| Abstrakt: |
The major toxicities/target organs observed for each drug class in nonclinical species included: 1) endocrine disruption and liver toxicities for SARMs; 2) gonadal and liver toxicities for myostatin inhibitors; 3) cardiac and renal toxicities for calcium modulators; 4) renal, neurological, and gastrointestinal toxicities for immunosuppressants; and 5) liver, spleen, and bone marrow toxicities for antioxidants. The US Food and Drug Administration (FDA) has been approving a growing diversity of new chemical modalities, including small interfering RNA (siRNA) drugs, antisense oligonucleotides, antibody drug conjugates, fluorine atoms and/or nitrogen aromatic heterocycles, pegylated peptides, I etc. i Just last year, FDA approved 14 new biologics and 27 first-in-class drugs which employ a mode of action that is different from existing therapies. P415: In Vitro Predictive Toxicity Screening Assays during Early Stage Drug Development: Case... Sebastien Breche 1, Elise Esneault1, Sonia Goineau-Brissieux1, Florian Simon1, Christophe Leg... 1Porsolt S.A.S., Le Genest St Isle, Mayenne, France Drug induced toxicity is responsible for a significant proportion of drug attrition and costly withdrawal during late-stage development. The NOEL was established at 200-fold higher than the predicted human total ligand mass dose of 60 µg for the diagnostic drug and 25-fold for the radiotherapeutic drug dose of 500 µg. The preclinical package also included a dog biodistribution and dosimetry study using radiolabeled DPI-4452. Maximum plasma concentration and plasma exposure was dose proportional at lower doses and less than dose proportional at higher doses. [Extracted from the article] |
