Acute clinical tolerance of creatinol O-phosphate.

Acute clinical tolerance to N-methyl-N-(beta-hydroxyethyl) guanidine O-phosphate (creatinol O-phosphate, COP) was investigated in volunteer human subjects without heart or renal disease and without other serious illness. COP was administered i.v. at three different dosages, 1020 mg (group A), 2040 mg (group B) and 3060 mg (group C), in comparison with a placebo (group D). Arterial pressure, heart rate, ECG pattern and a complete blood analysis showed no change at any COP dosage, with the exception of blood phosphate, which increased in groups B and C. Cumulative urinary excretion of phosphate and creatinine and diuresis increased, whereas other urine parameters did not change. The phosphate and creatinine increases derived from the COP molecule and the increase in diuresis from a simple osmotic process required to dilute the phosphate in the tubular fluid. All these alterations were statistically significant and dose-related with COP and had been expected. COP proved to be a very well tolerated drug without any evident side effect.