[Pharmacokinetics and clinical effect of recombinant human erythropoietin on the anemia of predialysis patients].

The marvelous effect of recombinant human erythropoietin (EPOCH) on the anemia of the patients suffering from chronic renal failure had been already reported even in the predialysis patients. However, the influence on residual renal function as well as pharmacokinetics of EPOCH in predialysis patients was not clarified yet. Therefore, we made a clinical study of EPOCH in 10 predialysis patients to investigate the clinical effect as well as pharmacokinetics. EPOCH was administered intravenously once a week with the dosage of 3,000-9,000 IU for 8 weeks. All patients showed prominent improvement of anemia. Though no patient show serious adverse effect, two patients showed controllable hypertension accompanying with the increase of hematocrit. Meanwhile, the speed of the deterioration of residual renal function obtained from the regression line by reciprocal of the serum creatinine was not aggravated by the correction of anemia. Pharmacokinetic study revealed that the halflife of EPOCH was extended compared to normal but the degree of extension was same as that of in dialyzed patients. The plasma concentration-time curves showed the pattern of monoexponential disappearance and the area under the curve (AUC 0 to 48 hr.) showed dose-response increase. However, both parameters mentioned above as well as systemic clearance rate did not show any change between those of on day 0 and on day 56. These results no long-term accumulation of EPOCH, though the level of intrinsic erythropoietin was decreased after EPOCH treatment. Thus, the beneficial effect of EPOCH on the correction of anemia was revealed even in the predialysis patients without affecting on residual renal function.