Toxicology

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Introduction

Branches of Toxicology

Comparative Toxicogenomics

Comparative Toxicogenomics




Databases

Sample Example

Cyclopropavir (CPV,ZSM-I-62,MBX400)has been shown to be potent against beta-and gamma-herpes viruses Here is the study conducted to test the toxicology and pharmacokinetics of this active on rat

Summary of Primary Pharmacokinetic, Toxicokineticand Toxicology Studies
Species (Strain) Study Type Route Dose (mg/kg) No. of Animals per Sex GLP?
M F
Rat (Sprague Dawley) Single Dose Pharmacokinetic i.v. 10 9 - No
    oral 1 9 -  
      5 9 -  
      10 9 -  
  Single Dose Acute Toxicity Oral 0 5 5 Yes
      50 5 5  
      100 5 5  
      300 5 5  
  14-Day Toxicity/Toxicokinetic Oral 0 15 + 9 TK 15 + 9 TK Yes
      10 10 + 9 TK 10 + 9 TK  
      50 10 + 9 TK 10 + 9 TK  
      100 15 + 9 TK 15 + 9 TK  


Single-Dose Pharmacokinetic and ToxicokineticParameters
Species (Strain) Study Route Dose (mg/kg) No. of Animals AUC0-?(ng?hr/mL) t1/2(hr) Cmax(ng/mL) Tmax(hr) F (%)
M F
Rat (Sprague Dawley) Single Dose PK i.v. 10 9 - 10735 2.34 14500 0.083 -
    Oral 1 9 - 494 1.09 262 0.5 46.0
      5 9 - 1638 1.23 590 0.5 30.5
      10 9 - 2435 1.12 739 0.5 22.7
  14-Day Toxicity/TK Oral 10 9 - 2413 1.51 612 1.00 -
        - 9 1843 3.74 682 0.50 -
      50 9 - 7671a ND 1517 2.00 -
        - 9 7055 3.08 1131 2.00 -
      100 9 - 11749 3.30 1763 1.00 -
        - 9 9129a ND 1175 4.00 -


Selected Hematology Data from Rat Single-Dose -Escalating Toxicology Studies
Species (Strain) Sex Dose (mg/kg)a Red Blood Cell Count(1x106/?L) Hemoglobin (g/dL) Hematocrit(%) Mean Corpuscular Volume (femtoliter) Mean Corpuscular Hemoglobin (pg) Mean Corpuscular Hemoglobin Conc. (g/dL) Reticulocytes(1x103/?L) Platelets (1x103/?L) White Blood Cell Count (1x103/?L) Neutrophils (1x103/?L) Lymphocytes(1x103/?L)
Rat (Sprague Dawley)b M 0 6.94±0.221 14.3 ±0.48 44.5 ±1.89 64.1 ±1.52 20.6 ±0.36 32.2 ±0.33 544.5 ±30.82 1448 ±288.8 7.15 ±0.885 0.71±0.214 6.19 ±0.984
    300 7.27 ±0.537 14.7 ±0.70 48.0 ±3.02 63.4 ±2.37 20.2 ±0.81 31.9 ±0.80 503.3 ±67.80 1228 ±201.6 6.42 ±1.189 0.79 ±0.338 5.32 ±1.153
  F 0 7.29 ±0.150 14.8 ±0.23 44.7 ±0.58 61.2 ±0.58 20.3 ±0.25 33.2 ±0.24 353.2 ±10.97 1328 ±104.2 6.24 ±1.442 0.75 ±0.233 5.15 ±1.443
    300 7.55 ±0.185 15.2 ±0.28 45.6 ±1.11 60.4 ±4.41 20.1 ±0.52 33.3 ±0.38 333.0 ±52.44 1245 ±166.6 7.66 ±1.944 0.63 ±0.374 6.70 ±1.693


Safety Pharmacology Studies
Species (Strain) Study Type Route Dose (mg/kg) No. of Animals GLP? Results
M F
Rat (Sprague Dawley) Central Nervous System Oral 0 6 6 Yes Cyclopropavirhad no effect on clinical signs, body weight or Irwintest results
      10 6 6    
      50 6 6    
      100 6 6    


Selected Clinical Chemistry Data from Rat Single-Dose Escalating Toxicology Studies
Species (Strain) Sex Dose (mg/kg) Urea Nitrogen (mg/dL) Creatinine(mg/dL) Total Protein (g/dL) Albumin (g/dL) Globulin (g/dL) Albumin Globulin Ratio Calcium (mg/dL) Phosphorus (mg/dL) Sodium (mmol/L) Potassium(mmol/L)
Rat (Sprague Dawley)a,b M 0 14 ±1.1 0.5±0.00 5.7 ±0.24 4.0 ±0.12 1.7 ±0.05 2.4 ±0.09 10.8 ±0.11 11.0 ±0.51 147 ±1.3 5.8 ±0.31
    300 13 ±1.3 0.5 ±0.00 5.8 ±0.43 4.1 ±0.12 1.7 ±0.11 2.4 ±0.13 10.9 ±0.28 10.6 ±0.27 148 ±1.6 5.8 ±0.37
  F 0 15 ±1.3 0.6 ±0.05 6.0 ±0.18 4.4 ±0.05 1.7 ±0.18 2.7 ±0.31 11.1 ±0.30 9.5 ±0.40 147 ±1.0 5.4 ±0.4
    300 15 ±2.3 0.5 ±0.04 6.1 ±0.18 4.6 ±0.08 1.6 ±0.17 3.0 ±0.35 11.3 ±0.11 9.7 ±0.72 147 ±2.3 5.5 ±0.5

Summary

Pharmacokinetic data (plasma)

Toxicokineticdata (plasma)

Toxicology studies