A phase I pharmacokinetic and safety evaluation of oral pazopanib dosing administered as crushed tablet or oral suspension in patients with advanced solid tumors

作者：Heath Elisabeth I^*; Forman Karen; Malburg Lisa; Gainer Shelby; Suttle A Benjamin; Adams Laurel; Ball Howard; LoRusso Patricia

来源：Investigational New Drugs, 2012, 30(4): 1566-1574.

DOI：10.1007/s10637-011-9725-2

• Pazopanib
• Pharmacokinetics
• Crushed tablet
• Oral suspension

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; similar to 2-fold), and decreased time to achieve maximum plasma concentration (T-max; similar to 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.

• 出版日期2012-8