Considerations for Optimizing Dosing of Immunoglobulins Based on Pharmacokinetic Evidence
Immunoglobulins (IGs) are widely used for the treatment of immunodeficiency syndromes and several autoimmune diseases. In neonates, IGs have been used for the treatment of alloimmune thrombocytopenia, in neonatal infections and in the rare cases of neonatal Kawasaki disease. This review aims to exam...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-06-01
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| Series: | Antibodies |
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| Online Access: | https://www.mdpi.com/2073-4468/9/2/24 |
| _version_ | 1797564715413536768 |
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| author | Iftekhar Mahmood Million A. Tegenge Basil Golding |
| author_facet | Iftekhar Mahmood Million A. Tegenge Basil Golding |
| author_sort | Iftekhar Mahmood |
| collection | DOAJ |
| description | Immunoglobulins (IGs) are widely used for the treatment of immunodeficiency syndromes and several autoimmune diseases. In neonates, IGs have been used for the treatment of alloimmune thrombocytopenia, in neonatal infections and in the rare cases of neonatal Kawasaki disease. This review aims to examine the various dosing regimens of IGs following intravenous (IV) and subcutaneous (SC) administration, pharmacokinetics (PK) of IGs, and the importance of trough values for the prevention of infections in patients with primary immune deficiency (PID). The review also focuses on the mechanism of catabolism of IGs and the impact on the half-life of IGs. Data and reviews were obtained from the literature and the FDA package inserts. The authors suggest that for dosing, the PK of IGs should be evaluated on the baseline-corrected concentrations since this approach provides an accurate estimate of half-life and clearance of IGs. We also suggest employing clearance as a primary PK parameter for dosing determination of IGs. We suggest that IV dosing would be more effective if given more frequently to adjust for the increased clearance at high doses and because the baseline-corrected half-life is much shorter than the baseline-uncorrected half-life. Regarding SC administration, the dose should be adjusted based on the absolute bioavailability (determined against IV dosing) of the product. Finally, we highlight clinical and PK data gaps for optimum and individualized dosing of IGs. |
| first_indexed | 2024-03-10T19:01:53Z |
| format | Article |
| id | doaj.art-12223b8a09e44d85871a8bdf09b22bba |
| institution | Directory Open Access Journal |
| issn | 2073-4468 |
| language | English |
| last_indexed | 2024-03-10T19:01:53Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibodies |
| spelling | doaj.art-12223b8a09e44d85871a8bdf09b22bba2023-11-20T04:21:41ZengMDPI AGAntibodies2073-44682020-06-01922410.3390/antib9020024Considerations for Optimizing Dosing of Immunoglobulins Based on Pharmacokinetic EvidenceIftekhar Mahmood0Million A. Tegenge1Basil Golding2Division of Clinical Evaluation and Pharmacology/Toxicology, Office of Tissue and Advanced Therapies (OTAT), Center for Biologics Evaluation and Research (CBER), Food & Drug Administration (FDA), 10903 New Hampshire Avenue, Silver Spring, MD 20993, USAOffice of Biostatistics & Epidemiology, Center for Biologics Evaluation and Research (CBER), Food & Drug Administration (FDA), 10903 New Hampshire Avenue, Silver Spring, MD 20993, USADivision of Plasma Protein Therapeutics, Office of Tissue and Advanced Therapies (OTAT), Center for Biologics Evaluation and Research (CBER), Food & Drug Administration (FDA), 10903 New Hampshire Avenue, Silver Spring, MD 20993-0002, USAImmunoglobulins (IGs) are widely used for the treatment of immunodeficiency syndromes and several autoimmune diseases. In neonates, IGs have been used for the treatment of alloimmune thrombocytopenia, in neonatal infections and in the rare cases of neonatal Kawasaki disease. This review aims to examine the various dosing regimens of IGs following intravenous (IV) and subcutaneous (SC) administration, pharmacokinetics (PK) of IGs, and the importance of trough values for the prevention of infections in patients with primary immune deficiency (PID). The review also focuses on the mechanism of catabolism of IGs and the impact on the half-life of IGs. Data and reviews were obtained from the literature and the FDA package inserts. The authors suggest that for dosing, the PK of IGs should be evaluated on the baseline-corrected concentrations since this approach provides an accurate estimate of half-life and clearance of IGs. We also suggest employing clearance as a primary PK parameter for dosing determination of IGs. We suggest that IV dosing would be more effective if given more frequently to adjust for the increased clearance at high doses and because the baseline-corrected half-life is much shorter than the baseline-uncorrected half-life. Regarding SC administration, the dose should be adjusted based on the absolute bioavailability (determined against IV dosing) of the product. Finally, we highlight clinical and PK data gaps for optimum and individualized dosing of IGs.https://www.mdpi.com/2073-4468/9/2/24immunoglobulinsneonatesprimary immune deficiencyclearancehalf-lifedose |
| spellingShingle | Iftekhar Mahmood Million A. Tegenge Basil Golding Considerations for Optimizing Dosing of Immunoglobulins Based on Pharmacokinetic Evidence Antibodies immunoglobulins neonates primary immune deficiency clearance half-life dose |
| title | Considerations for Optimizing Dosing of Immunoglobulins Based on Pharmacokinetic Evidence |
| title_full | Considerations for Optimizing Dosing of Immunoglobulins Based on Pharmacokinetic Evidence |
| title_fullStr | Considerations for Optimizing Dosing of Immunoglobulins Based on Pharmacokinetic Evidence |
| title_full_unstemmed | Considerations for Optimizing Dosing of Immunoglobulins Based on Pharmacokinetic Evidence |
| title_short | Considerations for Optimizing Dosing of Immunoglobulins Based on Pharmacokinetic Evidence |
| title_sort | considerations for optimizing dosing of immunoglobulins based on pharmacokinetic evidence |
| topic | immunoglobulins neonates primary immune deficiency clearance half-life dose |
| url | https://www.mdpi.com/2073-4468/9/2/24 |
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