The effect of flurbiprofen on steady-state plasma lithium levels.

STUDY OBJECTIVE

To evaluate the effects of flurbiprofen therapy on the pharmacokinetics of lithium.

DESIGN

Placebo-controlled, single-blind, crossover study.

SETTING

University-affiliated hospital.

PATIENTS

Eleven healthy women with bipolar disorder.

INTERVENTIONS

The subjects received therapeutic doses of lithium administered as an immediate-release capsule every 12 hours. In addition, they received one placebo tablet every 12 hours during phase I and flurbiprofen 100 mg every 12 hours during phase II of the study.

MEASUREMENTS AND MAIN RESULTS

Steady-state pharmacokinetic parameters were measured for each phase. Lithium trough plasma concentration (Cmin) and area under the curve were statistically significantly increased (p < 0.05) when patients received flurbiprofen. Flurbiprofen also caused decreases in lithium clearance and 24-hour lithium urine excretion, although the changes did not reach statistical significance. Clinically significant increases in Cmin appeared to be associated with a greater than 1000-microgram/24 hour decrease in urinary excretion of prostaglandin E2.

CONCLUSION

Patients with clinically normal renal function may experience an increase in lithium levels with the initiation of flurbiprofen therapy.