Pharmacokinetics of etoricoxib in patients with renal impairment.

The effect of renal insufficiency on the pharmacokinetics of etoricoxib, a selective inhibitor of cyclooxygenase-2, was examined in 23 patients with varying degrees of renal impairment (12 moderate [creatinine clearance between 30 and 50 mL/min/1.73 m2], 5 severe [creatinine clearance below 30 mL/min/1.73 m2], and 6 with end-stage renal disease requiring hemodialysis) following administration of single 120-mg oral doses of etoricoxib. Even the most severe renal impairment was found to have little effect on etoricoxib pharmacokinetics. The low recovery of etoricoxib in dialysate (less than 6% of the dose) supports that hemodialysis also has little effect on etoricoxib pharmacokinetics, and binding of etoricoxib to plasma proteins was generally unaffected by renal disease. Single doses of etoricoxib were generally well tolerated by patients with renal impairment. Based on pharmacokinetic considerations, dosing adjustments are not necessary for patients with any degree of renal impairment. However, because patients with advanced renal disease (creatinine clearance below 30 mL/min/1.73 m2) are likely to be very sensitive to any further compromise of renal function, and there is no long-term clinical experience in these patients, the use of etoricoxib is not recommended in patients with advanced renal disease.

Betaine supplementation decreases post-methionine hyperhomocysteinemia in chronic renal failure.

BACKGROUND: Fasting and post-methionine load hyperhomocysteinemia are independent risk factors for vascular disease that are common in chronic renal failure. Folate decreases but seldom normalizes fasting total homocysteine (tHcy) concentrations in such patients. Glycine betaine (GB) is known to decrease tHcy in other clinical settings, but whether it is beneficial in chronic renal failure has not been established. METHODS: We conducted a crossover-controlled trial in 36 patients with chronic renal failure to determine if oral GB decreased fasting or post-methionine tHcy concentrations. All subjects received, in randomized sequence, 5-mg folic acid and 50-mg pyridoxine daily, with or without GB 4-g daily, for three months each. Fasting plasma tHcy, GB, folate, B vitamins, serum lipids and creatinine were measured at one and three months, and methionine load tests were performed at the end of each three-month treatment phase. RESULTS: GB and N,N-dimethylglycine (DMG) levels in plasma and urine increased markedly during GB treatment. Fasting tHcy decreased from baseline with both treatments but did not differ between treatments. Post-methionine tHcy decreased with both treatments and was 18% lower on GB than on folate and pyridoxine alone (P < 0.001). There were small increases in lipids during treatment with GB but the ratio of total: HDL cholesterol was unchanged. CONCLUSIONS: GB supplementation had no effect on fasting tHcy in patients with chronic renal failure who were folate and pyridoxine replete, but it significantly decreased tHcy concentrations after methionine loading.