A 1500 mg dose of salsalate (SSA) was given to five patients undergoing chronic hemodialysis on an interdialytic day and again before dialysis. Compared with ...
Salsalate kinetics in patients with chronic renal failure undergoing hemodialysis A 1500 mg dose of salsalate (SSA) was given to five patients undergoing chronic hemodialysis on an interdialytic day and again before dialysis. Compared with control subjects, patients undergoing dialysis had a lower peak plasma SSA level (17 ± 3 vs. 45 ± 2 pg/m1; P < 0.01) that occurred slightly later. In contrast, plasma salicylic acid (SA), the active SSA metabolite, had a similar but later peak level that remained substantially higher. Therefore, the AUC for SA was increased by 50% and the SA ti,, was prolonged in the patients receiving dialysis (8.1 ± 0.7 vs. 3.8 ± 0.2 hours; P < 0.01). During a single treatment, dialysis clearance reduced plasma SA levels, removed 18% of total body SA, and returned the SA ti,, to nearly normal. Because the elimination of SA is impaired in patients undergoing dialysis, the interdialytic SSA dosage should be reduced. Hemodialysis improves SA kinetics and may be followed by a normal SSA replacement dose. However, periodic monitoring of plasma SA levels is reconunended when SSA dosing is begun in patients receiving dialysis. (GUN PHARmAcoL THER 1986;39:420-4.)
Mark E. Williams, M.D., Michael Weinblatt, M.D., Robert M. Rosa, M.D., Victoria L. Griffin, R.N., B.S., M. Barry Goldlust, Ph.D., Shaw F. Shang, M.S., Lester I. Harrison, Ph.D., and Robert S. Brown, M.D. Boston, Mass., and Northridge, Salsalate (SSA) is a nonacetylated salicylate member of the nonsteroidal group of anti-inflammatory drugs (NSAIDs). SSA is similar to aspirin in its therapeutic effectiveness for arthritic disorders,' but causes no platelet dysfunction' and produces less gastrointestinal bleeding and gastric erosions than do NSAIDs such as aspirin.' Patients with uremia have a high incidence of gastric mucosal erosions and hemorrhagic gastritis:5'7 Disorders of platelet function, which are also consistently found in uremia,' may contribute to alimentary bleeding and ecchymoses as well as to bleeding from the gums and vagina. However, these patients frequently require the use of salicylates or other NSAIDs for a variety of rheumatic syndromes.' Little is known about SSA kinetics in patients with renal failure undergoing chronic hemodialysis, and previous reports have presented conflicting data on the From the Charles A. Dana Research Institute and the Thorndike Laboratory, Department of Medicine, Harvard Medical School and Beth Israel Hospital, Boston, and the Departments of Clinical Research and Drug Metabolism, Riker Laboratories, Northridge. Supported in part by a grant from Riker Laboratories and from Grant No. MO1 RR 01032 of the General Clinical Research Center, Division of Research Resources, National Institutes of Health. Received for publication Sept. 18, 1985; accepted Nov. 22, 1985. Reprint requests to: Dr. Mark E. Williams, Department of Medicine, Beth Israel Hospital, 330 Brookline Ave., Boston, MA 02215.
420
Calif.
renal contribution to the elimination of salicylic acid (SA),'°" the active SSA metabolite. Our present study was undertaken to evaluate the kinetics of SSA and SA in patients with chronic renal failure undergoing a single hemodialysis treatment, to determine whether impaired renal excretion or hemodialytic clearance would require a change in the SSA dosing regimen.
METHODS Five patients undergoing chronic hemodialysis (three women and two men) between 36 and 80 years old who had no medical conditions known to interfere with drug absorption or biotransformation entered and completed the study (Table I). All patients had endogenous creatinine clearances
