Five chronic hemodialysis patients (1 woman and 4 men, aged, 46–68 yr) were given an oral dose of 10 mg felodipine followed by 0.057 mg [ 3 H ] felodipine IV. After 5 hours, a hemodialysis treatment lasting 4 hours was performed. Blood and dialysate flows were 200 mL/min and 500 mL/min, respectively. Capillary dialyzers with 1.3 m 2 cellulose acetate membrane were used. The pharmacokinetic characteristics and reduction in diastolic BP were similar to those in hypertensive patients with normal renal function and in uremic patients who were not treated with dialysis. There was no measurable removal of felodipine by hemodialysis. Dialyzer clearance of radioactive metabolites was about 10 mL/min, and only 8.9% of the dose was eliminated by the treatment. The half‐life of radioactive metabolites was 10 days (6–14 days) in three patients dialyzed thrice weekly. Since the metabolites are biologically inactive, no adjustment of dose is required in hemodialysis patients .
Background. The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene determines the concentration of ACE in serum and local tissues. The role of this polymorphism in progressive chronic renal disease is still not fully clear.
Four patients reacting with acute renal failure despite using low osmolar contrast media are reported. They all had diabetic nephropathy and renal insufficiency. A retrospective study of 75 consecutive patients examined with angiography showed that 13% had both of these two risk factors.
In a prospective pilot study 70 patients (age > 65 years) who underwent hip arthroplasty were treated with dicloxacillin, a total of 6 g given pre-, per- and postoperatively as antibiotic prophylaxis. Creatinine in serum and β2-microglobulin in serum and urine were determined as estimates of renal function. Values were obtained preoperatively and on days 2, 4 and 10 after operation.A slight but significant increase of serum creatinine was seen on day 2 with a gradual decrease almost down to the preoperative baseline value on day 10. Serum β2-microglobulin increased more gradually; the increase was significant on day 10. Raised levels of β2-microglobulin in urine were most pronounced: a 20-fold increase on day 2, then a slow decrease, still significant increase on day 10. This may indicate a reversible damage of proximal tubules with blocked tubular reabsorption of β2-microglobulin. The sligtly increased levels of serum creatinine and β2-microglobulin would also indicate a minor reversible decrease in glomerular filtration rate. Whether these effects are caused by the operation trauma per se or by the dicloxacillin prophylaxis cannot be determined from this pilot study. It seems quite clear that hip arthroplasty with short term prophylaxis with dicloxacillin does not result in clinically important changes in renal function.
Pharmacokinetics of [14C]omeprazole and its metabolites were studied after single intravenous and oral doses of 20 and 40 mg, respectively, to 12 patients with chronic renal insufficiency. Blood samples for determination of total radioactivity, omeprazole, OH-omeprazole, sulfone, and sulfide were taken for 24 hours. Urine was collected over 96 hours for determination of total radioactivity and during the first 24 hours for additional assay of omeprazole and metabolites. The mean systemic availability was 70%. The mean plasma t1/2 of omeprazole was 0.6 hours. Unchanged omeprazole was not measurable in urine. Derived pharmacokinetic constants of intact omeprazole were within the range of those reported in healthy individuals. The accumulated 24-hour excretion of radioactive metabolites was related significantly to creatinine clearance. The cumulative excretion of total radioactivity in urine over 96 hours in percent of given dose varied between 25% and 83%.
To test the accuracy of urea kinetic modeling (UKM), the classic fixed-volume model UKMf, two variable-volume models (UKMvb and UKMvd), direct dialysis quantification (DDQ) and a partial dialysate collection method (PDC) were evaluated in 15 stable, high-hematocrit patients. Urea generation rate (G) was also determined from a 1-week collection of total dialysate and urine (OWC). The results, except distribution volumes, were highly correlated. However, Kt/V, the normalized whole-body urea clearance, was about 8% higher with UKMvb and UKMvd. Two of three simple equations for Kt/V rendered grossly deviating, but highly correlating, results. The normalized protein catabolic rate was 8% higher with UKMvd. With OWC as reference, UKMvb and UKMvd overestimated G by 19 and 15%, respectively. All results of PDC closely followed those of DDQ. This method may be an alternative for exact quantification. Before using a new UKM method it should be compared to an established reference method.
The acetylator phenotype of 35 healthy, drug-free volunteers and 21 patients with cardiac and/or renal disease has been assessed using oral sulphapyridine. Comparative evaluation of a simplified and a more selective method of sulphapyridine analysis was performed. Thirteen of the patients were also phenotyped by determination of plasma isoniazid half-life. 81% of the patients were slow acetylators, compared with only 51% of the volunteers. When phenotyping healthy, drug-free subjects the analytical procedure, involving a direct estimation of sulphapyridine in urine with the Bratton-Marshall procedure, was satisfactory. On the other hand, in patients receiving concomitant drug therapy the more selective analytical procedure was necessary in order to diminish the risk of methodological interference.
ABSTRACT Fifteen patients with spontaneous systemic lupus erythematosus (SLE) have been phenotyped by determination of plasma isoniazid (INH) half‐life. Seven patients had signs of renal insufficiency. Of the 15 patients, 13 were slow and only 2 rapid acetylators. No correlation was found between the plasma INH half‐lives and the renal function. Thus, there is the same marked predominance of slow acetylators in patients with spontaneous SLE as in patients with the drug‐induced SLE‐like syndrome.
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