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 clea rance of lithium carbonate. 2 Eighteen healthy male volunteers receive d 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 significant ly by 0.36 1 h(-1) (-23%) compared with the clearance in the placebo g roup, which increased by 0.18 1 h(-1) (+14%). Steady-state serum lithi um 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' continuou s administration of tenidap, the renal clearance of lithium had decrea sed by 0.38 1 h(-1) (-25%), compared with the placebo group in which c learance 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 te nidap group and by 0.063 mEq 1(-1) (+10%) in the placebo group, Both o f these differences were significant. 5 Two subjects who received lith ium plus tenidap experienced gastrointestinal side effects, compared w ith none of those who were administered lithium plus placebo. 6 It is recommended that serum lithium levels be monitored when tenidap and li thium are administered concomitantly.