Physiologically-based pharmacokinetic modelling of infant exposure to efavirenz through breastfeeding

Olagunju, Adeniyi; Rajoli, Rajith K. R.; Atoyebi, Shakir; Khoo, Saye; Owen, Andrew; Siccardi, Marco

doi:10.12688/aasopenres.12860.1

Cited by 11 publications

(10 citation statements)

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“…Physiologically‐based pharmacokinetic (PBPK) models have been applied with significant impact during drug development and postmarketing phases and have achieved regulatory acceptance as shown by the recent guidelines of the US Food and Drug Administration and the European Medicines Agency . PBPK models are useful for the prediction of drug–drug interaction (DDI) magnitudes and drug disposition in special populations such as pediatrics, pregnant and breastfeeding women, and patients with liver cirrhosis or renal impairment, for all of whom there are high hurdles to design and conduct clinical trials. In addition, PBPK models have been successfully applied to simulate different routes of administration and for the design of novel formulations.…”

Section: Introductionmentioning

confidence: 99%

A Comprehensive Framework for Physiologically‐Based Pharmacokinetic Modeling in Matlab

Stader

Penny

Siccardi

et al. 2019

CPT Pharmacom & Syst Pharma

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Physiologically‐based pharmacokinetic (PBPK) models are useful tools to predict clinical scenarios for special populations for whom there are high hurdles to conduct clinical trials such as children or the elderly. However, the coding of a PBPK model in a mathematical programming language can be challenging. This tutorial illustrates how to build a whole‐body PBPK model in Matlab to answer specific pharmacological questions involving drug disposition and magnitudes of drug–drug interactions in different patient populations.

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Section: Introductionmentioning

confidence: 99%

A Comprehensive Framework for Physiologically‐Based Pharmacokinetic Modeling in Matlab

Stader

Penny

Siccardi

et al. 2019

CPT Pharmacom & Syst Pharma

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“…Thus, the inclusion of physiological parameters and the mammary glands" transport phenomena is an integral part of breastfeeding simulation. [94,95]…”

Section: Milk Removalmentioning

confidence: 99%

A Review of Quantitative Instruments for Understanding Breastfeeding Dynamics

2021

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More than two decades ago, breastfeeding was recognized as the most effective international preventive health intervention, with the potential to prevent 13% of deaths among children younger than 5 years of age worldwide. [3] Studies have shown that infants who do not receive human milk are at higher risk for a number of medical issues, including necrotizing enterocolitis, [4,5] gastrointestinal and upper respiratory tract illness, [6,7] and urinary tract infections. [8] The World Health Organization suggests that all newborns should consume solely human milk during the first six months of life and continue with proper complementary foods until 2 years of age. [9] Breastfeeding has also been recognized as the ideal source of nourishment and the preferred primary feeding modality for infants by the American Association of Pediatrics. In addition, the US Surgeon General published a "Breastfeeding Call to Action" in 2011, touting the benefits of breastfeeding and encouraging all US families to pursue breastfeeding. [10] This renewed interest in breastfeeding fueled ongoing clinical and industrial investigations addressing different aspects of breastfeeding, including nutrition quality, breastfeeding duration, positioning, sucking and swallowing frequency, and latching effectiveness. [11,12] Throughout this review, we use the term "sucking," which refers to a complex interaction and coordination of an infant's jaw, hyoid bone, palate, pharynx, and tongue to coordinate milk removal during breastfeeding. [13,14] Additionally, the term "sucking microstructure" will be noted in different Breastfeeding, as a unique behavior of the postpartum period and an ideal source of nourishment, is profoundly impacted by the physiology and behavior of both mothers and infants. For more than three-quarters of a century, there has been an ongoing advancement of instruments that permit insight into the complex process of latching during breastfeeding, which includes coordinating sucking, swallowing, and breathing. Despite the available methodologies for understanding latching dynamics, there continues to be a large void in the understanding of infant latching and feeding. The causes for many breastfeeding difficulties remain unclear, and until a clearer understanding of the mechanics involved is achieved, the struggle will continue in the attempts to aid infants and mothers who struggle to breastfeed. In this review, the history of development for the most prominent tools employed to analyze breastfeeding dynamics is presented. Additionally, the importance of the most advanced instruments and systems used to understand latching dynamics is highlighted and how medical practitioners utilize them is reported. Finally, a controversial argument amongst pediatric otolaryngolo gists concerning breastfeeding difficulties is reviewed and the urgent need for quantification of latching dynamics in conjunction with milk removal rate through prospective controlled studies is discussed.

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“…PBPK modeling is especially promising to predict infant exposure where only breastmilk drug concentration data are available. 29 An important consideration in using a PBPK approach in lactation studies is the availability of reliable drug and system parameters for both the maternal model and the “infant submodel” to adequately describe drug absorption, distribution, metabolism, and elimination, including the milk-to-plasma ratio. Predictions from such models may serve as a basis for IRBs to evaluate the safety of prospective studies to evaluate infant exposure in a follow-up clinical lactation study.…”

Section: Defining Key Principles For Acceleration Of Pharmacology Studies In Pregnant and Lactating Women With Hivmentioning

confidence: 99%

Optimizing Pharmacology Studies in Pregnant and Lactating Women Using Lessons From HIV: A Consensus Statement

Eke

Olagunju

Momper

et al. 2020

Clin Pharma and Therapeutics

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18, * on behalf of the participants of the WHO-IMPAACT workshop on "Approaches to Optimize and Accelerate Pharmacokinetic Studies in Pregnant and Lactating Women" † Information on the extent of drug exposure to mothers and infants during pregnancy and lactation normally becomes available years after regulatory approval of a drug. Clinicians face knowledge gaps on drug selection and dosing in pregnancy and infant exposure during breastfeeding. Physiological changes during pregnancy often result in lower drug exposures of antiretrovirals, and in some cases a risk of reduced virologic efficacy. The International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) network and the World Health Organization (WHO)convened Pediatric Antiretrovirals Working Group collaboratively organized a workshop of key stakeholders in June 2019 to define key standards to generate pharmacology data for antiretrovirals to be used among pregnant and lactating women; review the antiretroviral product pipeline; describe key gaps for use in low-income and middleincome countries; and identify opportunities to undertake optimal studies allowing for rapid implementation in the clinical field. We discussed ethical and regulatory principles, systemic approaches to obtaining data for pregnancy pharmacokinetic/pharmacodynamic (PK/PD) studies, control groups, optimal sampling times during pregnancy, and pharmacokinetic parameters to be considered as primary end points in pregnancy PK/PD studies. For lactation studies, the type of milk to collect, ascertainment of maternal adherence, and optimal PK methods to estimate exposure were discussed. Participants strongly recommended completion of preclinical reproductive toxicology studies prior to phase III, to allow study protocols to include pregnant women or to allow women who become pregnant after enrolment to continue in the trial. The meeting concluded by developing an algorithm for design and interpretation of results and noted that recruitment of pregnant and lactating women into clinical trials is critical. BACKGROUND Pregnancy is associated with profound physiologic, immunologic, structural, and inflammatory changes. 1 These dynamic changes occur in the maternal and feto-placental units during pregnancy, and significantly influence the pharmacokinetic (PK) processes of drug absorption, 2 distribution, 3,4 metabolism, 1,5 and excretion. 6 For women living with HIV, altered pharmacokinetics during pregnancy can often result in lower antiretroviral (ARV) drug exposures, 7-9 possibly increasing the risk of treatment failure, 10 maternal HIV disease progression, perinatal transmission, drug resistance, 11 and maternal death. 11 Some guidelines recommend dose adaptation of certain ARVs in pregnancy because of lower drug exposures (lopinavir/ritonavir; darunavir/ritonavir). 12

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Physiologically-based pharmacokinetic modelling of infant exposure to efavirenz through breastfeeding

Cited by 11 publications

References 50 publications

A Comprehensive Framework for Physiologically‐Based Pharmacokinetic Modeling in Matlab

A Comprehensive Framework for Physiologically‐Based Pharmacokinetic Modeling in Matlab

A Review of Quantitative Instruments for Understanding Breastfeeding Dynamics

Optimizing Pharmacology Studies in Pregnant and Lactating Women Using Lessons From HIV: A Consensus Statement

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