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Supportive Care in Cancer : Official... Jan 2018Biosimilars are biological medicines that have been shown to be similar to a reference biological medicine that has already been approved for use. Development of... (Review)
Review
Biosimilars are biological medicines that have been shown to be similar to a reference biological medicine that has already been approved for use. Development of biosimilars is based on a "totality of evidence" approach that involves a series of steps by which biosimilars must demonstrate similarity to a reference product in all aspects of the drug and eliminate any remaining uncertainties. Clinical studies are then considered confirmatory and are performed to show that there are no clinically meaningful differences compared with the reference product in a sensitive patient population. The recombinant human granulocyte colony-stimulating factor (G-CSF) biosimilar EP2006/Zarxio® (filgrastim-sdnz) became the first FDA-approved biosimilar in 2015. This review evaluates how clinical equivalence can be demonstrated with G-CSF biosimilars through the identification of "sensitive" study populations and endpoints. Patients with non-metastatic breast cancer treated in the (neo)adjuvant setting represent a potentially homogenous population, making this a suitable sensitive indication for assessing filgrastim and pegfilgrastim biosimilars compared with reference products. This review includes clinical trials of G-CSF biosimilars in breast cancer, focusing on key aspects of the trials that were necessary to accurately demonstrate clinical equivalence and enable extrapolation to relevant indications, based on guidelines and biostatistical principles.
Topics: Biosimilar Pharmaceuticals; Breast Neoplasms; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans
PubMed: 28929372
DOI: 10.1007/s00520-017-3861-y -
Cancer Research and Treatment Oct 2022Febrile neutropenia (FN) can cause suboptimal treatment and treatment-related mortality (TRM) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab,...
Pegfilgrastim Prophylaxis Is Effective in the Prevention of Febrile Neutropenia and Reduces Mortality in Patients Aged ≥ 75 Years with Diffuse Large B-Cell Lymphoma Treated with R-CHOP: A Prospective Cohort Study.
PURPOSE
Febrile neutropenia (FN) can cause suboptimal treatment and treatment-related mortality (TRM) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP).
MATERIALS AND METHODS
We conducted a prospective cohort study to evaluate the effectiveness of pegfilgrastim prophylaxis in DLBCL patients receiving R-CHOP, and we compared them with the PROCESS cohort (n=485).
RESULTS
Since January 2015, 986 patients with DLBCL were enrolled. Pegfilgrastim was administered at least once in 930 patients (94.3%), covering 90.3% of all cycles. FN developed in 137 patients (13.9%) in this cohort (23.7% in the PROCESS cohort, p<0.001), and 4.2% of all cycles (10.2% in the PROCESS cohort, p<0.001). Dose delay was less common (≥3 days: 18.1% vs. 23.7%, p=0.015; ≥5 days: 12.0% vs. 18.3%, p=0.023) in this cohort than in the PROCESS cohort. The incidence of TRM (3.2% vs. 5.6%, p=0.047) and infection-related death (1.8% vs. 4.5%, p=0.004) was lower in this cohort than in the PROCESS cohort. The 4-year overall survival (OS) and progression-free survival (PFS) rates of the two cohorts were not different (OS: 73.0% vs. 71.9%, p=0.545; PFS: 69.5% vs. 68.8%, p=0.616). However, in patients aged ≥75 years, the 4-year OS and PFS rates were higher in this cohort than in the PROCESS cohort (OS: 49.6% vs. 33.7%, p=0.032; PFS: 44.2% vs. 30.3% p=0.047).
CONCLUSION
Pegfilgrastim prophylaxis is effective in the prevention of FN and infection-related death in DLBCL patients receiving R-CHOP, and it also improves OS in patients aged ≥75 years.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Febrile Neutropenia; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Lymphoma, Large B-Cell, Diffuse; Polyethylene Glycols; Prednisolone; Prednisone; Prospective Studies; Rituximab; Vincristine
PubMed: 34990525
DOI: 10.4143/crt.2021.1168 -
The New England Journal of Medicine Mar 2013A 55-year-old, previously healthy woman received a diagnosis of diffuse large-B-cell lymphoma after the evaluation of an enlarged left axillary lymph node obtained on... (Review)
Review
A 55-year-old, previously healthy woman received a diagnosis of diffuse large-B-cell lymphoma after the evaluation of an enlarged left axillary lymph node obtained on biopsy. She had been asymptomatic except for the presence of enlarged axillary lymph nodes, which she had found while bathing. She was referred to an oncologist, who performed a staging evaluation. A complete blood count and test results for liver and renal function and serum lactate dehydrogenase were normal. Positron-emission tomography and computed tomography (PET–CT) identified enlarged lymph nodes with abnormal uptake in the left axilla, mediastinum, and retroperitoneum. Results on bone marrow biopsy were normal. The patient’s oncologist recommends treatment with six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone with rituximab (CHOP-R) at 21-day intervals. Is the administration of prophylactic granulocyte colony-stimulating factor (G-CSF) with the first cycle of chemotherapy indicated?
Topics: Antineoplastic Combined Chemotherapy Protocols; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Lymphoma, Large B-Cell, Diffuse; Middle Aged; Neoplasms; Neutropenia; Polyethylene Glycols; Practice Guidelines as Topic; Recombinant Proteins
PubMed: 23514290
DOI: 10.1056/NEJMct1210890 -
Journal of Managed Care & Specialty... Sep 2021Pegfilgrastim is available as a prefilled syringe (PFS) and an on-body injector (OBI). Whether the administration method of pegfilgrastim affects the effectiveness and... (Observational Study)
Observational Study
Pegfilgrastim is available as a prefilled syringe (PFS) and an on-body injector (OBI). Whether the administration method of pegfilgrastim affects the effectiveness and health care resources has not been evaluated in the setting of routine care. To compare real-world clinical and economic outcomes between PFS and OBI methods of administration. This was a retrospective observational study in patients diagnosed with breast cancer or non-Hodgkin lymphoma who received myelosuppressive chemotherapy and prophylactic use of pegfilgrastim via PFS or OBI between January 1, 2017, and May 31, 2018, according to MarketScan research databases. A propensity score was used to match the PFS cohort 1:1 to the OBI cohort. Outcomes were compared among the matched cohorts using a generalized linear model and generalized estimating equations with log-link function. 3,152 patients were identified. After matching, the final sample included 2,170 patients, representing 1,085 in each cohort. The incidence of febrile neutropenia (FN) in the first chemotherapy cycle was 1.01% for OBI (95% CI = 0.56-1.82) vs 1.48% for PFS (95% CI = 0.91-2.39; = 0.336). In all chemotherapy cycles (total cycles = 7,467), the FN incidence was 0.91% for OBI (95% CI = 0.64-1.30) vs 1.22% for PFS (95% CI = 0.90-1.64; = 0.214). There was no statistically significant difference in adjusted per-member per-month all-cause total cost health care resource utilization (HCRU) for hospitalizations, emergency department visits, and pharmacy claims. In a matched cohort of patients representing real-world utilization, there was no statistically or clinically meaningful difference in FN incidence between OBI and PFS methods of pegfilgrastim administration. There was no difference in total HCRU or total costs. OBI and PFS methods of administration are both indicated for patients requiring prophylactic pegfilgrastim, which is important considering that biosimilar PFS options are now available. This study was funded by Sandoz, Inc. Wang, Li, and K. Campbell are employees of Sandoz, Inc. Schroader and D. Campbell are employees of Xcenda, which was contracted by Sandoz, Inc., to provide study and manuscript development. McBride reports receiving payment from Sandoz, Inc., as a consultant, unrelated to this study; Coherus for advisory board and speaker engagements; and Pfizer for advisory board participation during the time of this study.
Topics: Adult; Aged; Aged, 80 and over; Data Analysis; Female; Filgrastim; Humans; Injections; Male; Middle Aged; Outcome Assessment, Health Care; Polyethylene Glycols; Retrospective Studies; Syringes; Young Adult
PubMed: 33929269
DOI: 10.18553/jmcp.2021.21010 -
Supportive Care in Cancer : Official... May 2021Lipegfilgrastim has been shown to be non-inferior to pegfilgrastim for reduction of the duration of severe neutropenia (DSN) in breast cancer patients. This open-label,... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of lipegfilgrastim versus pegfilgrastim in elderly patients with aggressive B cell non-Hodgkin lymphoma (B-NHL): results of the randomized, open-label, non-inferiority AVOID neutropenia study.
BACKGROUND
Lipegfilgrastim has been shown to be non-inferior to pegfilgrastim for reduction of the duration of severe neutropenia (DSN) in breast cancer patients. This open-label, non-inferiority study assessed the efficacy and safety of lipegfilgrastim versus pegfilgrastim in elderly patients with aggressive B cell non-Hodgkin lymphoma (NHL) at high risk for chemotherapy-induced neutropenia.
PATIENT AND METHODS
One hundred and one patients (median age, 75 years) were randomized to lipegfilgrastim or pegfilgrastim (6 mg/cycle) during six cycles of R-CHOP21.
RESULTS
Lipegfilgrastim was non-inferior to pegfilgrastim for the primary efficacy endpoint, reduction of DSN in cycle 1. In the per-protocol population, mean (standard deviation) DSN was 0.8 (0.92) and 0.9 (1.11) days in the two groups, respectively; the adjusted mean difference between groups was - 0.3 days (95% confidence interval, - 0.70 to 0.19). Non-inferiority was also demonstrated in the intent-to-treat population. The incidence of severe neutropenia in cycle 1 was 51% (21/41) in the lipegfilgrastim group and 52% (23/44) in the pegfilgrastim group. Very severe neutropenia (ANC < 0.1 × 10/L) in cycle 1 was reported by 5 (12%) patients in the lipegfilgrastim group and 8 (18%) patients in the pegfilgrastim group. However, over all cycles, febrile neutropenia (strict definition) was reported by only 1 (2%) patient in each treatment group (during cycle 1 in the lipegfilgrastim group and cycle 6 in the pegfilgrastim group). The mean time to absolute neutrophil count recovery (defined as ≥ 2.0 × 10/L) was 8.3 and 9.4 days in the two groups, respectively. Serious adverse events occurred in 46% of patients in each group; none were considered treatment-related. Eight patients died during the study (2 in the lipegfilgrastim group, 5 in the pegfilgrastim group, and 1 who died before starting study treatment). No deaths occurred during the treatment period, and all were considered to be related to the underlying disease.
CONCLUSIONS
This study shows lipegfilgrastim to be non-inferior to pegfilgrastim for the reduction of DSN in elderly patients with aggressive B cell NHL receiving myelosuppressive chemotherapy, with a comparable safety profile.
TRIAL REGISTRATION NUMBER
ClinicalTrials.gov identifier NCT02044276; EudraCT number 2013-001284-23.
Topics: Aged; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Incidence; Lymphoma, Non-Hodgkin; Neutropenia; Neutrophils; Polyethylene Glycols
PubMed: 32944800
DOI: 10.1007/s00520-020-05711-7 -
Journal of Managed Care & Specialty... Feb 2023Real-world evidence on the comparative effectiveness of pegfilgrastim biosimilars compared with the originator product is limited. To compare the risk of febrile... (Comparative Study)
Comparative Study
Real-world evidence on the comparative effectiveness of pegfilgrastim biosimilars compared with the originator product is limited. To compare the risk of febrile neutropenia (FN) among users of pegfilgrastim biosimilars (pegfilgrastim-jmdb and pegfilgrastim-cbqv) and the originator product. A retrospective cohort study was conducted using 2019 IBM MarketScan databases to assess comparative effectiveness of pegfilgrastim originator and biosimilars for prevention of FN among patients receiving myelosuppressive chemotherapy. Patients with cancer, including breast, lung, colorectal, esophageal and gastric, pancreatic, prostate, ovarian, and non-Hodgkin lymphomas, initiating myelosuppressive chemotherapy courses were selected. We further selected patients who used pegfilgrastim originator and biosimilars within 3 days of chemotherapy completion. FN-associated hospitalizations were measured by diagnosis codes. After 1:1 propensity score matching, we used equivalence (with a margin of 6%) hypothesis tests to compare FN-related hospitalization risk in the first cycle and across all cycles between biosimilars and originator users. A total of 2,045 patients were included, of which 445 (21.8%) used pegfilgrastim-jmdb, 636 (31.1%) used pegfilgrastim-cbqv, and 964 (47.1%) used pegfilgrastim originator. After matching, 13 out of 445 originator users and 17 out of 445 pegfilgrastim-jmdb users developed FN after the first chemotherapy cycle (risk difference was 0.9%; < 0.001 for equivalence test indicating statistical equivalence). After matching, 14 out of 633 originator users and 16 out of 633 pegfilgrastim-cbqv users developed FN (risk difference was 0.32%; < 0.001 for equivalence test indicating statistical equivalence). Results across all cycles (including the first cycle) were consistent with that in the first cycle. In this real-world study of patients with cancer receiving myelosuppressive chemotherapy, there was no difference in FN risk between patients receiving pegfilgrastim originator and biosimilars in the first cycle and across all cycles. These results add further to the current evidence on pegfilgrastim biosimilars and support wider adoption of pegfilgrastim biosimilars among payers, providers, and patients. Future studies assessing the tolerability, side effects, and other safety issues of pegfilgrastim biosimilars are needed.
Topics: Humans; Male; Antineoplastic Combined Chemotherapy Protocols; Biosimilar Pharmaceuticals; Febrile Neutropenia; Granulocyte Colony-Stimulating Factor; Neoplasms; Polyethylene Glycols; Recombinant Proteins; Retrospective Studies; Comparative Effectiveness Research; Antineoplastic Agents; Filgrastim
PubMed: 36705287
DOI: 10.18553/jmcp.2023.29.2.119 -
Drug Safety Dec 2023Biosimilars are additional treatment options that are approved based on robust analytical and clinical comparisons with their reference biologic. At the time of initial... (Review)
Review
Long-Term Real-World Post-approval Safety Data of Multiple Biosimilars from One Marketing-Authorization Holder After More than 18 Years Since Their First Biosimilar Launch.
BACKGROUND
Biosimilars are additional treatment options that are approved based on robust analytical and clinical comparisons with their reference biologic. At the time of initial approval, the full safety profile of a biosimilar is inferred from the reference biologic. Nonetheless, there are still lingering concerns related to the long-term safety of biosimilars. Therefore, we reviewed the post-approval pharmacovigilance data for eight marketed biosimilars from one Marketing Authorization Holder (MAH) to summarize their safety experience in a real-world setting for up to 18 years since their first biosimilar launch.
METHODS
Post-approval cumulative patient exposure and safety experience for eight Sandoz biosimilars [adalimumab (Hyrimoz), epoetin alfa (Binocrit), etanercept (Erelzi), filgrastim (Zarzio), infliximab (Zessly), pegfilgrastim (Ziextenzo), rituximab (Rixathon), and somatropin (Omnitrope)] was summarized based on the available pharmacovigilance data from Periodic Safety Update Reports (PSURs) and the corresponding health authority-authored PSUR assessment reports, where available, as of 31 January 2023. Exposure to all biosimilars was calculated in patient treatment days (PTD) except for rituximab, which was expressed in number of patient doses (PD).
RESULTS
The combined post-approval cumulative exposure to seven out of the eight marketed Sandoz biosimilars was more than 1.3 billion PTD and for rituximab more than 1.8 million PD. Overall, a critical analysis of the cumulative safety data of all eight Sandoz biosimilar PSURs concluded that the overall benefit-risk profile of each remains favorable and is consistent with the respective reference biologics.
CONCLUSIONS
This is one of the largest reviews of post-approval biosimilar pharmacovigilance data to date by one MAH. The real-world experience of all eight marketed Sandoz biosimilars for up to 18 years demonstrates that Sandoz biosimilars can be used as safely as their respective reference biologics. Therefore, patients and healthcare providers can be confident in the clinical benefit and safety of Sandoz biosimilars. It is reasonable to believe that similar conclusions about safety may be reached for other biosimilars developed and approved to the high standards as are already in place by major health authorities such as the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). The long-term safety of biosimilars demonstrated here provides strong support for the concept of biosimilarity.
Topics: Humans; Biosimilar Pharmaceuticals; Rituximab; Infliximab; Adalimumab; Epoetin Alfa; Marketing; Drug Approval
PubMed: 37902937
DOI: 10.1007/s40264-023-01371-8 -
BioDrugs : Clinical Immunotherapeutics,... Dec 2019The approval of biosimilars in the EU follows a comprehensive scientific assessment based on stringent regulatory standards. While the initial approach to biosimilars... (Review)
Review
The approval of biosimilars in the EU follows a comprehensive scientific assessment based on stringent regulatory standards. While the initial approach to biosimilars was understandably cautious and conservative in that uncharted territory to protect patients' safety, the analytical and scientific progress and accumulated experience with biosimilars continues to reshape regulatory requirements, generally leading to a reduced burden of clinical trials. This trend is expected to continue, for example, by increasingly employing pharmacodynamic endpoints and biomarkers, but much work remains to make this happen, especially for complex molecules with several or unknown mechanisms of action. We reviewed the available guidance and European Public Assessment Reports (EPARs) of biosimilars approved in the EU via the centralised procedure. This review focuses on the nature and extent of clinical confirmation of biosimilarity considered necessary in addition to analytical and functional data. Cases with conflicting results from different parts of the comparability exercise are discussed, with the aim of identifying whether certain elements of the comparability exercise are more important than others in determining biosimilarity. Taken together, analytical and functional comparison is the foundation of any biosimilar development. In addition, pharmacokinetic similarity is an indispensable prerequisite for any biosimilar approval, so careful planning on behalf of the applicant is mandated to avoid potential failure of such studies, for example, because of large interindividual variability, underpowered trial designs or other methodological causes. Comparative pharmacokinetic studies are a basic requirement for biosimilar development and are usually more sensitive than clinical efficacy trials when detecting potential product-related differences. This may explain why a demonstration of equivalent efficacy could not overrule a finding of dissimilar pharmacokinetic profiles in two cases of biosimilar pegfilgrastim. However, the outcome of efficacy trials depends not only on drug exposure but also on proper pharmacological action of the biological substance in vivo. Therefore, the objectives of both types of studies differ. Efficacy trials should usually be designed as equivalence trials to ensure that the efficacy of the biosimilar is neither decreased nor increased compared with the reference product. However, some remaining uncertainty regarding potentially increased efficacy of the biosimilar may be acceptable in exceptional cases, provided that the data from other parts of the comparability exercise clearly support a conclusion of biosimilarity and safety is assured. In contrast, uncertainties regarding potentially inferior efficacy of the biosimilar may not be acceptable at all. We conclude that the EU biosimilar regulatory framework is robust and able to adapt to advancing knowledge and experience and to strike a balance between regulatory standards, patient safety and feasibility of biosimilar development.
Topics: Biosimilar Pharmaceuticals; Drug Approval; Europe; Filgrastim; Humans; Polyethylene Glycols; Therapeutic Equivalency
PubMed: 31541400
DOI: 10.1007/s40259-019-00377-y -
JAMA Network Open Jan 2022Prevention of chemotherapy-induced neutropenia (CIN) and its clinical consequences is an unmet need for which plinabulin, a selective immunomodulating... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Prevention of chemotherapy-induced neutropenia (CIN) and its clinical consequences is an unmet need for which plinabulin, a selective immunomodulating microtubule-binding agent, is being tested.
OBJECTIVE
To demonstrate noninferiority between plinabulin and pegfilgrastim for days of severe neutropenia in cycle 1 in patients with solid tumors treated with docetaxel.
DESIGN, SETTING, AND PARTICIPANTS
The Plinabulin vs Pegfilgrastim for the Prevention of Docetaxel-Induced Neutropenia in Patients With Solid Tumors (PROTECTIVE-1) double-blind phase 3 randomized clinical trial was performed in multiple centers in China, Russia, Ukraine, and the US. Participants included patients with breast, prostate, or non-small cell lung cancer treated with single-agent docetaxel chemotherapy. Data were collected from June 1, 2018, to January 31, 2019. The database was locked on February 18, 2021. Data analysis was based on intention to treat and safety and performed from October 5, 2018, to February 23, 2021.
INTERVENTIONS
Plinabulin, 40 mg, plus placebo or pegfilgrastim, 6 mg, plus placebo.
MAIN OUTCOMES AND MEASURES
The primary end point was day of severe neutropenia in cycle 1. Additional end points included clinical consequences of CIN (febrile neutropenia, hospitalizations, infections, antibiotic use, and modifications of chemotherapy dose), patient-reported outcomes for bone pain score, markers for immune suppression (neutrophil-to-lymphocyte ratio [NLR] of >5), immature neutrophils (band, promyelocyte, and myelocyte counts >0), and safety.
RESULTS
Among the 105 patients included in the analysis (65 [6.19%] women; median age, 59 [range, 31-81] years), the primary end point was met within a noninferiority margin of 0.65 days, with a mean difference of 0.52 days (98.52% CI, 0.40-0.65 days). Grade 4 neutropenia frequency in cycle 1 was not significantly different. Plinabulin had earlier onset of action with less grade 4 neutropenia in week 1 of cycle 1. Plinabulin had fewer adverse clinical consequences with rates of febrile neutropenia (0 of 52 vs 1 of 53 [1.9%]), infections (4 of 52 [7.7%] vs 8 of 53 [15.1%]), chemotherapy dose delay of more than 7 days (2 of 52 [3.8%] vs 3 of 53 [5.7%]), and permanent chemotherapy discontinuation (7 of 52 [13.5%] vs 14 of 53 [26.4%]). Patients receiving plinabulin had significantly less bone pain (difference, -0.67 [95% CI, -1.17 to -0.16]; P = .01) and a better immunosuppressive profile (NLR >5 at day 8, 2 of 52 [3.8%] vs 24 of 51 [46.0%]; P < .001). Plinabulin was well tolerated, with comparable safety to pegfilgrastim.
CONCLUSIONS AND RELEVANCE
Plinabulin has comparable efficacy to pegfilgrastim for the prevention of CIN, with better safety and a better immunosuppressive profile. Plinabulin's same-day dosing compared with pegfilgrastim's next-day dosing offers distinct advantages, including reducing use of health care services.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03102606.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Diketopiperazines; Docetaxel; Double-Blind Method; Female; Filgrastim; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Neutropenia; Polyethylene Glycols; Prostatic Neoplasms; Treatment Outcome
PubMed: 35084480
DOI: 10.1001/jamanetworkopen.2021.45446 -
Cell Proliferation Dec 2009Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is widely used as treatment for granulocytopaenia during cytotoxic chemotherapy; however, optimal...
OBJECTIVES
Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is widely used as treatment for granulocytopaenia during cytotoxic chemotherapy; however, optimal scheduling of this pharmaceutical is unknown. Biomathematical models can help to pre-select optimal application schedules but precise pharmacokinetic properties of the pharmaceuticals are required at first. In this study, we have aimed to construct a pharmacokinetic model of G-CSF derivatives filgrastim and pegfilgrastim in mice.
METHODS
Healthy CD-1 mice and those with cyclophosphamide-induced granulocytopaenia were studied after administration of filgrastim and pegfilgrastim in different dosing and timing schedules. Close meshed time series of granulocytes and G-CSF plasma concentrations were determined. An ordinary differential equations model of pharmacokinetics was constructed on the basis of known mechanisms of drug distribution and degradation.
RESULTS
Predictions of the model fit well with all experimental data for both filgrastim and pegfilgrastim. We obtained a unique parameter setting for all experimental scenarios. Differences in pharmacokinetics between filgrastim and pegfilgrastim can be explained by different estimates of model parameters rather than by different model mechanisms. Parameter estimates with respect to distribution and clearance of the drug derivatives are in agreement with qualitative experimental results.
CONCLUSION
Dynamics of filgrastim and pegfilgrastim plasma levels can be explained by the same pharmacokinetic model but different model parameters. Beause of a strong clearance mechanism mediated by granulocytes, granulocytotic and granulocytopaenic conditions must be studied simultaneously to construct a reliable model. The pharmacokinetic model will be extended to a murine model of granulopoiesis under chemotherapy and G-CSF application.
Topics: Agranulocytosis; Animals; Antineoplastic Agents; Cyclophosphamide; Disease Models, Animal; Filgrastim; Granulocyte Colony-Stimulating Factor; Mice; Models, Biological; Polyethylene Glycols; Recombinant Proteins
PubMed: 19689472
DOI: 10.1111/j.1365-2184.2009.00638.x