Enantioselective Effect of Flurbiprofen on Lithium Disposition in Rats

Pharmacology. 2017;99(5-6):236-239. doi: 10.1159/000455917. Epub 2017 Feb 2.

Abstract

Aims: Lithium is administered for treating bipolar disorders and is mainly excreted into urine. Nonsteroidal anti-inflammatory drugs inhibit this process. In this study, we examined the enantioselective effect of flurbiprofen on the disposition of lithium in rats.

Methods: Pharmacokinetic experiments with lithium were performed.

Results: Until 60 min after the intravenous administration of lithium chloride at 30 mg/kg as a bolus, 17.8% of lithium injected was recovered into the urine. Its renal clearance was calculated to be 1.62 mL/min/kg. Neither creatinine clearance (Ccr) nor pharmacokinetics of lithium was affected by the simultaneous injection of (R)-flurbiprofen at 20 mg/kg. (S)-flurbiprofen impaired the renal function and interfered with the urinary excretion of lithium. The ratio of renal clearance of lithium to Ccr was decreased by the (S)-enantiomer.

Conclusion: This study clarified that the (S)-flurbiprofen but not (R)-flurbiprofen inhibited the renal excretion of lithium in rats.

MeSH terms

  • Animals
  • Flurbiprofen / pharmacology*
  • Lithium Chloride / blood
  • Lithium Chloride / pharmacokinetics*
  • Lithium Chloride / urine
  • Male
  • Rats
  • Stereoisomerism

Substances

  • Flurbiprofen
  • Lithium Chloride