B M Hughes1, R E Small, D Brink, N D McKenzie. 1. School of Pharmacy, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298-0533, USA.
Abstract
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.
RCT Entities:
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.
Authors: Richard T Scheife; Lisa E Hines; Richard D Boyce; Sophie P Chung; Jeremiah D Momper; Christine D Sommer; Darrell R Abernethy; John R Horn; Stephen J Sklar; Samantha K Wong; Gretchen Jones; Mary L Brown; Amy J Grizzle; Susan Comes; Tricia Lee Wilkins; Clarissa Borst; Michael A Wittie; Daniel C Malone Journal: Drug Saf Date: 2015-02 Impact factor: 5.606