39328
document
Pharmacokinetics and pharmacodynamics of six epoetin alfa dosing regimens in anemic critically ill patients without acute blood loss . OBJECTIVE To describe the pharmacokinetic profiles of six different dosing regimens for epoetin alfa , and whether more rapid and robust reticulocytosis can be elicited with more frequent administration of epoetin alfa in anemic critically ill patients . DESIGN Randomized , open-label , multicenter , 28-day clinical trial . SETTING Ten centers in the United States . PATIENTS Adult ( age > or=18 years ) critically ill patients with hemoglobin < or=12 g/dL , expected hospitalization of > or=7 days , with no ongoing acute blood loss . INTERVENTIONS One of six dosing epoetin alfa regimens for 15 days , as follows : 40,000 IU once weekly , subcutaneously ( group A ) or intravenously ( IV ) ( group B ) ; 15,000 IU every other day , subcutaneously ( group C ) or IV ( group D ) ; or 40,000 IU day 1 and 3 , subcutaneously ( group E ) or IV ( group F ) , followed by 15,000 IU once every other day on [ corrected ] days 5-15 [ corrected ] MEASUREMENTS Serum erythropoietin concentration , absolute reticulocyte count , and adverse events . MAIN RESULTS Of the 60 patients who were enrolled ( 60 % men , mean age 53 years , mean Acute Physiology and Chronic Health Evaluation II score , 19.5 ) , 30 were evaluable for both pharmacokinetics and pharmacodynamics ( 50 % ) . Erythropoietin exposure was approximately ten times greater for IV dosing than for subcutaneous dosing . Mean absolute reticulocyte count peaked at day 11 or 15 in each group and appeared to be greater for subcutaneous dosing ( mean peak response 149-169 x 10 ( 9 ) /L ) compared with IV dosing ( mean peak response 138-147 x 10 ( 9 ) /L ) at most visits . The most frequently reported adverse events were pyrexia ( 18 % ) , hypokalemia ( 15 % ) , and hypophosphatemia ( 15 % ) . CONCLUSIONS In this study of anemic critically ill patients treated with epoetin alfa , all dosing regimens were well tolerated and appeared to effect reticulocytosis , with a peak at day 11 or 15 in most patients . The pharmacokinetics of epoetin alfa did not predict pharmacodynamic response in anemic critically ill patients .
39329
Intervention_Pharmacological
epoetin alfa
39330
Intervention_Pharmacological
epoetin alfa
39331
Intervention_Pharmacological
epoetin alfa
39332
Intervention_Pharmacological
six dosing epoetin alfa regimens
39333
Intervention_Pharmacological
40,000 IU once weekly
39334
Intervention_Pharmacological
15,000 IU every other day , subcutaneously
39335
Intervention_Pharmacological
40,000 IU day
39336
Intervention_Pharmacological
subcutaneously
39337
Intervention_Physical
Erythropoietin exposure
39338
Intervention_Pharmacological
subcutaneous dosing
39339
Intervention_Pharmacological
dosing
39340
Intervention_Pharmacological
epoetin alfa
39341
Intervention_Pharmacological
epoetin alfa
39342
Outcome_Physical
Serum erythropoietin concentration
39343
Outcome_Physical
absolute reticulocyte count
39344
Outcome_Adverse-effects
adverse events
39345
Outcome_Physical
Erythropoietin exposure
39346
Outcome_Physical
Mean absolute reticulocyte count
39347
Outcome_Adverse-effects
adverse events
39348
Outcome_Adverse-effects
pyrexia
39349
Outcome_Adverse-effects
hypokalemia
39350
Outcome_Adverse-effects
hypophosphatemia
39351
Outcome_Physical
reticulocytosis
39352
Outcome_Physical
pharmacodynamic response