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Aims: Information on breastfeeding and safety of biologics in infants is lacking due to difficulties in case collection. We evaluated methods for determining the concentration of biologics in breast milk using a dry filter method that can simplify the collection, storage and transport of breast milk. Methods: To generate dried filter paper (DFP) samples, approximately 30 μL of breast milk was placed onto a Whatman 903 card and punched out. After extraction, the supernatant was measured using an enzyme‐linked immunosorbent assay. Three concentrations of each drug were prepared in liquid breast milk (LBM) and DFP samples to determine their stability up to 28 days after storage at 2–8°C or −20°C for LBM and 25 ± 5°C for DFP. LBM and DFP samples were also provided by nursing mothers using biologics during lactation, and drug concentrations in both samples were compared. The agreement between the two measurement methods was confirmed by Bland–Altman analysis. Results: Breast milk was provided by 12 mothers who used biologics (tocilizumab, abatacept, etanercept, golimumab, sarilumab and belimumab). The coefficients of variation for within‐run and between‐run precision for the six drugs were within 15% for both LBM and DFP, and accuracy was within 90%–110% of the quality controls. After 28 days, concentrations remained at more than 90%. The difference between the values obtained by each method was within the acceptable range of error (−12.1 to +16.6 ng/mL). Conclusions: A method for determining the concentration of biologics using DFP is expected to help improve pharmacotherapy for lactating women. [ABSTRACT FROM AUTHOR]

The quality-assured preparation of crushed and diluted preparations for children is a challenge. In this study, a multicenter study was conducted to validate the preparation method for the quality assurance of baclofen powder, clonidine powder, and hydrocortisone powder prepared from tablets according to a previously established method. In-hospital preparations were prepared at five medical facilities under different crushing and mixing conditions. After storage in closed bottles, in-use bottles, and laminated paper for 120 days, ingredients stability, drug elution, and content uniformity after packaging were evaluated. All three ingredients were maintained at between 90% and 110% of their initial content for 120 days under packaging conditions of 25 ± 2 °C and 60 ± 5% relative humidity, with no change in dissolution in all formulations made at all five facilities. The content uniformity was also acceptable. The established method may contribute to quality-assured pediatric dosage form modification. [ABSTRACT FROM AUTHOR]

The demand for tocilizumab is increasing in women who wish to bear children and who have active rheumatoid arthritis. Described here is a woman with rheumatoid arthritis who discontinued her tocilizumab therapy at the end of the first trimester and resumed it after delivery and where tocilizumab levels in maternal serum, infant serum, and the breast milk were measured. Tocilizumab was not detected in maternal serum just before delivery, or in umbilical cord blood or infant serum after birth. Tocilizumab levels in colostrum after intravenous injection were 0.57% of those in serum. Tocilizumab treatment in the first trimester was not associated with a significant drug level in the fetus at delivery and no fetal complications were noted. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to develop a population pharmacokinetic (PK) model of mycophenolic acid (MPA) in pediatric patients with different diseases., Methods: To develop the PK model, electronic medical records (EMR) of pediatric patients with different diseases who received mycophenolic acid mofetil (MMF) at the National Center for Child Health and Development from February 2013 to May 2022 and the results of the MMF pharmacokinetic study of pediatric complicated frequently relapsing steroid-dependent nephrotic syndrome under the Advanced Medical Care B protocol (JSKDC09 study) from October 2015 to June 2019 were integrated and analyzed. Non-linear mixed-effects modeling was used to 1) develop a cross-disease population PK model and 2) estimate PK parameters (apparent clearance CL/F and Q/F; apparent volume of distribution Vc/F and Vp/F; absorption rate constant Ka) by post-hoc Bayesian methods. Patient backgrounds, concomitant medications, and laboratory data were included in the covariate analysis. Visual predictive checks with bootstrap and predictive correction were performed to evaluate the final model., Results: A total of 249 patients with 1495 measurements were used in the analysis, including 68 with post-liver transplant, 65 with nephrotic syndrome, 28 with post-renal transplant, 31 with autoimmune diseases (17 with lupus nephritis and 14 with other collagen diseases), 13 with hematopoietic stem cell transplantation, and 5 with others from EMR and 39 with nephrotic syndrome from the JSKDC09 study. A two-compartment model with a first-order rate absorption process best explained the PK of MPA. A nonlinear relationship between dose and MPA exposure was observed and described by the power function of the model. The final population mean PK parameter estimates (95 % confidence interval) for non-renal transplant patients and average albumin levels were CL/F 15.2 (13.3, 18.0) L/h/70 kg, Vc/F 15.4 (14.4, 17.2) L, Vp/F 246.8 (159.1, 332.1) L, Q/F 7.0 (5.0, 9.0) L/h, and Ka (without proton pump inhibitor [PPI]) 4.4 (2.4, 4.9) h -1 . Weight, disease (post-renal transplant), and serum albumin level were significant covariates for CL/F, and serum albumin level for Vc/F. The use of PPIs also affected Ka., Conclusions: An integrated population PK model of MPA was developed in children with the following conditions: post-solid organ transplantation, post-HSCTx, autoimmune disease, and nephrotic syndrome. Estimated parameters and parameter covariates were similar to those previously reported. This model is expected to provide useful information for using MPA in various diseases in the Japanese population., Competing Interests: Declarations of competing interest KI reports a research grant for clinical trials and clinical research from Zenyaku Kogyo Co., Ltd. to his institution; consulting fees from Kyowa Kirin Co., Ltd., and Chugai Pharmaceutical Co., Ltd.; honoraria for manuscript writing from Zenyaku Kogyo Co., Ltd.; payment for expert testimony to his institution from Zenyaku Kogyo Co., Ltd.; and serves as a member of the advisory board of Kyowa Kirin Co., Ltd. and Chugai Pharmaceutical Co., Ltd.. KN is a member of advisory groups for Kyowa Kirin Co., Ltd., Toa Eiyo Co., Ltd., Zenyaku Kogyo Co., Ltd., and Taisho Pharmaceutical Co., Ltd.; Lecture fee from Ono Pharmaceutical Co., Ltd., Astellas Pharma Inc., Novo Nordisk Pharma Ltd., Alexion Pharmaceuticals Inc., Sumitomo Pharma Co., Ltd., Sanofi K.K., Otsuka Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., and Miyarisan Pharmaceutical Co., Ltd.; Speaker's bureaus from Sumitomo Pharma Co., Ltd., Chugai Pharmaceutical Co. Ltd., JCR Pharmaceuticals Co., Ltd., Sanofi K.K., Zenyaku Kogyo Co. Ltd., and Kyowa Kirin Co. Ltd.. HN reports grants for regulatory science on facilitating pediatric drug development from Japan Agency for Medical Research and Development; Consulting fees from Tohoku University, Daiichi Sankyo Company, Limited, and Pfizer R&D Japan G.K.; Honoraria for lectures from Japan Pharmaceutical Manufacturers Association, Pfizer Global Supply Japan Inc., Bristol Myers Squibb Company, Chugai Pharmaceutical Co., Ltd., Shionogi & Co., Ltd., and Northern Science Consulting Inc.; and serves as a member of advisory board of Taisho Pharmaceutical Holdings Co., Ltd. for drug development for diabetes, a member of advisory board of Sato Pharmaceutical Co., Ltd. for drug development for dermatology, Chairman of the Committee on Pharmaceutical Affairs of Japan Pediatric Society, and Chairman of the Steering Committee of Japan Society on Developmental Pharmacology and Therapeutics., (Copyright © 2024. Published by Elsevier B.V.)

Competing Interests: Atsuko Murashima received a research grant from Chugai Pharmaceutical, Co. Ltd and speaking fees from Chugai Pharmaceutical Co. Ltd, Astellas Pharma Inc., and UCB Japan Co. Ltd. Each author has confirmed compliance with the journal's requirements for authorship. No competing financial interests exist. All other authors declare no conflict of interest.