Effects of diclofenac on lithium kinetics

The influence of the prostaglandin (PG) synthesis-inhibiting, nonsteroidal anti-inflammatory drug (NSAID) diclofenac on lithium kinetics was studied in five normal women on a 150-mEq sodium diet. Diclofenac decreased lithium renal clearance by 23% (P - 0.002) and increased lithium plasma levels by 26% (P - 0.001). Renal PG synthesis was suppressed by 53% of control values. These data show a clinically important drug interaction, possibly on the basis of a PG-dependent mechanism, with the risk of lithium intoxication for patients treated with lithium salts and NSAIDs.