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Related Concept Videos

Model Approaches for Pharmacokinetic Data: Physiological Models01:15

Model Approaches for Pharmacokinetic Data: Physiological Models

Physiological models in pharmacokinetics are instrumental in understanding the distribution and elimination of drugs within the body. These models describe the drug concentration within target organs, influenced by factors such as drug uptake, tissue volume, and blood flow. Drug uptake is governed by the partition coefficient, which signifies the drug concentration ratio in tissue to that in the blood. The blood flow rate to a specific tissue is expressed as Qt, and the rate of change in tissue...
Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance01:07

Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance

Drug transporters are critical in drug absorption, distribution, and excretion processes. They should be included in physiological-based pharmacokinetic (PBPK) models, which help predict human drug disposition. However, predicting this is challenging during drug development, especially when liver transport is involved. However, with a realistic representation of body transport processes, an accurate model may be possible.
A recent model describes pravastatin's hepatobiliary excretion, mediated...
Pharmacokinetic Models: Comparison and Selection Criterion01:26

Pharmacokinetic Models: Comparison and Selection Criterion

Physiological and compartmental models are valuable tools used in studying biological systems. These models rely on differential equations to maintain mass balance within the system, ensuring an accurate representation of the dynamic processes at play.
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Measurement of Bioavailability: Pharmacodynamic Methods01:20

Measurement of Bioavailability: Pharmacodynamic Methods

Pharmacodynamic methods provide insights into a drug's effects on physiological processes over time and play a crucial role in understanding bioavailability and therapeutic efficacy. These methods can be broadly classified into acute pharmacological and therapeutic response approaches, each with distinct mechanisms and applications.The acute pharmacological response method directly correlates a drug's physiological effects, such as ECG or pupil diameter changes, to its time course in the body.
Dosage Regimens: Partial Pharmacokinetic Parameters01:01

Dosage Regimens: Partial Pharmacokinetic Parameters

It is not uncommon for complete drug pharmacokinetic profiles to remain elusive in pharmacokinetics. This necessitates certain educated assumptions by pharmacokineticists to determine appropriate dosage regimens without comprehensive pharmacokinetic data from animal or human studies. One prevalent assumption is setting the bioavailability factor, denoted as F, to 1 or 100%. This assumption caters to the scenario where a drug doesn't achieve full systemic absorption, resulting in the patient...
Impact of Pharmacokinetic–Pharmacodynamic Models: Regulatory Decisions01:15

Impact of Pharmacokinetic–Pharmacodynamic Models: Regulatory Decisions

PK–PD modeling has significantly influenced FDA regulatory decisions, particularly drug approval, dosage optimization, and labeling. These models integrate pharmacokinetics (PK) and pharmacodynamics (PD) to predict drug behavior and effects, aiding in optimizing dosing regimens and enhancing the probability of clinical trial success.One notable example is Nesiritide (Natrecor®), a recombinant human brain natriuretic peptide for treating acute decompensated congestive heart failure (CHF).

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Related Experiment Video

Updated: Jun 18, 2026

Humanized NOD/SCID/IL2rγnull (hu-NSG) Mouse Model for HIV Replication and Latency Studies
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Physiologically Based Pharmacokinetic Modelling of Cabotegravir Microarray Patches in Rats and Humans.

Hannah Kinvig1,2, Rajith K R Rajoli1,2, Henry Pertinez1,2

  • 1Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L7 3NY, UK.

Pharmaceutics
|December 23, 2023
PubMed
Summary

This study shows that once-weekly microarray patches (MAPs) delivering cabotegravir can achieve effective drug concentrations for HIV pre-exposure prophylaxis (PrEP). These pain-free MAPs offer a promising alternative for long-acting drug delivery.

Keywords:
HIVMAPPBPKPrEPcabotegravirlong acting

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Area of Science:

  • Pharmacology
  • Drug Delivery Systems
  • Biomedical Engineering

Background:

  • Microarray patches (MAPs) are being explored for self-administered, pain-free, long-acting (LA) drug delivery.
  • Cabotegravir, a potent antiretroviral, shows promise for pre-exposure prophylaxis (PrEP).

Purpose of the Study:

  • To utilize physiologically based pharmacokinetic (PBPK) modeling to characterize cabotegravir's pharmacokinetics via MAPs.
  • To predict optimal dosing strategies for a weekly cabotegravir MAP for HIV PrEP.

Main Methods:

  • A PBPK model was developed and mathematically described for the dissolving bilayer MAP platform.
  • The intradermal PBPK model was validated using existing in vivo rat and human data for cabotegravir.
  • Simulations were performed for once-weekly administrations of 75 mg, 150 mg, and 300 mg cabotegravir MAPs in humans.

Main Results:

  • The PBPK model accurately predicted cabotegravir concentrations from previous studies.
  • All simulated weekly doses (75 mg, 150 mg, 300 mg) maintained concentrations above 4x the target PA-IC90.
  • The 150 mg and 300 mg weekly doses achieved concentrations above 8x the target PA-IC90.

Conclusions:

  • Once-weekly cabotegravir MAPs have the potential for effective HIV PrEP.
  • Practical patch sizes can likely achieve therapeutic cabotegravir concentrations.
  • These findings support further development of cabotegravir MAPs for HIV prevention.