Bumex, same short pharmacokinetics of lasix with better bioavailability

I'm working more at Providence Hospital and I find that the intensivists and cardiologists love the Bumex. This opinion is shared by some prominant nephrologists. Unfortunately bumetanide suffers from the same short pharmacokinetics as furosemide: half life of about 90 minutes after oral or IV dosing. The big advantage bumetanide has over furosemide is more predictable bioavailability after oral dosing. Torsemide trumps both of them with excellent bioavailablity and a half-life of 210 minutes.

The reason that bumex is preferred is the beleif that it is a more potent diuretic than furosemide. According to Brater, all of the loop diuretics have similar potency and decisions among the loops should be based on pharmaokinetics (as opposed to pharmacodynamics). Here is the statement in his NEJM review of diuretic therapy.


Phamacokinetics of torsemide, bumetanide and furosemide from the package inserts. And here is the table from Brater's reveiw:

When does the melamine story progress from the tragic to the absurd. Gorillas?

The latest victims of the melamine incident: gorillas.

Melamine Crisis: "There is no problem"

"There is no problem," Xiang Yuzhang, the national quality watchdog's chief inspection official, told reporters in Beijing.

Love the close of this article with a quote by the Chinese equivalent of Baghdad Bob.

This on the same day that 5 cases of kidney stones in children surfaced in Taiwan.

Journal Club: Aspirin and FGF-23

The first article was an intriguing look at various renal function parameters and how they respond to various doses of aspirin. All the patients were pre-treated with enalepril and a thiazide diuretic for 6 days. Then they were given one of four doses of aspirin:

1. placebo
2. 80 mg
3. 160 mg
4. 320 mg

They found decreased GFR, decreased sodium clearance, decreased solute clearance and decreased free water clearance with 160 mg and 320 mg but the effect was transient with all factors returning to baseline 4 hours after the aspirin was administered.

The article has a long introduction and discussion outlining all of the heart failure studies which have shown that aspirin can be harmful or can decrease the effectiveness of ACEi in heart failure.

The study is small (n=16, with each participant randomized to two doses of aspirin with a 2 week washout between doses) and the authors fail to fully describe the cohort. The primary weakness is the authors want to extrapolate there findings over 6 hours to the effect of aspirin taken chronically for years. Additionally they make the leap of using aspirin-induced changes in renal function to be a proxy for interference with ACEi effect on heart failure survival.

Nonetheless it will change the way I practice. I had previously given my patients (who essentially all are on diuretics and ACEi) the green light to take aspirin any way they want. I will now suggest they limit themselves to 81 mg for CAD protection.

The second article was the NEJM article on FGF-23 and the risk of mortality in hemodialysis patients. FGF-23, or fibroblast growth factor-23, is a newly discovered molecule which regulates the phosphorous in the body. It is one of the primary phosphatonins, signals which increase the renal excretion of phosphorous. Additionally they suppress 1-alpha hydroxylase lowering the amount of 1,25 dihydroxy-vitamin D.

This is prospective cohort with nested case-control of incident dialysis patients in the U.S. The investigators looked at 200 patients who died (cases) in the first year and compared them to 200 patients who survived one year (control). FGF-23 was measured on the first day of dialysis. They divided the cohort into quartiles based on phosphorous and found that patients who subsequently died had increased FGF-23. They found a graded increase in the risk of death with increased FGF-23 level that was signifigant in the whole cohort and inevery quartile of phosphorous except the highest.They also showed a dose responce of mortality to FGF-23 levels in the whole cohort in the crude data, case-mix adjusted and multivariate adjusted.


The authors in the discussion point out that the association of FGF-23 with mortality is stronger than that found with phosphorous and mortality. They found FGF-23 levels were 22% lower in African-Americans than in Caucasians. The authors leave a tease that this lower level of FGF-23 level may explain the improved survival found in African Americans on dialysis.