Pharmacokinetics of lurasidone, a novel atypical anti-psychotic drug, in rats

Abstract

1. This study aimed to characterise the pharmacokinetics of lurasidone, a new atypical anti-psychotic drug, in rats after intravenous and oral administration at dose range 0.5–2.5 and 2.5–10 mg/kg, respectively. Moreover, tissue distribution, liver microsomal stability and plasma protein binding were estimated.

2. After intravenous injection, systemic clearance, steady-state volumes of distribution and half-life remained unaltered as a function of dose with values in the range 22.1–27.0 mL/min/kg, 2,380–2,850 mL/kg and 229–267 min, respectively. Following oral administration, absolute oral bioavailability was not dose dependent with approximately 23%. The recoveries of lurasidone in urine and bile were 0.286% and 0.0606%, respectively.

3. Lurasidone was primarily distributed to nine tissues (brain, liver, kidneys, heart, spleen, lungs, gut, muscle and adipose) and tissue-to-plasma ratios of lurasidone were ranged from 1.06 (brain) to 9.16 (adipose). Further, lurasidone was unstable in rat liver microsome and the plasma protein binding of lurasidone was concentration independent with approximately 99.6%.

4. In conclusion, lurasidone showed dose-independent pharmacokinetics at an intravenous dose of 0.5–2.5 mg/kg and an oral dose of 2.5–10 mg/kg. Lurasidone was primarily distributed to nine tissues and appeared to be primarily eliminated by its metabolism.

Keywords::

• Lurasidone
• atypical anti-psychotic
• pharmacokinetics
• bioavailability
• tissue distribution
• metabolism