THE EFFECTS OF (L)-2-OXOTHIAZOLIDINE-4-CARBOXYLATE ON URINARY OXALATEEXCRETION

Purpose: A phase I study was done to evaluate the safety and pharmacok inetics of (L)-2-oxothiazolidine-4-carboxylate (OTZ). An ancillary obj ective was to comp are the effects of treatment with 2 levels of OTZ t o placebo on urinary oxalate excretion in healthy male subjects. Mater ials and Methods: Individuals underwent intravenous infusion of 70 (6) or 100 (6) mg./kg. body weight OTZ, or placebo for 2 hours at 4, 8-ho ur intervals. Urine was collected during the 12 hours before treatment , and at 0 to 4, 4 to 8, 8 to 24, 24 to 28, 28 to 32 and 32 to 48 hour s after the initial infusion. Urine samples were assayed for creatinin e, oxalate, citrate, sulfate, urate, phosphate and pH. Results: Urinar y oxalate excretion relative to creatinine decreased significantly in the 100 mg./kg. dose group by 4.1 mg./gm. during the first 24 hours an d by 4.6 mg./gm. in 24 to 48 hours compared to baseline values (p < 0. 05). Slight decreases of 0.9 and 1.1 mg./gm., respectively, in the 70 mg./kg. dose group, and 1.6 and 2.3 mg./gm., respectively, in the plac ebo group were observed. Oxalate excretion on day 2 in the 100 mg./kg. dose group was significantly less than that in the placebo group (p = 0.04). Urinary pH decreased and sulfate excretion increased with OTZ therapy. Conclusions: Treatment with 100 mg./kg. OTZ every 8 hours dec reases urinary oxalate excretion in healthy men.