TENIDAP SODIUM DECREASES RENAL CLEARANCE AND INCREASES STEADY-STATE CONCENTRATIONS OF LITHIUM IN HEALTHY-VOLUNTEERS

1 An open-label, randomised placebo-controlled study was conducted to determine the effects of tenidap sodium, a novel, cytokine-modulating anti-rheumatic drug, on the steady-state concentrations and renal clearance of lithium carbonate. 2 Eighteen healthy male volunteers received 450 mg lithium carbonate twice daily for 15 days and once on day 16. On days 9-16 subjects also received either placebo or 120 mg day(-1) tenidap 2 h prior to the morning dose of lithium. 3 Following a single dose of tenidap, the renal clearance of lithium decreased significantly by 0.36 1 h(-1) (-23%) compared with the clearance in the placebo group, which increased by 0.18 1 h(-1) (+14%). Steady-state serum lithium levels increased after a single dose of tenidap by 0.069 mEq 1(-1) (+13%), and in the placebo group levels increased by 0.003 mEq 1(-1) (+0.5%); this difference was not significant. 4 After 7 days' continuous administration of tenidap, the renal clearance of lithium had decreased by 0.38 1 h(-1) (-25%), compared with the placebo group in which clearance had increased by 0.16 1 h(-1) (+12%), The steady-state serum concentration of lithium increased by 0.208 mEq 1(-1) (+39%) in the tenidap group and by 0.063 mEq 1(-1) (+10%) in the placebo group, Both of these differences were significant. 5 Two subjects who received lithium plus tenidap experienced gastrointestinal side effects, compared with none of those who were administered lithium plus placebo. 6 It is recommended that serum lithium levels be monitored when tenidap and lithium are administered concomitantly.