PMID- 27999325 OWN - NLM STAT- MEDLINE DCOM- 20170913 LR - 20211117 IS - 1999-4915 (Electronic) IS - 1999-4915 (Linking) VI - 8 IP - 12 DP - 2016 Dec 17 TI - Pharmacokinetics of the Antiviral Lectin Griffithsin Administered by Different Routes Indicates Multiple Potential Uses. LID - 10.3390/v8120331 [doi] LID - 331 AB - Griffithsin (GRFT) is a red alga-derived lectin with demonstrated broad spectrum antiviral activity against enveloped viruses, including severe acute respiratory syndrome-Coronavirus (SARS-CoV), Japanese encephalitis virus (JEV), hepatitis C virus (HCV), and herpes simplex virus-2 (HSV-2). However, its pharmacokinetic profile remains largely undefined. Here, Sprague Dawley rats were administered a single dose of GRFT at 10 or 20 mg/kg by intravenous, oral, and subcutaneous routes, respectively, and serum GRFT levels were measured at select time points. In addition, the potential for systemic accumulation after oral dosing was assessed in rats after 10 daily treatments with GRFT (20 or 40 mg/kg). We found that parenterally-administered GRFT in rats displayed a complex elimination profile, which varied according to administration routes. However, GRFT was not orally bioavailable, even after chronic treatment. Nonetheless, active GRFT capable of neutralizing HIV-Env pseudoviruses was detected in rat fecal extracts after chronic oral dosing. These findings support further evaluation of GRFT for pre-exposure prophylaxis against emerging epidemics for which specific therapeutics are not available, including systemic and enteric infections caused by susceptible enveloped viruses. In addition, GRFT should be considered for antiviral therapy and the prevention of rectal transmission of HIV-1 and other susceptible viruses. FAU - Barton, Christopher AU - Barton C AD - Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA. christopher.barton@louisville.edu. FAU - Kouokam, J Calvin AU - Kouokam JC AD - Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA. j0kouo01@louisville.edu. FAU - Hurst, Harrell AU - Hurst H AD - Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA. hehurs01@louisville.edu. FAU - Palmer, Kenneth E AU - Palmer KE AD - Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA. kenneth.palmer@louisville.edu. AD - James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, USA. kenneth.palmer@louisville.edu. AD - Center for Predictive Medicine, University of Louisville School of Medicine, Louisville, KY 40202, USA. kenneth.palmer@louisville.edu. LA - eng GR - R01 AI076169/AI/NIAID NIH HHS/United States GR - T32 ES011564/ES/NIEHS NIH HHS/United States GR - U19 AI113182/AI/NIAID NIH HHS/United States GR - HHSN272201100016C/AI/NIAID NIH HHS/United States PT - Journal Article DEP - 20161217 PL - Switzerland TA - Viruses JT - Viruses JID - 101509722 RN - 0 (Antiviral Agents) RN - 0 (Plant Lectins) RN - Z8PX5UX50U (griffithsin protein, Griffithsia) SB - IM MH - Administration, Intravenous MH - Administration, Oral MH - Animals MH - Antiviral Agents/*administration & dosage/*pharmacokinetics MH - Biological Availability MH - Feces/chemistry MH - Injections, Subcutaneous MH - Plant Lectins/*administration & dosage/*pharmacokinetics MH - Rats, Sprague-Dawley MH - Serum/*chemistry MH - Time Factors PMC - PMC5192392 OTO - NOTNLM OT - Griffithsin OT - per os OT - pharmacokinetics OT - rat model OT - systemic administration COIS- Kenneth Palmer is a member of Intrucept Biomedicine LLC that holds a license to make and sell Griffithsin from the United States Public Health Service. The funding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results. EDAT- 2016/12/22 06:00 MHDA- 2017/09/14 06:00 PMCR- 2016/12/01 CRDT- 2016/12/22 06:00 PHST- 2016/10/11 00:00 [received] PHST- 2016/12/13 00:00 [revised] PHST- 2016/12/13 00:00 [accepted] PHST- 2016/12/22 06:00 [entrez] PHST- 2016/12/22 06:00 [pubmed] PHST- 2017/09/14 06:00 [medline] PHST- 2016/12/01 00:00 [pmc-release] AID - v8120331 [pii] AID - viruses-08-00331 [pii] AID - 10.3390/v8120331 [doi] PST - epublish SO - Viruses. 2016 Dec 17;8(12):331. doi: 10.3390/v8120331.