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 |