Sulindac kinetics and effects on renal function and prostaglandin excretion in renal insufficiency.
The purpose of this study was to evaluate the pharmacokinetics of sulindac, a purported "renal sparing" nonsteroidal anti-inflammatory drug, and its effects on renal function and prostaglandin excretion in patients with reduced glomerular filtration rate. Twelve female patients (glomerular filtration rate 37 +/- 4 mL/min) were treated with sulindac 200 mg bid for 11 days. Urinary PGE2, 6-keto-PGF1 alpha and serum thromboxane (TxB2) generation were measured by radioimmunoassay (RIA) following extraction on C-18 columns. Glomerular filtration rate and effective renal plasma flow were measured by 99TC-DPTA and 131I-para-aminohippuric acid clearance. In six patients serum and urine levels of sulindac and its metabolites were measured by high-pressure liquid chromatography (HPLC). Sulindac was rapidly absorbed and converted to sulindac sulfide with peak levels 2 hours after a single dose, but steady state levels were not reached prior to drug discontinuation. Sulindac sulfide AUC (0-5 hours micrograms min/mL) progressively increased from 382 to 3,030 on day 11. It did not appear in the urine. Baseline urinary PGE2 and 6-keto-PGF1 alpha excretion were 23.8 +/- 5.6 and 18.9 +/- 2.7 ng/hr respectively and were reduced by 68% and 47% by day 4 of therapy. TxB2 generation fell by 34% after one dose and by 67% by day 11. There was a significant increase in serum creatinine from 1.88 +/- 0.13 mg/dl before treatment to 2.16 +/- 0.15 mg/dL (P less than .05) after eleven days.(ABSTRACT TRUNCATED AT 250 WORDS)
Klassen
D K
DK
Johns Hopkins University School of Medicine, Department of Medicine, Baltimore, Maryland.
Stout
R L
RL
Spilman
P S
PS
Whelton
A
A
D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000503:physiopathology*; D007677:Kidney Function Tests; D011453:Prostaglandins / Q000652:urine*; D013467:Sulindac / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D013931:Thromboxanes / Q000097:blood
D011453:Prostaglandins; D013931:Thromboxanes; D013467:Sulindac