Pharmacokinetics and pharmacodynamics of pegfilgrastim

Clinical Pharmacokinetics

Volumn 50, Issue 5, 2011, Pages 295-306

  Yang, Bing Bing ^a   Kido, Anna ^a  

^a AMGEN INC   (United States)

Author keywords

Febrile neutropenia; Granulocyte colony stimulating factors, pharmacodynamics; Granulocyte colony stimulating factors, pharmacokinetics; Neutropenia; Pegfilgrastim, pharmacodynamics; Pegfilgrastim, pharmacokinetics; Pharmacokinetic pharmacodynamic relationships

Indexed keywords

BLEOMYCIN; CARBOPLATIN; CYCLOPHOSPHAMIDE; DOCETAXEL; DOXORUBICIN; ETOPOSIDE; GRANULOCYTE COLONY STIMULATING FACTOR; HEMOPOIETIC GROWTH FACTOR; PACLITAXEL; PREDNISONE; PROCARBAZINE; RECOMBINANT GRANULOCYTE COLONY STIMULATING FACTOR; RITUXIMAB; VINCRISTINE; VINCRISTINE SULFATE;

ACUTE GRANULOCYTIC LEUKEMIA; AREA UNDER THE CURVE; B CELL LYMPHOMA; BONE PAIN; BREAST CANCER; CANCER CHEMOTHERAPY; CANCER COMBINATION CHEMOTHERAPY; CELL SURFACE; DOSE RESPONSE; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG EFFICACY; DRUG ELIMINATION; DRUG MECHANISM; DRUG SAFETY; ENDOCYTOSIS; HOMEOSTASIS; HUMAN; KIDNEY CLEARANCE; LUNG NON SMALL CELL CANCER; LUNG SMALL CELL CANCER; LYMPHOMA; MAXIMUM PLASMA CONCENTRATION; MULTIPLE CYCLE TREATMENT; NEUTROPENIA; NEUTROPHIL; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; REVIEW;

ANIMALS; ANTINEOPLASTIC AGENTS; DRUG DOSAGE CALCULATIONS; DRUG INTERACTIONS; FILGRASTIM; HUMANS; MODELS, BIOLOGICAL; NEUTROPENIA; NEUTROPHILS;

EID: 79953303640     PISSN: 03125963     EISSN: 11791926     Source Type: Journal    
DOI: 10.2165/11586040-000000000-00000     Document Type: Review

References (77)

1. Dale D. Current management of chemotherapy-induced neutropenia: the role of colony-stimulating factors. Semin Oncol 2003 Aug; 30 (4 Suppl. 13): 3-9. (Pubitemid 37140185)
2. Demetri GD, Griffin JD. Granulocyte colony-stimulating factor and its receptor. Blood 1991 Dec 1; 78 (11): 2791-808.
3. Welte K, Gabrilove J, Bronchud MH, et al. Filgrastim (r-metHuG-CSF): the first 10 years. Blood 1996 Sep 15; 88 (6): 1907-29. (Pubitemid 26307891)
4. Neupogen- (filgrastim): US prescribing information. Thousand Oaks (CA): Amgen Inc., 2010 Mar [online]. Available from URL: http://www.neupogen. com/pdf/Neupogen-PI.pdf [Accessed 2011 Jan 19].
5. Kuwabara T, Kobayashi S, Sugiyama Y. Pharmacokinetics and pharmacodynamics of a recombinant human granulocyte colony-stimulating factor. Drug Metab Rev 1996 Nov; 28 (4): 625-58. (Pubitemid 26417564)
6. Roskos LK, Cheung E, Vincent M, et al. Pharmacokinetics and pharmacodynamics of a recombinant human granulocyte colony-stimulating factor. In: Morstyn G, Dexter M, editors. Filgrastim (r-metHuG-CSF) in clinical practice. 2nd ed. New York: Marcel Dekker, Inc., 1998: 51-71.
7. Metcalf D. Hematopoietic cytokines. Blood 2008 Jan 15; 111 (2): 485-91.
8. Bartocci A, Mastrogiannis DS, Migliorati G, et al. Macrophages specifically regulate the concentration of their own growth factor in the circulation. Proc Natl Acad Sci USA 1987 Sep; 84 (17): 6179-83.
9. Bukowski RM, Budd GT, Gibbons JA, et al. Phase I trial of subcutaneous recombinant macrophage colony-stimulating factor: clinical and immunomodulatory effects. J Clin Oncol 1994 Jan; 12 (1): 97-106.
10. Kato M, Kamiyama H, Okazaki A, et al. Mechanism for the nonlinear pharmacokinetics of erythropoietin in rats. J Pharmacol Exp Ther 1997 Nov; 283 (2): 520-7. (Pubitemid 27514606)
11. Jelkmann W. The enigma of the metabolic fate of circulating erythropoietin (Epo) in view of the pharmacokinetics of the recombinant drugs rhEpo and NESP. Eur J Haematol 2002 Nov-Dec; 69 (5-6): 265-74. (Pubitemid 36005815)
12. Gross AW, Lodish HF. Cellular trafficking and degradation of erythropoietin and novel erythropoiesis stimulating protein (NESP). J Biol Chem 2006 Jan 27; 281 (4): 2024-32. (Pubitemid 43845790)
13. Nichol JL. TheMpl ligand and platelet homeostasis. Acta Paediatr Suppl. 1998 Jun; 424: 7-15.
14. Scheding S, BergmannM, Shimosaka A, et al. Human plasma thrombopoietin levels are regulated by binding to platelet thrombopoietin receptors in vivo. Transfusion 2002 Mar; 42 (3): 321-7.
15. Petros WP, Rabinowitz J, Stuart AR, et al. Disposition of recombinant human granulocyte-macrophage colony-stimulating factor in patients receiving high-dose chemotherapy and autologous bone marrow support. Blood 1992 Sep 1; 80 (5): 1135-40.
16. Layton JE, Hockman H, Sheridan WP, et al. Evidence for a novel in vivo control mechanism of granulopoiesis: mature cell-related control of a regulatory growth factor. Blood 1989 Sep; 74 (4): 1303-7. (Pubitemid 19227439)
17. Stute N, Santana VM, Rodman JH, et al. Pharmacokinetics of subcutaneous recombinant human granulocyte colony-stimulating factor in children. Blood 1992 Jun 1; 79 (11): 2849-54.
18. Kearns CM, Wang WC, Stute N, et al. Disposition of recombinant human granulocyte colony-stimulating factor in children with severe chronic neutropenia. J Pediatr 1993 Sep; 123 (3): 471-9. (Pubitemid 23258178)
19. TakataniH, SodaH, FukudaM, et al. Levels of recombinant human granulocyte colony-stimulating factor in serum are inversely correlated with circulating neutrophil counts. Antimicrob Agents Chemother 1996 Apr; 40 (4): 988-91.
20. Sturgill MG, Huhn RD, Drachtman RA, et al. Pharmacokinetics of intravenous recombinant human granulocyte colony-stimulating factor (rhG-CSF) in children receiving myelosuppressive cancer chemotherapy: clearance increases in relation to absolute neutrophil count with repeated dosing. Am J Hematol 1997 Feb; 54 (2): 124-30. (Pubitemid 27079418)
21. Wang YM, Krzyzanski W, Doshi S, et al. Pharmacodynamics-mediated drug disposition (PDMDD) and precursor pool lifespan model for single dose of romiplostim in healthy subjects. AAPS J 2010; 12: 729-40.
22. Panopoulos AD, Watowich SS. Granulocyte colony-stimulating factor: molecular mechanisms of action during steady state and 'emergency' hematopoiesis. Cytokine 2008 Jun; 42 (3): 277-88.
23. Kuwabara T, Uchimura T, KobayashiH, et al. Receptor-mediated clearance of G-CSF derivative nartograstim in bone marrow of rats. Am J Physiol 1995 Jul; 269 (1 Pt 1): E1-9.
24. Kuwabara T, Uchimura T, Takai K, et al. Saturable uptake of a recombinant human granulocyte colony-stimulating factor derivative, nartograstim, by the bone marrowand spleen of rats in vivo. JPharmacol ExpTher 1995 Jun; 273 (3): 1114-22.
25. Kuwabara T, Kobayashi S, SugiyamaY.Kinetic analysis of receptor-mediated endocytosis of G-CSF derivative, nartograstim, in rat bone marrow cells. Am J Physiol 1996 Jul; 271 (1 Pt 1): E73-84.
26. Terashi K, Oka M, Ohdo S, et al. Close association between clearance of recombinant human granulocyte colony-stimulating factor (G-CSF) and G-CSF receptor on neutrophils in cancer patients. Antimicrob Agents Chemother 1999 Jan; 43 (1): 21-4. (Pubitemid 29069193)
27. Khwaja A, Carver J, Jones HM, et al. Expression and dynamic modulation of the human granulocyte colony-stimulating factor receptor in immature and differentiated myeloid cells. Br J Haematol 1993 Oct; 85 (2): 254-9. (Pubitemid 23309558)
28. Piper MG, Massullo PR, Loveland M, et al. Neutrophil elastase downmodulates native G-CSFR expression and granulocyte-macrophage colony formation. J Inflamm (Lond) 2010; 7 (1): 5.
29. Tanaka H, Tokiwa T. Influence of renal and hepatic failure on the pharmacokinetics of recombinant human granulocyte colony-stimulating factor (KRN8601) in the rat. Cancer Res 1990 Oct 15; 50 (20): 6615-9. (Pubitemid 20348788)
30. Yang BB, Lum PK, Hayashi MM, et al. Polyethylene glycol modification of filgrastim results in decreased renal clearance of the protein in rats. J Pharm Sci 2004 May; 93 (5): 1367-73. (Pubitemid 38529709)
31. EmmanoualD, Lindheimer M, Katz A. Role of kidney in hormonemetabolism and its implications in clinical medicine. Klin Wochenschr 1980; 58: 1005-12.
32. Maack T, JohnsonV,Kau ST, et al. Renal filtration, transport, and metabolism of low-molecular-weight proteins: a review.Kidney Int 1979 Sep; 16 (3): 251-70. (Pubitemid 10208487)
33. Nielson JT. Handling of proteins in isolated and in vitro perfused proximal tubules from rat kidney. Danish Med Bull 1990; 37: 197-210.
34. Fukuda M, Oka M, Ishida Y, et al. Effects of renal function on pharmacokinetics of recombinant human granulocyte colony-stimulating factor in lung cancer patients. Antimicrob Agents Chemother 2001 Jul; 45 (7): 1947-51. (Pubitemid 32591681)
35. Kinstler O, Molineux G, Treuheit M, et al. Mono-N-terminal poly(ethylene glycol)-protein conjugates. Adv Drug Deliv Rev 2002 Jun 17; 54 (4): 477-85. (Pubitemid 34615544)
36. Molineux G. The design and development of pegfilgrastim (PEG-rmetHuGCSF, Neulasta). Curr Pharm Des 2004; 10 (11): 1235-44. (Pubitemid 38425903)
37. Jain A, Jain SK. PEGylation: an approach for drug delivery. A review. Crit Rev Ther Drug Carrier Syst 2008; 25 (5): 403-47.
38. Jevsevar S, Kunstelj M, Porekar VG. PEGylation of therapeutic proteins. Biotechnol J 2010 Jan; 5 (1): 113-28.
39. Harris JM, Martin NE, Modi M. Pegylation: a novel process for modifying pharmacokinetics. Clin Pharmacokinet 2001; 40 (7): 539-51. (Pubitemid 32738660)
40. Caliceti P, Veronese FM. Pharmacokinetic and biodistribution properties of poly(ethylene glycol)-protein conjugates. Adv Drug Deliv Rev 2003 Sep 26; 55 (10): 1261-77. (Pubitemid 37464561)
41. Fishburn CS. The pharmacology of PEGylation: balancing PD with PK to generate novel therapeutics. J Pharm Sci 2008 Oct; 97 (10): 4167-83.
42. Tattini Jr V, Parra DF, Polakiewicz B, et al. Effect of lyophilization on the structure and phase changes of PEGylated-bovine serum albumin. Int J Pharm 2005 Nov 4; 304 (1-2): 124-34. (Pubitemid 41427656)
43. Tomiya N, Watanabe K, Awaya J, et al. Modification of acyl-plasmin-streptokinase complex with polyethylene glycol: reduction of sensitivity to neutralizing antibody. FEBS Lett 1985 Nov 25; 193 (1): 44-8. (Pubitemid 16170822)
44. Abuchowski A, Davis FF. Preparation and properties of polyethylene glycoltrypsin adducts. Biochim Biophys Acta 1979 May 23; 578 (1): 41-6.
45. Molineux G, Kinstler O, Briddell B, et al. A new form of filgrastim with sustained duration in vivo and enhanced ability to mobilize PBPC in both mice and humans. Exp Hematol 1999 Dec; 27 (12): 1724-34.
46. Lord BI, Woolford LB, Molineux G. Kinetics of neutrophil production in normal and neutropenic animals during the response to filgrastim (r-metHu G-CSF) or filgrastim SD/01 (PEG-r-metHu G-CSF). Clin Cancer Res 2001 Jul; 7 (7): 2085-90. (Pubitemid 32994848)
47. Johnston E, Crawford J, Blackwell S, et al. Randomized, dose-escalation study of SD/01 compared with daily filgrastim in patients receiving chemotherapy. J Clin Oncol 2000 Jul; 18 (13): 2522-8. (Pubitemid 30432517)
48. Holmes FA, O'Shaughnessy JA, Vukelja S, et al. Blinded, randomized, multicenter study to evaluate single administration pegfilgrastim once per cycle versus daily filgrastim as an adjunct to chemotherapy in patients with high-risk stage II or stage III/IV breast cancer. J Clin Oncol 2002 Feb 1; 20 (3): 727-31. (Pubitemid 34111380)
49. Green MD, Koelbl H, Baselga J, et al. A randomized double-blind multicenter phase III study of fixed-dose single-administration pegfilgrastim versus daily filgrastim in patients receiving myelosuppressive chemotherapy. Ann Oncol 2003 Jan; 14 (1): 29-35. (Pubitemid 36150255)
50. Roskos LK, Lum P, Lockbaum P, et al. Pharmacokinetic/pharmacodynamic modeling of pegfilgrastim in healthy subjects. J Clin Pharmacol 2006 Jul; 46 (7): 747-57. (Pubitemid 43882798)
51. Morstyn G, Campbell L, Souza LM, et al. Effect of granulocyte colony stimulating factor on neutropenia induced by cytotoxic chemotherapy. Lancet 1988 Mar 26; 1 (8587): 667-72. (Pubitemid 18083268)
52. Data on file, Amgen Inc., 2011.
53. Yang BB. Integration of pharmacokinetics and pharmacodynamics into the drug development of pegfilgrastim, a pegylated protein. In: Meibohm B, editor. Pharmacokinetics and pharmacodynamics of biotech drugs. Weinheim: Wiley-VCH Verlag GmbH, 2006: 373-93.
54. Holmes FA, Jones SE, O'Shaughnessy J, et al. Comparable efficacy and safety profiles of once-per-cycle pegfilgrastim and daily injection filgrastim in chemotherapy-induced neutropenia: a multicenter dose-finding study in women with breast cancer. Ann Oncol 2002 Jun; 13 (6): 903-9. (Pubitemid 34752686)
55. Sierra J, Szer J, Kassis J, et al. A single dose of pegfilgrastim compared with daily filgrastim for supporting neutrophil recovery in patients treated for lowto- intermediate risk acute myeloid leukemia: results from a randomized, double-blind, phase 2 trial. BMC Cancer 2008; 8: 195.
56. Kotto-Kome AC, Fox SE, Lu W, et al. Evidence that the granulocyte colonystimulating factor (G-CSF) receptor plays a role in the pharmacokinetics of G-CSF and PegG-CSF using a G-CSF-R KO model. Pharmacol Res 2004 Jul; 50 (1): 55-8. (Pubitemid 38479668)
57. Farese AM, Yang BB, Roskos L, et al. Pegfilgrastim, a sustained-duration form of filgrastim, significantly improves neutrophil recovery after autologous marrow transplantation in rhesus macaques. Bone Marrow Transplant 2003 Aug; 32 (4): 399-404. (Pubitemid 37038849)
58. Wang B, Ludden TM, Cheung EN, et al. Population pharmacokinetic- pharmacodynamic modeling of filgrastim (r-metHuG-CSF) in healthy volunteers. J Pharmacokinet Pharmacodyn 2001 Aug; 28 (4): 321-42. (Pubitemid 32953509)
59. Porter CJ, Charman SA. Lymphatic transport of proteins after subcutaneous administration. J Pharm Sci 2000 Mar; 89 (3): 297-310. (Pubitemid 30152431)
60. Supersaxo A, Hein WR, Steffen H. Effect of molecular weight on the lymphatic absorption of water-soluble compounds following subcutaneous administration. Pharm Res 1990 Feb; 7 (2): 167-9. (Pubitemid 20208069)
61. Lau D, Pilz D, Schwab G. Phase I pharmacokinetic and pharmacodynamic studies of G-CSF (filgrastim) in patients with renal or liver impairment compared to healthy volunteers [abstract]. Br J Haematol 1996; 93 Suppl. 2: 277.
62. Yang BB, Kido A, Salfi M, et al. Pharmacokinetics and pharmacodynamics of pegfilgrastim in subjects with various degrees of renal function. J Clin Pharmacol 2008 Sep; 48 (9): 1025-31.
63. Yang B-B, Savin MA, Green M. Prevention of chemotherapy-induced neutropenia with pegfilgrastim: pharmacokinetics and patient outcomes. Am J Hematol Oncol 2011; 10: 13-20.
64. Mayani H. Human preleukemia: cellular, molecular and clinical aspects. Arch Med Res 1993; 24 (4): 317-25. (Pubitemid 24030316)
65. Yang BB, Lum P, Renwick J, et al. Pharmacokinetic rationale for a fixed-dose regimen of a sustained-duration form of filgrastim in cancer patients [abstract]. Blood 2000; 96 (11 Suppl. 1): 157b.
66. George S, Yunus F, Case D, et al. Fixed-dose pegfilgrastim is safe and allows neutrophil recovery in patients with non-Hodgkin's lymphoma. Leuk Lymphoma 2003 Oct; 44 (10): 1691-6. (Pubitemid 37221042)
67. Neulasta- (pegfilgrastim): US prescribing information. Thousand Oaks (CA): Amgen Inc., 2010 [online]. Available from URL: http://pi.amgen.com/uni ted-states/neulasta/neulasta-pi-hcp-english.pdf [Accessed 2011 Jan 19].
68. Aapro MS, Cameron DA, Pettengell R, et al. EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy- induced febrile neutropenia in adult patients with lymphomas and solid tumours. Eur J Cancer 2006 Oct; 42 (15): 2433-53. (Pubitemid 44442936)
69. Burstein HJ. Myeloid growth factor support for dose-dense adjuvant chemotherapy for breast cancer. Oncology (Williston Park) 2006 Dec; 20 (14 Suppl. 9): 13-5.
70. Marangolo M, Bengala C, Conte PF, et al. Dose and outcome: the hurdle of neutropenia (review). Oncol Rep 2006 Aug; 16 (2): 233-48.
71. Danova M, Bencardino K, Manzoni M, et al. In vivo biological effects of pegfilgrastim after myelosuppressive chemotherapy in breast cancer. Anticancer Res 2007 Sep-Oct; 27 (5A): 3399-402. (Pubitemid 47607567)
72. Invernizzi R, Grasso D, Travaglino E, et al. Biological effects of pegfilgrastim on circulating neutrophils in breast cancer patients undergoing dose-dense chemotherapy. Oncology 2008; 75 (3-4): 237-44.
73. Yang BB, Kido A, Shibata A. Serum pegfilgrastim concentrations during recovery of absolute neutrophil count in patients with cancer receiving pegfilgrastim after chemotherapy. Pharmacotherapy 2007 Oct; 27 (10): 1387-93. (Pubitemid 47530445)
74. Pirker R, Ulsperger E, Messner J, et al. Achieving full-dose, on-schedule administration ofACE chemotherapy every 14 days for the treatment of patients with extensive small-cell lung cancer. Lung 2006 Sep-Oct; 184 (5): 279-85. (Pubitemid 46141322)
75. Lopez A, de Sevilla AF, Castaigne S, et al. Pegfilgrastim supports delivery of CHOP-R chemotherapy administered every 14 days: a randomised phase II study [abstract no. 3311]. Blood 2004; 104 (11 Pt 1): 904-5a.
76. Engert A, Bredenfeld H, Dohner H, et al. Pegfilgrastim support for full delivery of BEACOPP-14 chemotherapy for patients with high-risk Hodgkin's lymphoma: results of a phase II study. Haematologica 2006 Apr; 91 (4): 546-9.
77. Data on file, Amgen Inc., 2004-5