Simplification of Drug Dosage Calculation by Application of the Surface Area Principle

Crawford, John D.; Terry, Mary E.; Rourke, G. Margaret

doi:10.1542/peds.5.5.783

Cited by 149 publications

(9 citation statements)

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“…Simultaneously, 48 age-matched wild type (wt) mice were organized into wt control ( n = 24) and wt-treated ( n = 24) groups. The dosage of SLAB51 (200 bn bacteria/Kg/day) was determined by application of the body surface area principle [ 32 ]. The body weight was monitored during the treatment to ensure single-housed animals received the proper intake of treatment.…”

Section: Methodsmentioning

confidence: 99%

Strategic Modification of Gut Microbiota through Oral Bacteriotherapy Influences Hypoxia Inducible Factor-1α: Therapeutic Implication in Alzheimer’s Disease

Bonfili

Gong

Lombardi

et al. 2021

IJMS

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Dysbiosis contributes to Alzheimer’s disease (AD) pathogenesis, and oral bacteriotherapy represents a promising preventative and therapeutic opportunity to remodel gut microbiota and to delay AD onset and progression by reducing neuroinflammation and amyloid and tau proteins aggregation. Specifically, SLAB51 multi-strain probiotic formulation positively influences multiple neuro-chemical pathways, but exact links between probiotics oral consumption and cerebral beneficial effects remain a gap of knowledge. Considering that cerebral blood oxygenation is particularly reduced in AD and that the decreased neurovascular function contributes to AD damages, hypoxia conditioning represents an encouraging strategy to cure diseases of the central nervous system. In this work, 8-week-old 3xTg-AD and wild-type mice were chronically supplemented with SLAB51 to evaluate effects on hypoxia-inducible factor-1α (HIF-1α), a key molecule regulating host-microbial crosstalk and a potential target in neurodegenerative pathologies. We report evidence that chronic supplementation with SLAB51 enhanced cerebral expression of HIF-1α and decreased levels of prolyl hydroxylase 2 (PHD2), an oxygen dependent regulator of HIF-1α degradation; moreover, it successfully counteracted the increase of inducible nitric oxide synthase (iNOS) brain expression and nitric oxide plasma levels in AD mice. Altogether, the results demonstrate an additional mechanism through which SLAB51 exerts neuroprotective and anti-inflammatory effects in this model of AD.

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Section: Methodsmentioning

confidence: 99%

Strategic Modification of Gut Microbiota through Oral Bacteriotherapy Influences Hypoxia Inducible Factor-1α: Therapeutic Implication in Alzheimer’s Disease

Bonfili

Gong

Lombardi

et al. 2021

IJMS

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“…1 The objective of the current study was to evaluate adult population PK analyses of new molecular entities approved for oncology to determine recommendations for the general dosing approach for adolescents in relevant adult oncology clinical trials. 12 0.75 (based on body metabolic rate), 13 and estimated value from adults were used to predict pediatric CL. The predicted mean CL values were compared with the observed mean CL values.…”

Section: Articlementioning

confidence: 99%

“…Figure1Prediction accuracy of pediatric mean clearance (CL) by different allometric models. Three different allometric scaling exponents, 0.67 (based on body surface area),12 0.75 (based on body metabolic rate),13 and estimated value from adults were used to predict pediatric CL. The predicted mean CL values were compared with the observed mean CL values.…”

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confidence: 99%

Recommendations for Dose Selection for Adolescent Patients in Relevant Adult Oncology Clinical Trials

Leong

Liu

et al. 2021

Clin Pharma and Therapeutics

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Our research supported the dose selection recommendations for adolescents in the US Food and Drug Administration (FDA) Guidance on Inclusion of Adolescent Patients in Adult Oncology Clinical Trials. The FDA Guidance states that for drugs administered as a flat dose in adults and data showing no clinically meaningful effect of body size on drug exposure and toxicity in adults, a minimum body weight threshold may need to be defined to prevent adolescents who have a lower body weight from exceeding adult exposures. Our review of adult population pharmacokinetic analyses of new molecular entities approved for oncology between January 2015 and March 2021 suggested that 40 kg (the approximate median body weight of a 12‐year‐old) is generally the lower end of the body weight range that has no clinically relevant effect on drug pharmacokinetics or safety. The minimum body weight threshold and selection of an appropriate dose for adolescents in relevant adult oncology clinical trials should ultimately be determined based on available data on pharmacokinetics or pharmacodynamics of the investigational drug with consideration of body size effect on drug exposure, toxicity, and efficacy data (if available), the therapeutic index of the drug, and dose‐ and exposure‐response relationships in adults.

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“… 13 , 14 , 15 , 16 In addition, predicting pediatric exposures from adult data based on PopPK model covariates such as clearance (CL) correlation with body size is a standard approach routinely used in drug development. 17 , 18 , 19 , 20 There has been growing regulatory support for the use of PK modeling to inform pediatric dose selection using adult PK data. 21 …”

mentioning

confidence: 99%

Population Pharmacokinetic Model Development and Simulation for Recombinant Erwinia Asparaginase Produced in Pseudomonas fluorescens (JZP‐458)

Lin

Dumas

Kaullen

et al. 2021

Clinical Pharm in Drug Dev

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JZP-458 is a recombinant Erwinia asparaginase produced using a novel Pseudomonas fluorescens expression platform that yields an enzyme expected to lack immunologic cross-reactivity to Escherichia coli-derived asparaginases. It is being developed as part of a multiagent chemotherapeutic regimen to treat acute lymphoblastic leukemia or lymphoblastic lymphoma patients who develop E coli-derived asparaginase hypersensitivity. A population pharmacokinetic (PopPK) model was developed for JZP-458 using serum asparaginase activity (SAA) data from a phase 1, single-dose study (JZP458-101) in healthy adults. Effects of intrinsic covariates (body weight, body surface area, age, sex, and race) on JZP-458 PK were evaluated. The model included SAA data from 24 healthy adult participants from the phase 1 study who received JZP-458: intramuscular (IM) data at 12.5 mg/m 2 (N = 6) and 25 mg/m 2 (N = 6), and intravenous (IV) data at 25 mg/m 2 (N = 6) and 37.5 mg/m 2 (N = 6). Model simulations of adult and pediatric SAA profiles were performed to explore the likelihood of achieving a therapeutic target nadir SAA (NSAA) level ≥0.1 IU/mL based on different administration strategies. PopPK modeling and simulation suggest JZP-458 is expected to achieve 72-hour NSAA levels ≥0.1 IU/mL in 100% of adult or pediatric populations receiving IM administration at 25 mg/m 2 , and in 80.9% of adult and 94.5% of pediatric populations receiving IV administration at 37.5 mg/m 2 on a Monday/Wednesday/Friday (M/W/F) dosing schedule. Based on these results, the recommended starting dose for the phase 2/3 pivotal study is 25 mg/m 2 IM or 37.5 mg/m 2 IV on a M/W/F dosing schedule in pediatric and adult patients.

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Simplification of Drug Dosage Calculation by Application of the Surface Area Principle

Cited by 149 publications

References 0 publications

Strategic Modification of Gut Microbiota through Oral Bacteriotherapy Influences Hypoxia Inducible Factor-1α: Therapeutic Implication in Alzheimer’s Disease

Strategic Modification of Gut Microbiota through Oral Bacteriotherapy Influences Hypoxia Inducible Factor-1α: Therapeutic Implication in Alzheimer’s Disease

Recommendations for Dose Selection for Adolescent Patients in Relevant Adult Oncology Clinical Trials

Population Pharmacokinetic Model Development and Simulation for Recombinant Erwinia Asparaginase Produced in Pseudomonas fluorescens (JZP‐458)

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