Increased lithium serum and red blood cell concentrations during ketorolac coadministration

Case reports of a lithium-ketorolac drug interaction have been published, but no formal investigation of this interaction has been conducted. The objective of the study presented here was to determine significant changes in lithium serum and red blood cell (RBC) concentrations after lithium and ketorolac (oral formulation) coadministration at steady-state conditions. Five healthy men participated in the study and received lithium 900 mg/day (300 mg in the morning and 600 mg at bedtime) for 13 days. Ketorolac 40 mg/day (10 mg four times a day) was added on days 8 through 12. Ten blood samples were obtained on days 7 and 13 to determine area under the concentration-time curve (AUC) lithium serum and RBC concentrations. Serum and RBC lithium concentrations were assayed by atomic absorption spectrophotometry with an intra-assay coefficient of variation (CV) of 1.2% on day 1 (range 0-1.0 microg/mL) and 4.9% (range 0-1.0 microg/mL) on day 2 and an interassay CV of 2.9% (range 0-1.0 microg/mL) on days 1 and 2 of serum analysis and a CV of 5.3% (range 0-0.3 microg/mL) of RBC concentrations. Total serum AUC lithium and RBC AUC values significantly increased by 24% (p < 0.02) and by 27% (p < 0.05) with the ketorolac coadministration, respectively. An increased incidence and severity of lithium-associated side effects were reported during concomitant administration. A clinically significant drug interaction can occur when ketorolac is added to lithium therapy.