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The effect of flurbiprofen on steady-state plasma lithium levels
B M Hughes1, R E Small, D Brink
1School of Pharmacy, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298-0533, USA.
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.