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Population Pharmacokinetics of an Indian F(ab')2 Snake Antivenom in Patients with Russell's Viper (Daboia russelii) Bites
- Source :
- PLoS Neglected Tropical Diseases, PLoS Neglected Tropical Diseases, Vol 9, Iss 7, p e0003873 (2015)
- Publication Year :
- 2015
- Publisher :
- Public Library of Science (PLoS), 2015.
-
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 (40-70y) 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.<br />Author Summary Snake envenoming is a neglected tropical disease that affects hundreds of thousands of people in the rural tropics. Antivenom is the main treatment for snake bites but there is limited information on the pharmacokinetics and appropriate dosing regimen. Most studies have been done in animals and dosing guidelines are based on arbitrary and often irreversible clinical signs. In this study we measured serial antivenom concentrations in patients with Russell’s viper envenoming given antivenom. Using this data we modelled the pharmacokinetics of antivenom in the population and showed that antivenom concentrations had a bi-exponential decay with an initial decrease over 12 hours and then a slow decrease over days. There was significant variability in the dose given which was not affected by the particular antivenom batch given. The presence of venom did not appear to modify the pharmacokinetics of antivenom. Understanding the time course of antivenom in patients with snake envenoming will provide a better basis for antivenom dosing.
- Subjects :
- Adult
Male
Veterinary medicine
lcsh:Arctic medicine. Tropical medicine
VIPeR
lcsh:RC955-962
030231 tropical medicine
Antivenom
Snake Bites
Viper Venoms
Population pharmacokinetics
qv_38
complex mixtures
Immunoglobulin Fab Fragments
03 medical and health sciences
0302 clinical medicine
Animals
Humans
Medicine
Russell's Viper
In patient
030212 general & internal medicine
Snake antivenom
Aged
Sri Lanka
Traditional medicine
Antivenins
business.industry
lcsh:Public aspects of medicine
Public Health, Environmental and Occupational Health
lcsh:RA1-1270
Middle Aged
3. Good health
Pharmacokinetic analysis
Kinetics
Infectious Diseases
qv_601
Female
business
wd_410
Research Article
Subjects
Details
- ISSN :
- 19352735
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- PLOS Neglected Tropical Diseases
- Accession number :
- edsair.doi.dedup.....f8c0f03cd480a930e74f41849ccf3aed