{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:55:40Z","timestamp":1787061340279,"version":"build-2736575974"},"reference-count":57,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T00:00:00Z","timestamp":1594944000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005739","name":"Universidad Nacional Aut\u00f3noma de M\u00e9xico","doi-asserted-by":"publisher","award":["PAPIIT-DGAPA IN207218"],"award-info":[{"award-number":["PAPIIT-DGAPA IN207218"]}],"id":[{"id":"10.13039\/501100005739","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["Venenos y antivenenos 303045, Fondo Institucional de Fomento Regional para el Desarrollo Cient\u00edfico, Tecnol\u00f3gico y de Innovaci\u00f3n (FORDECYT), Mexico"],"award-info":[{"award-number":["Venenos y antivenenos 303045, Fondo Institucional de Fomento Regional para el Desarrollo Cient\u00edfico, Tecnol\u00f3gico y de Innovaci\u00f3n (FORDECYT), Mexico"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>The most abundant protein families in viper venoms are Snake Venom Metalloproteases (SVMPs), Snake Venom Serine Proteases (SVSPs) and Phospholipases (PLA2s). These are primarily responsible for the pathophysiology caused by the bite of pit-vipers; however, there are few studies that analyze the pharmacokinetics (PK) of whole venom (WV) and its protein families. We studied the pathophysiology, PK profile and differential absorption of representative toxins from venom of Neotropical Rattlesnake (Crotalus simus) in a large animal model (ovine). Toxins studied included crotoxin (the main lethal component), which causes moderate to severe neurotoxicity; SVSPs, which deplete fibrinogen; and SVMPs, which cause local tissue damage and local and systemic hemorrhage. We found that Whole Venom (WV) was highly bioavailable (86%) 60 h following intramuscular (IM) injection, and extrapolation suggests that bioavailability may be as high as 92%. PK profiles of individual toxins were consistent with their physicochemical properties and expected clinical effects. Lymph cannulated animals absorbed 1.9% of WV through lymph during the first 12 h. Crotoxin was minimally detectable in serum after intravenous (IV) injection; however, following IM injection it was detected in lymph but not in blood. This suggests that crotoxin is quickly released from the blood toward its tissue targets.<\/jats:p>","DOI":"10.3390\/toxins12070455","type":"journal-article","created":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T05:10:30Z","timestamp":1595394630000},"page":"455","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Neotropical Rattlesnake (Crotalus simus) Venom Pharmacokinetics in Lymph and Blood Using an Ovine Model"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1551-4584","authenticated-orcid":false,"given":"Edgar","family":"Neri-Castro","sequence":"first","affiliation":[{"name":"Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnologia, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Av. Universidad 2001, Cuernavaca 62210, Mexico"},{"name":"Programa de Doctorado en Ciencias Biom\u00e9dicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Unidad de Posgrado, Edificio B Primer Piso, Ciudad Universitaria, Ciudad de M\u00e9xico 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0042-6592","authenticated-orcid":false,"given":"Melisa","family":"B\u00e9nard-Valle","sequence":"additional","affiliation":[{"name":"Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnologia, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Av. Universidad 2001, Cuernavaca 62210, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dayanira","family":"Paniagua","sequence":"additional","affiliation":[{"name":"Facultad de Ingenier\u00eda, Arquitectura y Dise\u00f1o, Universidad Aut\u00f3noma de Baja California, Ensenada, Baja California 22860, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie","family":"V. Boyer","sequence":"additional","affiliation":[{"name":"Venom Immunochemistry, Pharmacology, and Emergency Response (VIPER) Institute, University of Arizona,1501 N. Campbell Avenue, Tucson, AZ 85724, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6357-2661","authenticated-orcid":false,"given":"Lourival","family":"D. Possani","sequence":"additional","affiliation":[{"name":"Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnologia, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Av. Universidad 2001, Cuernavaca 62210, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"L\u00f3pez-Casillas","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda Celular, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Ciudad Universitaria, Ciudad de M\u00e9xico 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Olvera","sequence":"additional","affiliation":[{"name":"Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnologia, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Av. Universidad 2001, Cuernavaca 62210, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilo","family":"Romero","sequence":"additional","affiliation":[{"name":"Centro Universitario UAEM Amecameca, Universidad Aut\u00f3noma del Estado de M\u00e9xico, Amecameca de Ju\u00e1rez 56900, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Zamudio","sequence":"additional","affiliation":[{"name":"Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnologia, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Av. Universidad 2001, Cuernavaca 62210, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Alag\u00f3n","sequence":"additional","affiliation":[{"name":"Departamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnologia, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Av. Universidad 2001, Cuernavaca 62210, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,17]]},"reference":[{"key":"ref_1","unstructured":"Peter Uetz, J.H. (2020, June 02). The Reptile Database. Available online: http:\/\/www.reptile-database.org."},{"key":"ref_2","unstructured":"Campbell, J., and Lamar, W.W. (2004). The Venomous Reptiles of the Western Hemisphere, Cornell University Press."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1111\/j.1365-294X.2005.02471.x","article-title":"Tracing an invasion: Landbridges, refugia, and the phylogeography of the Neotropical rattlesnake (Serpentes: Viperidae: Crotalus durissus)","volume":"14","author":"Ferguson","year":"2005","journal-title":"Mol. Ecol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.jprot.2013.05.024","article-title":"Intraspecies variation in the venom of the rattlesnake Crotalus simus from Mexico: Different expression of crotoxin results in highly variable toxicity in the venoms of three subspecies","volume":"87","author":"Castro","year":"2013","journal-title":"J. Proteom."},{"key":"ref_5","first-page":"451","article-title":"Accessing cryptic diversity in Neotropical rattlesnakes (Serpentes: Viperidae: Crotalus) with the description of two new species","volume":"4729","author":"Rabet","year":"2020","journal-title":"Zootaxa"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1021\/pr9008749","article-title":"Snake Venomics of the Central American Rattlesnake Crotalus simus and the South American Crotalus durissus Complex Points to Neurotoxicity as an Adaptive Paedomorphic Trend along Crotalus Dispersal in South America","volume":"9","author":"Calvete","year":"2010","journal-title":"J. Proteome Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3370","DOI":"10.1021\/acs.jproteome.7b00414","article-title":"Integrated Venomics and Venom Gland Transcriptome Analysis of Juvenile and Adult Mexican Rattlesnakes Crotalus simus, C. tzabcan, and C. culminatus Revealed miRNA-modulated Ontogenetic Shifts","volume":"16","author":"Durban","year":"2017","journal-title":"J. Proteome Res."},{"key":"ref_8","first-page":"337","article-title":"Geographic and ontogenic variability in the venom of the neotropical rattlesnake Crotalus durissus: Pathophysiological and therapeutic implications","volume":"50","author":"Saravia","year":"2002","journal-title":"Rev. Biol. Trop."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.jprot.2017.02.015","article-title":"Proteomic, toxicological and immunogenic characterization of Mexican west-coast rattlesnake (Crotalus basiliscus) venom and its immunological relatedness with the venom of Central American rattlesnake (Crotalus simus)","volume":"158","author":"Segura","year":"2017","journal-title":"J. Proteom."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"100007","DOI":"10.1016\/j.toxcx.2019.100007","article-title":"Detection and quantification of a \u03b2-neurotoxin (crotoxin homologs) in the venom of the rattlesnakes Crotalus simus, C. culminatus and C. tzabcan from Mexico","volume":"2","author":"Bastiaans","year":"2019","journal-title":"Toxicon X"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"8074","DOI":"10.1021\/bi00246a028","article-title":"Multiplicity of Acidic Subunit Isoforms of Crotoxin, the Phospholipase A2 Neurotoxin from Crotalus durissus terrificus Venom, Results from Posttranslational Modifications","volume":"30","author":"Faure","year":"1991","journal-title":"Biochemistry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1111\/j.1432-1033.1993.tb17946.x","article-title":"Comparison of crotoxin isoforms reveals that stability of the complex plays a major role in its pharmacological action","volume":"214","author":"Faure","year":"1993","journal-title":"Eur. J. Biochem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/j.1432-1033.1994.tb18978.x","article-title":"The origin of the diversity of crotoxin isoforms in the venom of Crotalus durissus terrificus","volume":"223","author":"Faure","year":"1994","journal-title":"Eur. J. Biochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.jmb.2011.07.027","article-title":"Crystal structure of crotoxin reveals key residues involved in the stability and toxicity of this potent heterodimeric \u03b2-neurotoxin","volume":"412","author":"Faure","year":"2011","journal-title":"J. Mol. Biol."},{"key":"ref_15","first-page":"377","article-title":"Comprendiendo los venenos de serpientes: 50 A\u00f1os de investigaciones en Am\u00e9rica Latina","volume":"50","year":"2002","journal-title":"Rev. Biol. Trop."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1023\/A:1015880819328","article-title":"Effect of Molecular Weight on the Lymphatic Absorption of Water-Soluble Compounds Following Subcutaneous Administration","volume":"7","author":"Supersaxo","year":"1990","journal-title":"Pharm. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/j.toxicon.2005.02.012","article-title":"Structural considerations of the snake venom metalloproteinases, key members of the M12 reprolysin family of metalloproteinases","volume":"45","author":"Fox","year":"2005","journal-title":"Toxicon"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/S0300-9084(00)01163-9","article-title":"Snake venom metalloproteinases: Their role in the pathogenesis of local tissue damage","volume":"82","author":"Rucavado","year":"2000","journal-title":"Biochimie"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.bbapap.2011.04.009","article-title":"Snake venom metalloproteinases: Structure, function and relevance to the mammalian ADAM\/ADAMTS family proteins","volume":"1824","author":"Takeda","year":"2012","journal-title":"Biochim. Biophys. Acta Proteins Proteom."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1067\/mem.2001.113134","article-title":"Recurrence phenomena after immunoglobulin therapy for snake envenomations: Part 2. Guidelines for clinical management with crotaline fab antivenom","volume":"37","author":"Boyer","year":"2001","journal-title":"Ann. Emerg. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.toxicon.2013.02.008","article-title":"Continuous IV Crotalidae Polyvalent Immune Fab (Ovine) (FabAV) for selected North American Rattlesnake bite patients","volume":"69","author":"Bush","year":"2013","journal-title":"Toxicon"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/S0041-0101(02)00393-8","article-title":"Report of a WHO workshop on the standardization and control of antivenoms","volume":"41","author":"Theakston","year":"2003","journal-title":"Toxicon"},{"key":"ref_23","first-page":"1512","article-title":"Pharmacokinetics of Vipera aspis venom after experimental envenomation in rabbits","volume":"268","author":"Audebert","year":"1994","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/0041-0101(88)90009-8","article-title":"Body distribution of Bothrops asper (terciopelo) snake venom myotoxin and its relationship to pathological changes","volume":"26","author":"Moreno","year":"1988","journal-title":"Toxicon"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1016\/j.intimp.2013.10.007","article-title":"Pharmacokinetics of Cryptelytrops purpureomaculatus (mangrove pit viper) venom following intravenous and intramuscular injections in rabbits","volume":"17","author":"Sim","year":"2013","journal-title":"Int. Immunopharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.toxicon.2013.12.011","article-title":"Pharmacokinetics of the Sri Lankan hump-nosed pit viper (Hypnale hypnale) venom following intravenous and intramuscular injections of the venom into rabbits","volume":"79","author":"Tan","year":"2014","journal-title":"Toxicon"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Sanhajariya, S., Duffull, S.B., and Isbister, G.K. (2018). Pharmacokinetics of snake venom. Toxins, 10.","DOI":"10.3390\/toxins10020073"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Yap, M.K.K., Tan, N.H., Sim, S.M., Fung, S.Y., and Tan, C.H. (2014). Pharmacokinetics of Naja sumatrana (Equatorial Spitting Cobra) Venom and Its Major Toxins in Experimentally Envenomed Rabbits. PLoS Negl. Trop. Dis., 8.","DOI":"10.1371\/journal.pntd.0002890"},{"key":"ref_29","first-page":"144","article-title":"Lymphatic route of transport and pharmacokinetics of Micrurus fulvius (coral snake) venom in sheep","volume":"45","author":"Paniagua","year":"2012","journal-title":"Lymphology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.toxicon.2013.07.018","article-title":"Subacute coagulopathy in a randomized, comparative trial of Fab and F(ab\u2019)2 antivenoms","volume":"74","author":"Boyer","year":"2013","journal-title":"Toxicon"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"721","DOI":"10.2165\/00003088-200342080-00002","article-title":"Pharmacokinetic-Pharmacodynamic Relationships of Immunoglobulin Therapy for Envenomation","volume":"42","author":"Gutierrez","year":"2003","journal-title":"Clin. Pharmacokinet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/S0196-0644(96)70267-6","article-title":"Validation of a severity score for the assessment of crotalid snakebite","volume":"27","author":"Dart","year":"1996","journal-title":"Ann. Emerg. Med."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Lavonas, E.J., Gerardo, C.J., Arcuri, K., Daugherty, C.A., Temu, A., Anderson, V.E., Bartelson, B.B., Coulter, M.S., Gillman, S.M., and Goodman, E.M. (2015). Prospective study of recovery from copperhead snake envenomation: An observational study. BMC Emerg. Med., 15.","DOI":"10.1186\/s12873-015-0033-6"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"604","DOI":"10.3109\/15563650.2014.914526","article-title":"Pharmacokinetics and pharmacodynamics of the myotoxic venom of Pseudechis australis (mulga snake) in the anesthetised rat","volume":"52","author":"Hart","year":"2014","journal-title":"Clin. Toxicol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Borja, M., Neri-Castro, E., Casta\u00f1eda-Gayt\u00e1n, G., Strickland, J.L., Parkinson, C.L., Casta\u00f1eda-Gayt\u00e1n, J., Ponce-L\u00f3pez, R., Lomonte, B., Olvera-Rodr\u00edguez, A., and Alag\u00f3n, A. (2018). Biological and proteolytic variation in the venom of crotalus scutulatus scutulatus from Mexico. Toxins, 10.","DOI":"10.3390\/toxins10010035"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15563650.2018.1550199","article-title":"Antivenom effect on lymphatic absorption and pharmacokinetics of coral snake venom using a large animal model","volume":"57","author":"Paniagua","year":"2019","journal-title":"Clin. Toxicol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.biochi.2014.01.008","article-title":"Understanding structural and functional aspects of PII snake venom metalloproteinases: Characterization of BlatH1, a hemorrhagic dimeric enzyme from the venom of Bothriechis lateralis","volume":"101","author":"Camacho","year":"2014","journal-title":"Biochimie"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/0041-0101(94)00138-X","article-title":"Isolation and characterization of a metalloproteinase with weak hemorrhagic activity from the venom of the snake Bothrops asper (terciopelo)","volume":"33","author":"Romero","year":"1995","journal-title":"Toxicon"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pntd.0003731","article-title":"Tissue Localization and Extracellular Matrix Degradation by PI, PII and PIII Snake Venom Metalloproteinases: Clues on the Mechanisms of Venom-Induced Hemorrhage","volume":"9","author":"Herrera","year":"2015","journal-title":"PLoS Negl. Trop. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1002\/jcph.4","article-title":"The antibody drug absorption following subcutaneous or intramuscular administration and its mathematical description by coupling physiologically based absorption process with the conventional compartment pharmacokinetic model","volume":"53","author":"Zhao","year":"2013","journal-title":"J. Clin. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Helden, D.F., Van Dosen, P.J., Leary, M.A.O., and Isbister, G.K. (2019). Two pathways for venom toxin entry consequent to injection of an Australian elapid snake venom. Sci. Rep., 1\u201310.","DOI":"10.1038\/s41598-019-45022-4"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1055\/s-0037-1614964","article-title":"Snake venom fibrinogenolytic and fibrinolytic enzymes: An updated inventory. Registry of Exogenous Hemostatic Factors of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis","volume":"79","author":"Markland","year":"1998","journal-title":"Thromb. Haemost."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Fox, J.W., and Guti\u00e9rrez, J.M. (2017). Understanding the snake venom metalloproteinases: An interview with jay fox and jos\u00e9 mar\u00eda guti\u00e9rrez. Toxins, 9.","DOI":"10.3390\/toxins9010033"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Guti\u00e9rrez, J.M., Escalante, T., Rucavado, A., Herrera, C., and Fox, J.W. (2016). A comprehensive view of the structural and functional alterations of extracellular matrix by snake venom metalloproteinases (SVMPs): Novel perspectives on the pathophysiology of envenoming. Toxins, 8.","DOI":"10.3390\/toxins8100304"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"D506","DOI":"10.1093\/nar\/gky1049","article-title":"UniProt: A worldwide hub of protein knowledge","volume":"47","author":"Bateman","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/0041-0101(91)90028-P","article-title":"Serum kinetics of crotoxin from Crotalus durissus terrificus venom in mice: Evidence for a rapid clearance","volume":"29","year":"1991","journal-title":"Toxicon"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Mora, J., Mora, R., Lomonte, B., and Guti\u00e9rrez, J.M. (2008). Effects of Bothrops asper snake venom on lymphatic vessels: Insights into a hidden aspect of envenomation. PLoS Negl. Trop. Dis., 2.","DOI":"10.1371\/journal.pntd.0000318"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"100013","DOI":"10.1016\/j.toxcx.2019.100013","article-title":"Biochemical and immunochemical characterization of venoms from snakes of the genus Agkistrodon","volume":"4","author":"Archundia","year":"2019","journal-title":"Toxicon X"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/227680a0","article-title":"Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4","volume":"227","author":"Laemmli","year":"1970","journal-title":"Nature"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/BF01234480","article-title":"A new approach to practical acute toxicity testing","volume":"54","author":"Lorke","year":"1983","journal-title":"Arch. Toxicol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.toxicon.2009.01.011","article-title":"Paraspecific neutralization of the venom of African species of cobra by an equine antiserum against Naja melanoleuca: A comparative study","volume":"53","author":"Casasola","year":"2009","journal-title":"Toxicon"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1096\/fasebj.1.5.3315805","article-title":"Fitting curves nonlinear regression: Review a practical","volume":"1","author":"Motulsky","year":"1987","journal-title":"FASEB J."},{"key":"ref_53","first-page":"949","article-title":"Development of simple standard assay procedures for the characterization of snake venoms","volume":"61","author":"Theakston","year":"1983","journal-title":"Bull. W. Health Organ."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/0041-0101(85)90380-0","article-title":"Neutralization of proteolytic and hemorrhagic activities of Costa Rican snake venoms by a polyvalent antivenom","volume":"23","author":"Rodas","year":"1985","journal-title":"Toxicon"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1586\/epr.11.61","article-title":"Proteomic tools against the neglected pathology of snake bite envenoming","volume":"8","author":"Calvete","year":"2011","journal-title":"Expert Rev. Proteom."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/j.toxicon.2012.01.005","article-title":"Snake venomics and toxicological profiling of the arboreal pitviper Bothriechis supraciliaris from Costa Rica","volume":"59","author":"Lomonte","year":"2012","journal-title":"Toxicon"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.cmpb.2010.01.007","article-title":"PKSolver: An add-in program for pharmacokinetic and pharmacodynamic data analysis in Microsoft Excel","volume":"99","author":"Zhang","year":"2010","journal-title":"Comput. Methods Progr. Biomed."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/12\/7\/455\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:49:16Z","timestamp":1760176156000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/12\/7\/455"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,17]]},"references-count":57,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2020,7]]}},"alternative-id":["toxins12070455"],"URL":"https:\/\/doi.org\/10.3390\/toxins12070455","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,17]]}}}