31 AEST ]]> Detection of snake venom in post-antivenom samples by dissociation treatment followed by enzyme immunoassay https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29575 Wed 11 Apr 2018 15:46:56 AEST ]]> Detection of venom–antivenom (VAV) immunocomplexes in vitro as a measure of antivenom efficacy https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14537 Wed 11 Apr 2018 14:02:42 AEST ]]> Detection of venom after antivenom administration is largely due to bound venom https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27073 4) serum samples were available from 255 Russell's viper (Daboia russelii) envenomed patients. Enzyme-linked immunosorbent assay was used to measure venom, antivenom and venom-antivenom (VAV) complexes. In 79/255 (31%) there was persistent/recurrent venom detected despite antivenom being present. In these post-antivenom samples, VAV was also detected at the same time as venom was detected. Anti-horse (aH) antiserum was bound to UltraLink (UL) resin and added to in vitro venom-antivenom mixtures, and 15 pre- and post-antivenom samples from patients. There was significantly less free venom detected in in vitro venom-antivenom mixtures to which ULaH had been added compared to those without ULaH added. In 9 post-antivenom patient samples the addition of ULaH reduced venom detected by a median of 80% (69%-88%) compared to only 20% in four pre-antivenom samples. This suggests that the detection of persistent/recurrent venom post-antivenom is due to bound and not free venom.]]> Sat 24 Mar 2018 07:25:20 AEDT ]]>