title: Clinical pharmacokinetics of panobinostat, a novel histone deacetylase (HDAC) inhibitor: review and perspectives.
abstract: 1. Panobinostat is a recently approved histone deacetylase (HDAC) inhibitor. 2. The pharmacokinetic data of panobinostat in patients with hematologic malignancies and advanced solid tumors have been collated and reviewed from the various published clinical studies for over a decade. Further perspectives and anticipated challenges in the clinical therapy with panobinostat are discussed in the review. 3. Regardless of intravenous or oral dosing, panobinostat showed a high degree of inter-patient variability in the pharmacokinetics. After oral administration, most of the administered dose is extensively metabolized and the metabolites are either fecally or renally excreted with trace amount of intact panobinostat. Both cytochrome p450 (CYP) 3A4 and non-CYP mechanisms govern the clearance of panobinostat. CYP3A4-related drug-drug interactions with panobinostat have been documented with ketoconazole (inhibitor) and dexamethasone (inducer). 4. In summary, the clinical pharmacokinetic data of panobinostat, a promising HDAC inhibitor, obtained from various clinical studies do not appear to limit the utility of panobinostat in the clinic.
authors.affiliation: a Department of Drug Development, Suramus Bio , Bangalore, Karnataka , India.
authors.forename: Nuggehally R
authors.initials: NR
authors.lastname: Srinivas
mesh_terms: D051544:Cytochrome P-450 CYP3A; D003907:Dexamethasone; D004347:Drug Interactions; D056572:Histone Deacetylase Inhibitors / Q000493:pharmacokinetics*; D006877:Hydroxamic Acids / Q000493:pharmacokinetics*; D007211:Indoles / Q000493:pharmacokinetics*; D007654:Ketoconazole; D000077767:Panobinostat
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; D003907:Dexamethasone; D000077767:Panobinostat; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D007654:Ketoconazole
keywords: Cancer; HDAC inhibitors; clinical pharmacokinetics; drug combination; drug–drug interaction; panobinostat; review