Skip to main content

Advertisement

Table 3 FDA and EMA drug description of anticancer drugs of lead compounds

From: Repurposing of anticancer drugs: in vitro and in vivo activities against Schistosoma mansoni

Drug Cmax Single oral dose (or otherwise as indicated) t1/2 Single oral dose (or otherwise as indicated) LD50 Single oral dose toxicity Indication Mechanism of action Dosage Reference (health agency)
Afatinib (GIOTRIF®) NA 37 h (after repeated dosing given to patients) NA Metastatic non-small cell lung cancer Irreversible inhibitor of tyrosine kinase autophos-phorylation 40 mg/day FDA
  397 nmol/l (1×8 mg/kg given to rats) 4.5 h (1×8 mg/kg given to rats) 382–763 mg/kg (mice) EMA
Bosutinib (BOSULIF®) 0.2 μg/ml (500 mg given to patients on 15 consecutive days) 22 h (patients; dose not indicated) NA Chronic, accelerated, or blast phase Ph + chronic myelogenous leukemia Tyrosine kinase inhibitor 500 mg/day FDA
  NA 2.5–5.4 h (mice and rats; dose not indicated) >2000 mg/kg (mice and rats) EMA
Crizotinib (XALKORI®) 100–135 ng/ml (250 mg given to patients) 42 h (250 mg given to patients) >500 mg/kg (rats) Metastatic non-small cell lung cancer Tyrosine kinase inhibitor 2×250 mg/day FDA
  NA 5.8–13 h (rats; dose not indicated) NA EMA
Gefitinib (IRESSA®) NA 48 h (healthy volunteers; dose not indicated) NA Non-small cell lung cancer Multiple tyrosine kinase inhibitor 250 mg/day FDA
  1 μg/ml (after 20 mg/kg given to rats); 0.1 μg/ml (after 250 mg/kg given to healthy volunteers) 10 h (rats; dose not indicated); 30 h (after 250 mg/kg given to healthy volunteers) Around 2000 mg/kg (rats); >1000 mg/kg (dogs) EMA
Ponatinib (INCLUSIG®) 6 h (patients; dose not indicated) 24 h (patients; dose not indicated) >2000 mg/kg (mice) Chronic myeloid leukemia Tyrosine kinase inhibitor 45 mg/day FDA
  4 h (patients; dose not indicated) 22 h (patients; dose not indicated) NA EMA
Regorafenib (STIVAGRA®) 12.5 μg/ml (after 160 mg given to patients) 24 h (after 160 mg given to patients) NA Metastatic colon cancer Multiple protein kinase inhibitor 160 mg/day for first 21 days of a 28-day cycle FDA
  3.96 mg/l (multiple treatment: 160 mg/day for 3 weeks given to patients) 2 h (multiple treatment; 160 mg/day for 3 weeks given to patients) >250 mg/kg (mice and rats)   EMA
Sorafenib (NEXAVAR®) NA 25–48 h NA Liver, kidney, thyroid cancer Multiple protein kinase inhibitor 2×400 mg/day FDA
  0.55 mg/l (after 400 mg given to patients) 22.3 h (after 400 mg given to patients) >1460 mg/kg (mice and rats) EMA
Sunitinib (SUTENT®) NA 40–60 h (parent drug in healthy volunteers; 80–110 h (active metabolite in healthy volunteers (dose not indicated) NA Gastrointestinal stromal tumor, renal cell carcinoma, well-differentiated pancreatic neuroendocrine tumors Inhibitor of multiple receptor tyrosine kinases 50 mg/d for the first 28 days of a 42-day cycle FDA
  NA NA >500 mg/kg (mice and rats) EMA
Trametinib (MEKINIST®) NA Estimated: 3.9–4.8 days (patients; dose not indicated) NA Unresectable or metastatic melanoma with BRAF V600E or V600K mutations Kinase inhibitor 2 mg/day FDA
  22.2 ng/ml (steady state after 2 mg/daygiven to healthy volunteers) 5.3 days (healthy volunteers; dose not indicated) NA EMA
Tamoxifen citrate (NOLVADEX®) 40 ng/ml (after 20 mg given to rats) 5–6 days (after 20 mg given to rats) NA Breast cancer Nonsteroidal antiestrogen NA FDA
  NA NA NA 20 mg/day EMA
Vandetanib (CAPRELSA®) NA NA NA Medullary thyroid cancer Multiple tyrosine kinase inhibitor 300 mg/day FDA
  NA 19 days (after 300 mg given to healthy volunteers) NA EMA
  1. NA Not available on the data sheets of the according health agency