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Population Pharmacokinetics of an Indian F(ab')2 Snake Antivenom in Patients with Russell's Viper (Daboia russelii) Bites.

Isbister GK, Maduwage K, Saiao A, Buckley NA, Jayamanne SF, Seyed S, Mohamed F, Chathuranga U, Mendes A, Abeysinghe C, Karunathilake H, Gawarammana I, Lalloo DG, de Silva HJ - PLoS Negl Trop Dis (2015)

Bottom Line: 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.Indian F(ab')2 snake antivenom displayed biexponential disposition pharmacokinetics, with a rapid distribution half-life and more prolonged elimination half-life.

View Article: PubMed Central - PubMed

Affiliation: Clinical Toxicology Research Group, University of Newcastle, Newcastle, New South Wales, Australia; South Asian Clinical Toxicology Research Collaboration (SACTRC), Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka.

ABSTRACT

Background: There is limited information on antivenom pharmacokinetics. This study aimed to investigate the pharmacokinetics of an Indian snake antivenom in humans with Russell's viper bites.

Methods/principal findings: Patient data and serial blood samples were collected from patients with Russell's viper (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 (40-70 y) 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 L h(-1), V,2.2L, Q,0.178 L h(-1) and VP,8.33L. The median half-life of distribution was 4.6 h (10-90%iles:2.6-7.1 h) and half-life of elimination, 140 h (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.

No MeSH data available.


Related in: MedlinePlus

Plots of antivenom concentration versus time for 1000 patients simulated from the final model individual predicted patient parameters for 10 vials of antivenom given over 20min, 1h and 2h, comparing the median concentrations for all three regimens (A), and the median and 10% and 90% percentile concentrations for a 20 minute infusion (B), 1 hour infusion (C) and 2 hour infusion (D).
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pntd.0003873.g002: Plots of antivenom concentration versus time for 1000 patients simulated from the final model individual predicted patient parameters for 10 vials of antivenom given over 20min, 1h and 2h, comparing the median concentrations for all three regimens (A), and the median and 10% and 90% percentile concentrations for a 20 minute infusion (B), 1 hour infusion (C) and 2 hour infusion (D).

Mentions: Simulations for one dose (10 vials) of antivenom given over 20 minutes, 1 hour and 2 hours shows there is a slightly lower and later peak antivenom concentration with slower infusions (Fig 2). Simulations for two doses of antivenom shows that antivenom concentrations decrease rapidly after each dose and there are low but persistent levels of antivenom after one dose and both two doses regimens (Fig 3).


Population Pharmacokinetics of an Indian F(ab')2 Snake Antivenom in Patients with Russell's Viper (Daboia russelii) Bites.

Isbister GK, Maduwage K, Saiao A, Buckley NA, Jayamanne SF, Seyed S, Mohamed F, Chathuranga U, Mendes A, Abeysinghe C, Karunathilake H, Gawarammana I, Lalloo DG, de Silva HJ - PLoS Negl Trop Dis (2015)

Plots of antivenom concentration versus time for 1000 patients simulated from the final model individual predicted patient parameters for 10 vials of antivenom given over 20min, 1h and 2h, comparing the median concentrations for all three regimens (A), and the median and 10% and 90% percentile concentrations for a 20 minute infusion (B), 1 hour infusion (C) and 2 hour infusion (D).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4489840&req=5

pntd.0003873.g002: Plots of antivenom concentration versus time for 1000 patients simulated from the final model individual predicted patient parameters for 10 vials of antivenom given over 20min, 1h and 2h, comparing the median concentrations for all three regimens (A), and the median and 10% and 90% percentile concentrations for a 20 minute infusion (B), 1 hour infusion (C) and 2 hour infusion (D).
Mentions: Simulations for one dose (10 vials) of antivenom given over 20 minutes, 1 hour and 2 hours shows there is a slightly lower and later peak antivenom concentration with slower infusions (Fig 2). Simulations for two doses of antivenom shows that antivenom concentrations decrease rapidly after each dose and there are low but persistent levels of antivenom after one dose and both two doses regimens (Fig 3).

Bottom Line: 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.Indian F(ab')2 snake antivenom displayed biexponential disposition pharmacokinetics, with a rapid distribution half-life and more prolonged elimination half-life.

View Article: PubMed Central - PubMed

Affiliation: Clinical Toxicology Research Group, University of Newcastle, Newcastle, New South Wales, Australia; South Asian Clinical Toxicology Research Collaboration (SACTRC), Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka.

ABSTRACT

Background: There is limited information on antivenom pharmacokinetics. This study aimed to investigate the pharmacokinetics of an Indian snake antivenom in humans with Russell's viper bites.

Methods/principal findings: Patient data and serial blood samples were collected from patients with Russell's viper (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 (40-70 y) 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 L h(-1), V,2.2L, Q,0.178 L h(-1) and VP,8.33L. The median half-life of distribution was 4.6 h (10-90%iles:2.6-7.1 h) and half-life of elimination, 140 h (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.

No MeSH data available.


Related in: MedlinePlus