The family of an unusual subject was studied. When tested with chlorzoxazone (CX; 250 mg p.o.) on four separate occasions 5 years ago, this subject showed abnormally slow renal elimination of 6-hydroxychlorzoxazone (HCX), the primary CX metabolite. Since rates of CX biotransformation to HCX have served as a probe of the important cytochrome P450 isozyme, CYP 2E1, it was of interest that this unusual subject had normal conversion of CX to HCX. The present study revealed that over the past 5 years this subject accelerated his renal rate of HCX elimination which now lies at the slow end of the curve for normal subjects. His wife and 5 children all had more rapid rates than he for renal HCX elimination.
Cardiovascular disease is the leading cause of mortality in end-stage renal disease (ESRD) patients receiving dialysis. In these patients, hypertriglyceridemia appears to increase the risk of accelerated atherosclerosis. The present placebo-controlled study evaluated prospectively lipid-lowering effects of pyrazinoylguanidine (PZG) in 6 ESRD patients undergoing maintenance hemodialysis. The design of the study entailed a placebo phase of 1 week followed by 3 weeks of PZG, 400 mg three times a day. Compared to placebo, PZG reduced serum triglycerides (PZG vs. placebo 370 ± 171 vs. 414 ± 182 mg/dl; p = 0.01). PZG also tended to decrease total cholesterol. In addition, PZG selectively lowered blood glucose in hyperglycemic patients. PZG was well tolerated; it did not interfere with hemodynamic parameters or alter liver function tests, nutritional parameters or dialysis clearance.
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