In Silico Dose Prediction for Long-Acting Rilpivirine and Cabotegravir Administration to Children and Adolescents

Rajoli, Rajith K. R.; Back, David; Rannard, Steve P.; Meyers, Caren L. Freel; Flexner, Charles; Owen, Andrew; Siccardi, Marco

doi:10.1007/s40262-017-0557-x

Cited by 26 publications

(10 citation statements)

References 50 publications

(64 reference statements)

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“…A human blood flow-limited whole-body PBPK model for an IM injectable formulation of rilpivirine and cabotegravir using a first-order drug release rate was generated. 125 The model was able to predict observed clinical data with good accuracy. A flow-limited PBPK model in rat for an intravenous injection of anticancer agents was recently developed.…”

Section: Physiologically Based Pharmacokineticsmentioning

confidence: 91%

“…While quantum dot and metallic formulation PBPK models have been established, 120‐124 the final example of NP formulation models using PBPK modeling we will consider in this review is those for nanocrystal formulation. A human blood flow‐limited whole‐body PBPK model for an IM injectable formulation of rilpivirine and cabotegravir using a first‐order drug release rate was generated 125 . The model was able to predict observed clinical data with good accuracy.…”

Section: Modelingmentioning

confidence: 99%

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The Current Landscape of Novel Formulations and the Role of Mathematical Modeling in Their Development

Cottura

Howarth

Rajoli

et al. 2020

The Journal of Clinical Pharma

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Drug delivery is an integral part of the drug development process, influencing safety and efficacy of active pharmaceutical ingredients. The application of nanotechnology has enabled the discovery of novel formulations for numerous therapeutic purposes across multiple disease areas. However, evaluation of novel formulations in clinical scenarios is slow and hampered due to various ethical and logistical barriers. Computational models have the ability to integrate existing domain knowledge and mathematical correlations, to rationalize the feasibility of using novel formulations for safely enhancing drug delivery, identifying suitable candidates, and reducing the burden on preclinical and clinical studies. In this review, types of novel formulations and their application through several routes of administration and the use of modeling approaches that can find application in different stages of the novel formulation development process are discussed.

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Section: Physiologically Based Pharmacokineticsmentioning

confidence: 91%

Section: Modelingmentioning

confidence: 99%

The Current Landscape of Novel Formulations and the Role of Mathematical Modeling in Their Development

Cottura

Howarth

Rajoli

et al. 2020

The Journal of Clinical Pharma

Self Cite

View full text Add to dashboard Cite

show abstract

“…There are restrictions on the use of INSTIs and rilpivirine in the pediatric population due to lack of data. There is one in silico PBPK dose prediction study that has provided dosing recommendations of LA CR in children and adolescents weighing 15–70 kg 73. No dose prediction studies have been undertaken in children weighing less than 15 kg.…”

Section: Therapeutic Potential In Differing Patient Populationsmentioning

confidence: 99%

<p>Evaluating cabotegravir/rilpivirine long-acting, injectable in the treatment of HIV infection: emerging data and therapeutic potential</p>

Fernández¹,

Halsema²

2019

HIV

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Cabotegravir and rilpivirine long-acting injectable antiretroviral therapy for the treatment of HIV-1 infection brings promise of a new mode of delivery and potential solutions to some problems of oral therapy, but also new challenges and unanswered questions. Adding to the increasing body of evidence for newer two-drug combinations, phase II and phase III trial data to date demonstrate cabotegravir and rilpivirine combination injectable therapy to be non-inferior to selected oral triple-therapy alternatives. Most importantly, this therapy is reported to be acceptable to individuals taking the 4-weekly or 8-weekly injections, despite frequent injection-site reactions. Key outstanding questions include management of missed or delayed dosing, drug interactions and management of virological failure, as well as the efficacy of cabotegravir and rilpivirine in all HIV-1 subtypes. We describe clinical evidence to date and efficacy and challenges in selected populations, including women; those with prior virological failure; individuals with a history of difficulty adhering to oral therapy and individuals with co-infections. We await real-world data and longer-term evidence while moving forward to this new era of antiretroviral therapy.

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“…Other notable new treatment options included cabotegravir/rilpivirine and extended release broadly neutralising antibodies. 4…”

Section: International Paediatric Hiv Workhopmentioning

confidence: 99%

Current perspectives on paediatric HIV management from the Mexico International Aids Society Conference, 2019

Archary

Fairlie

Slogrove

2019

Southern African Journal of HIV Medicine

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While acknowledging the great achievements in getting 23 million people living with HIV to access antiretroviral treatment (ART) globally, there is still more to do in order to close the HIV treatment gap between the paediatric and adult ART programmes, with only 54% of children accessing ART compared to 62% of adults. Furthermore, while tremendous global gains have been made in preventing perinatal and postnatal HIV acquisition, HIV-exposed and uninfected children are still not achieving early childhood developmental outcomes comparable to HIV-unexposed children. In this article, we present highlights from two pre-conference meetings (11th International Workshop on HIV Pediatrics and 5th Workshop on Children and Adolescents HIV Exposed and Uninfected) and the International Aids Society (IAS) meeting held in Mexico in July 2019.

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In Silico Dose Prediction for Long-Acting Rilpivirine and Cabotegravir Administration to Children and Adolescents

Abstract: The reported findings represent a rational platform for the identification of suitable dosing strategies and can inform prospective clinical investigation of long-acting injectable formulations in children and adolescents.

Cited by 26 publications

References 50 publications

The Current Landscape of Novel Formulations and the Role of Mathematical Modeling in Their Development

The Current Landscape of Novel Formulations and the Role of Mathematical Modeling in Their Development

<p>Evaluating cabotegravir/rilpivirine long-acting, injectable in the treatment of HIV infection: emerging data and therapeutic potential</p>

Current perspectives on paediatric HIV management from the Mexico International Aids Society Conference, 2019

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