Challenges in the intravenous (IV) administration of monoclonal antibodies (mAbs)

Shire, Steven J.

doi:10.1016/b978-0-08-100296-4.00005-1

Cited by 4 publications

(5 citation statements)

References 27 publications

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“…Drugs administered intravenously do not undergo absorption and presystemic metabolism, and therefore the entire dose reaches the general circulation intact [18]. The intravenous administration is usually given as an infusion rather than a bolus, and thus requires dilution of the mAb formulation, including excipients into appropriate fluids suitable for intravenous administration [22]. The intravenous route causes a high initial plasma concentration.…”

Section: Absorptionmentioning

confidence: 99%

Monoclonal antibodies for severe asthma: Pharmacokinetic profiles

Matera

Calzetta

Rogliani

et al. 2019

Respiratory Medicine

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Several monoclonal antibodies (mAbs) (omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab) are currently approved for the treatment of severe asthma. They have complex pharmacokinetic profiles. These profiles are unique in that they are dependent on their structure as well as can be markedly influenced by the biology of their target antigen, but their general behaviour can still be considered a class property, similar to their endogenous IgG counterpart. They cannot be administered by oral route, have a slow distribution into tissue, are metabolized to peptides and amino acids in several tissues but are protected from degradation by binding to protective receptors (the FcRn), which explains their long elimination half-lives. Their clearance is nonlinear because of the saturation of the target-mediated elimination. Also anti-drug antibody (ADA) response and off-target binding, as well as their glycosylation pattern, can influence the pharmacokinetics of mAbs.

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Section: Absorptionmentioning

confidence: 99%

Monoclonal antibodies for severe asthma: Pharmacokinetic profiles

Matera

Calzetta

Rogliani

et al. 2019

Respiratory Medicine

View full text Add to dashboard Cite

show abstract

“…Also, product compatibility with infusion bags and sets should be ensured due to the possible transit of plastic substances and additives into prepared drug formulation. 16 During product dilution, besides lowering mAb concentration, concentration of excipients, such as surfactants, also decreases. This can lead to antibody aggregation or adsorption to surfaces, which potentially causes patient under-dosing.…”

Section: Formulation Considerationsmentioning

confidence: 99%

“…This can lead to antibody aggregation or adsorption to surfaces, which potentially causes patient under-dosing. 16 Even though many of the listed issues have been successfully overcome, it still remains necessary to prepare mAbs' solutions in aseptic conditions by medical professionals. Challenges of SC drug formulations in many ways differ from infusions.…”

Section: Formulation Considerationsmentioning

confidence: 99%

Pharmacokinetic characterization, benefits and barriers of subcutaneous administration of monoclonal antibodies in oncology

Homšek

Spasić

Nikolić

et al. 2022

J Oncol Pharm Pract

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Objective Therapeutic monoclonal antibodies in oncology are slowly becoming the dominant treatment option for many different cancer types. The main route of administration, infusion, requires extensive product preparations, patient hospitalization and close monitoring. Patient comfort improvement, staff workload reduction and cost savings dictated the development of subcutaneous formulations. The aim of this review is to present pharmacokinetic characteristics of subcutaneous products, discuss the differences between intravenous and subcutaneous routes and to point out the advantages as well as challenges of administration route shift from the formulation development and pharmacometric angle. Data sources Food and Drug administration's Purple book database and electronic medicines compendium were used to identify monoclonal antibodies in oncology approved as subcutaneous forms. Using keywords subcutaneous, monoclonal antibodies, pharmacokinetics, model, as well as specific drugs previously identified, both PubMed and ScienceDirect databases were researched. Data summary There are currently six approved subcutaneous onco-monoclonal antibodies on the market. For each of them, exposure to the drug was similar in relation to infusion, treatment effectiveness was the same, administration was well tolerated by the patients and costs of the medical service were reduced. Conclusion Development of subcutaneous forms for existing and emerging new monoclonal antibodies for cancer treatment as well as shifting from administration via infusion should be encouraged due to patient preference, lower costs and overall lack of substantial differences in efficacy and safety between the two routes.

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“…Here, we reviewed and analyzed the literature published as of the 1 April 2022, describing the different routes of administration used for the delivery of Abs. The IV route has not been considered in this review, being the subject of many reviews elsewhere [ 12 , 13 ] ( Figure 1 ). Each section highlights the basics of the administration route, its application, the potential hurdles, and, when applicable, describes the Abs approved or under review by the regulatory agencies [ 14 , 15 , 16 ], and the molecules in the late stages of clinical trials.…”

Section: Introductionmentioning

confidence: 99%

Alternative Routes of Administration for Therapeutic Antibodies—State of the Art

2022

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Background: For the past two decades, there has been a huge expansion in the development of therapeutic antibodies, with 6 to 10 novel entities approved each year. Around 70% of these Abs are delivered through IV injection, a mode of administration allowing rapid and systemic delivery of the drug. However, according to the evidence presented in the literature, beyond the reduction of invasiveness, a better efficacy can be achieved with local delivery. Consequently, efforts have been made toward the development of innovative methods of administration, and in the formulation and engineering of novel Abs to improve their therapeutic index. Objective: This review presents an overview of the routes of administration used to deliver Abs, different from the IV route, whether approved or in the clinical evaluation stage. We provide a description of the physical and biological fundamentals for each route of administration, highlighting their relevance with examples of clinically-relevant Abs, and discussing their strengths and limitations. Methods: We reviewed and analyzed the current literature, published as of the 1 April 2022 using MEDLINE and EMBASE databases, as well as the FDA and EMA websites. Ongoing trials were identified using clinicaltrials.gov. Publications and data were identified using a list of general keywords. Conclusions: Apart from the most commonly used IV route, topical delivery of Abs has shown clinical successes, improving drug bioavailability and efficacy while reducing side-effects. However, additional research is necessary to understand the consequences of biological barriers associated with local delivery for Ab partitioning, in order to optimize delivery methods and devices, and to adapt Ab formulation to local delivery. Novel modes of administration for Abs might in fine allow a better support to patients, especially in the context of chronic diseases, as well as a reduction of the treatment cost.

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Challenges in the intravenous (IV) administration of monoclonal antibodies (mAbs)

Cited by 4 publications

References 27 publications

Monoclonal antibodies for severe asthma: Pharmacokinetic profiles

Monoclonal antibodies for severe asthma: Pharmacokinetic profiles

Pharmacokinetic characterization, benefits and barriers of subcutaneous administration of monoclonal antibodies in oncology

Alternative Routes of Administration for Therapeutic Antibodies—State of the Art

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