Tenidap sodium decreases renal clearance and increases steady-state concentrations of lithium in healthy volunteers

摘要

>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 l h^-1 (-23%) compared with the clearance in the placebo group, which increased by 0.18 l h^-1 (+14%). Steady-state serum lithium levels increased after a single dose of tenidap by 0.069 mEq l^-1 (+13%), and in the placebo group levels increased by 0.003 mEq l^-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 l h^-1 (-25%), compared with the placebo group in which clearance had increased by 0.16 l h^-1 (+12%). The steady-state serum concentration of lithium increased by 0.208 mEq l^-1 (+39%) in the tenidap group and by 0.063 mEq l^-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.