PMID- 11599659
OWN - NLM
STAT- MEDLINE
DCOM- 20020410
LR  - 20190813
IS  - 0031-6970 (Print)
IS  - 0031-6970 (Linking)
VI  - 57
IP  - 5
DP  - 2001 Aug
TI  - Pharmacokinetics and pharmacodynamics of epoetin alfa once weekly and three times 
      weekly.
PG  - 411-8
AB  - OBJECTIVE: To compare the pharmacokinetics, pharmacodynamics, and tolerance of 
      epoetin alfa administered subcutaneously (s.c.) once weekly (q.w.) and three 
      times weekly (t.i.w.). METHODS: An open-label, randomized, parallel-design study 
      was conducted in 36 healthy adults with hemoglobin (Hb) levels of 11.7 14.0 g/dl 
      for women and 13.0-14.8 g/dl for men. Subjects were randomized to epoetin alfa 
      150 IU/kg s.c. t.i.w. or 40,000 IU s.c. q.w. for 4 weeks. Serum erythropoietin 
      concentrations were measured using a validated enzyme-linked immunosorbent assay 
      (ELISA). Pharmacokinetic parameters [peak serum concentration (Cmax), mean 
      predose trough concentration (Cmin), time to Cmax (tmax), clearance after s.c. 
      administration (CL/F), area under the plasma concentration time curve (AUC), and 
      terminal elimination half-life (t 1/2)] were calculated using model-independent 
      methods. Mean changes from baseline and AUC of percentage reticulocytes, Hb, and 
      total red blood cell (RBC) concentrations over the 1-month study period were 
      calculated. RESULTS: The Cmax values for serum epoetin alfa q.w. were six times 
      and AUC(0-168) values three times that of the t.i.w. regimen. Time profiles of 
      changes in percentage reticulocytes, Hb, and total RBC over 1 month were similar 
      between regimens. The rate of increase in Hb was similar for the two groups, and 
      both groups exhibited a 3.1-g/dl increase in mean Hb levels from baseline through 
      day 29. Changes in ferritin levels were generally similar between groups and 
      reflected expected use of iron stores for Hb production. Epoetin alfa 
      administered t.i.w. or q.w. was well tolerated and no serious adverse events 
      occurred. CONCLUSION: The pharmacodynamic responses were equivalent between 
      groups despite expected differences in total erythropoietin exposure. These 
      results indicate that the epoetin alfa 150 IU/kg t.i.w. and 40,000 IU q.w. 
      regimens can be considered clinically equivalent.
FAU - Cheung, W
AU  - Cheung W
AD  - The R W Johnson Pharmaceutical Research Institute, Raritan, NJ 08869, USA.
FAU - Minton, N
AU  - Minton N
FAU - Gunawardena, K
AU  - Gunawardena K
LA  - eng
PT  - Clinical Trial
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - Germany
TA  - Eur J Clin Pharmacol
JT  - European journal of clinical pharmacology
JID - 1256165
RN  - 0 (Hematinics)
RN  - 0 (Hemoglobins)
RN  - 0 (Recombinant Proteins)
RN  - 11096-26-7 (Erythropoietin)
RN  - 64FS3BFH5W (Epoetin Alfa)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Anemia/prevention & control
MH  - Area Under Curve
MH  - Biological Availability
MH  - Drug Administration Schedule
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Epoetin Alfa
MH  - Erythrocyte Count
MH  - Erythropoietin/administration & dosage/adverse 
      effects/*pharmacokinetics/*pharmacology
MH  - Female
MH  - Half-Life
MH  - Hematinics/administration & dosage/adverse 
      effects/*pharmacokinetics/*pharmacology
MH  - Hemoglobins/metabolism
MH  - Humans
MH  - Injections, Subcutaneous
MH  - Male
MH  - Recombinant Proteins
MH  - Reticulocyte Count
EDAT- 2001/10/16 10:00
MHDA- 2002/04/11 10:01
CRDT- 2001/10/16 10:00
PHST- 2001/10/16 10:00 [pubmed]
PHST- 2002/04/11 10:01 [medline]
PHST- 2001/10/16 10:00 [entrez]
AID - 10.1007/s002280100324 [doi]
PST - ppublish
SO  - Eur J Clin Pharmacol. 2001 Aug;57(5):411-8. doi: 10.1007/s002280100324.