Quantitative Pharmacology Approach to Select Optimal Dose and Study the Important Factors in Determining Disposition of Therapeutic Monoclonal Antibody in Pediatric Subjects – Some Considerations

Hardiansyah, Deni; Ng, Chee M.

doi:10.1002/9781119289234.ch13

Cited by 1 publication

(2 citation statements)

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“…Excluding mAbs that have received concurrent initial pediatric indication with adult approval, time lag in the approval of new treatment between adults and children is approximately 5.8 years (range, 1‐12 years). Efforts need to be taken to expedite pediatric drug development and modeling and simulation can play an important role, by improving pediatric trial efficiency, optimizing dose selection, and informing extrapolation‐based drug development from adults to children 2‐6 …”

Section: Mab Id General Adult Dataa Pediatric Dataa Adult Population mentioning

confidence: 99%

“…Efforts need to be taken to expedite pediatric drug development and modeling and simulation can play an important role, by improving pediatric trial efficiency, optimizing dose selection, and informing extrapolation-based drug development from adults to children. [2][3][4][5][6] The importance of pharmacokinetic (PK) evaluation in pediatric drug development is well recognized, and a pediatric PK study is generally recommended before pivotal pediatric trials to ensure the "right" dose in these studies. [7][8][9] The PK of mAbs is primarily affected by body weight, and extrapolation from adults to children may conform to allometry.…”

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Model‐Aided Adults‐to‐Children Pharmacokinetic Extrapolation and Empirical Body Size‐Based Dosing Exploration for Therapeutic Monoclonal Antibodies—Is Allometry a Reasonable Choice?

Langevin

Zhou

et al. 2020

The Journal of Clinical Pharma

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The importance of pharmacokinetic (PK) evaluation in pediatric drug development is well recognized, and a pediatric PK study is generally recommended before pivotal trials to ensure the "right" dose in these studies. The PK of therapeutic monoclonal antibodies (mAbs) is primarily affected by body weight, where adults-to-children extrapolation may conform to allometry. Therefore, PK behavior of mAbs in pediatrics, particularly for those with linear PK, is expected to be predictable based on data in adults. To test this hypothesis, we reviewed published population PK reports of marketed mAbs and assessed model-aided PK extrapolation of mAbs to children (2-17 years) through 5 case studies. For each case study, population PK models were developed based on adult data, with allometric exponents of weight on clearance and volume of distribution fixed as standard values (ie, 0.75 for clearance; 1.0 for volume of distribution), approach 1, or coming from adult model estimates, approach 2. Simulated pediatric PK using these 2 approaches was compared with PK observations in pediatric trials to assess the accuracy in model predictions. For pediatrics 6-17 years, model performance was generally comparable with the 2 approaches. For children < 6 years, no definite conclusion could be made, as only 1 case study enrolled children 2-5 years. Our work supports that PK in children 6-17 years is readily predictable for mAbs with linear PK based on adult data and considering weight effect (allometry). Empirical dosing calculations based on PK simulations with allometry are proposed to convert adult doses to equivalent pediatric doses with exposure matching for mAbs in children 2-17 years.

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Section: Mab Id General Adult Dataa Pediatric Dataa Adult Population mentioning

confidence: 99%

mentioning

confidence: 99%

Model‐Aided Adults‐to‐Children Pharmacokinetic Extrapolation and Empirical Body Size‐Based Dosing Exploration for Therapeutic Monoclonal Antibodies—Is Allometry a Reasonable Choice?

Langevin

Zhou

et al. 2020

The Journal of Clinical Pharma

View full text Add to dashboard Cite

show abstract

Quantitative Pharmacology Approach to Select Optimal Dose and Study the Important Factors in Determining Disposition of Therapeutic Monoclonal Antibody in Pediatric Subjects – Some Considerations

Cited by 1 publication

References 67 publications

Model‐Aided Adults‐to‐Children Pharmacokinetic Extrapolation and Empirical Body Size‐Based Dosing Exploration for Therapeutic Monoclonal Antibodies—Is Allometry a Reasonable Choice?

Model‐Aided Adults‐to‐Children Pharmacokinetic Extrapolation and Empirical Body Size‐Based Dosing Exploration for Therapeutic Monoclonal Antibodies—Is Allometry a Reasonable Choice?

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