title: A phase I pharmacokinetic and safety evaluation of oral pazopanib dosing administered as crushed tablet or oral suspension in patients with advanced solid tumors.
abstract: Because cancer patients may have difficulty swallowing whole tablets, crushing tablets or ingesting an oral suspension is a practical alternative. This open-label, 2-part, randomized crossover, phase I study evaluated the pharmacokinetics and tolerability of pazopanib administered as a crushed tablet or an oral suspension relative to whole tablet in patients with advanced cancer (Part 1). Patients completing Part 1 were eligible for continuous daily pazopanib 800 mg (Part 2). Administration of a single pazopanib 400 mg crushed tablet increased the area under the curve from 0 to 72 h (AUC((0-72)); 46%) and maximum observed plasma concentration (C(max); ~2-fold), and decreased time to achieve maximum plasma concentration (T(max); ~2 h), indicating increased rate and extent of oral absorption relative to whole-tablet administration. Similarly, a single dose of pazopanib 400 mg suspension increased AUC((0-72)) (33%) and C(max) (29%), and decreased T(max) (1 h). These changes in pharmacokinetic parameters were not associated with increases in the magnitude or duration of short-term (ie, up to 72 h) blood pressure elevation compared with whole-tablet administration.
authors.affiliation: Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University, 4100 John R, Detroit, MI 48201, USA. heathe@karmanos.org
authors.forename: Elisabeth I
authors.initials: EI
authors.lastname: Heath
authors.forename: Karen
authors.initials: K
authors.lastname: Forman
authors.forename: Lisa
authors.initials: L
authors.lastname: Malburg
authors.forename: Shelby
authors.initials: S
authors.lastname: Gainer
authors.forename: A Benjamin
authors.initials: AB
authors.lastname: Suttle
authors.forename: Laurel
authors.initials: L
authors.lastname: Adams
authors.forename: Howard
authors.initials: H
authors.lastname: Ball
authors.forename: Patricia
authors.initials: P
authors.lastname: LoRusso
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D003710:Demography; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007191:Indazoles; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013535:Suspensions; D013607:Tablets; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007191:Indazoles; D011743:Pyrimidines; D013449:Sulfonamides; D013535:Suspensions; D013607:Tablets; C516667:pazopanib