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Pharmacokinetics: Overview01:10

Pharmacokinetics: Overview

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Pharmacokinetics is a scientific discipline that focuses on the journey of a drug within the body, encompassing four key stages: absorption, distribution, metabolism, and elimination. The first stage, absorption, involves the drug's transfer into the bloodstream. Several factors dictate the extent and speed of this process. For example, the liver often metabolizes oral drugs before they reach systemic circulation, leading to only partial absorption. In contrast, intravenous (IV)...
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Pharmacokinetic Models: Overview01:20

Pharmacokinetic Models: Overview

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Pharmacokinetic models utilize mathematical analysis to achieve a detailed quantitative understanding of a drug's life cycle within the body. They are instrumental in simulating a drug's pharmacokinetic parameters, predicting drug concentrations over time, optimizing dosage regimens, linking concentrations with pharmacologic activity, and estimating potential toxicity.
There are three primary types of models: empirical, compartment, and physiological. Empirical models, with minimal...
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Nonlinear Pharmacokinetics: Overview01:19

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Nonlinear or dose-dependent pharmacokinetics is a phenomenon that occurs when the pharmacokinetic parameters of certain drugs deviate from linear pharmacokinetics at higher doses. These drugs do not follow the expected first-order kinetics, where the rate of drug elimination is directly proportional to the drug concentration. Instead, they exhibit a nonlinear relationship, which can be attributed to several factors.
Nonlinearity can arise due to the saturation of plasma protein-binding or...
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Nonlinear Pharmacokinetics: Causes of Nonlinearity01:22

Nonlinear Pharmacokinetics: Causes of Nonlinearity

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Nonlinearity in drug pharmacokinetics is caused by various factors influencing how a drug is absorbed, distributed, metabolized, and excreted. Understanding these nonlinear processes is crucial for predicting drug behavior in the body and optimizing drug dosing regimens.
Nonlinear drug absorption can occur when the process is rate-limited by solubility, carrier-mediated transport systems, or saturation of the presystemic gut wall or hepatic metabolism. For instance, high doses of riboflavin...
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Biopharmaceutics and Pharmacokinetics: Overview01:28

Biopharmaceutics and Pharmacokinetics: Overview

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Understanding drugs, drug products, and their performance in pharmaceutical science is pivotal. Drugs, whether simple molecules or complex compounds, are designed to interact with the body's biological systems to diagnose, treat, or prevent diseases. Drug products include various delivery systems such as tablets, capsules, injections, and inhalers. The performance of these drug products is gauged by their ability to deliver the active ingredient to the desired site of action at the...
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Cholinergic Antagonists: Pharmacokinetics01:24

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Cholinergic antagonists—such as antimuscarinics—are available in oral, topical, ocular, parenteral, and inhalational formulations. Most antimuscarinics are oral formulations,  while scopolamine is available as a topical patch, and ipratropium and tiotropium are available as inhalation aerosols or powders. Atropine, tropicamide, and cyclopentolate are topically instilled in the eye. Most antimuscarinics are lipid-soluble and readily absorbed from the gastrointestinal tract and...
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Updated: Jan 24, 2026

Intracerebroventricular Delivery of Gut-Derived Microbial Metabolites in Freely Moving Mice
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Beyond the Gut: thyroxine malabsorption, pharmacokinetics, and delivery.

Lawrence Siu-Chun Law1,2, Nicholas Wei Xiang Kuu3,4, Melissa Hui Ting Leong1,2

  • 1Endocrinology Division, Department of Medicine, National University Hospital, Singapore 119074, Singapore.

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|January 23, 2026
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Summary

Refractory hypothyroidism management requires distinguishing true malabsorption from non-adherence. Recent evidence supports rapid absorption protocols and parenteral levothyroxine, including subcutaneous administration, for challenging cases.

Keywords:
intramuscularlevothyroxinemalabsorptionpharmacokineticssubcutaneousthyroid

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Area of Science:

  • Endocrinology
  • Pharmacology
  • Gastroenterology

Background:

  • Refractory primary hypothyroidism involves elevated thyroid-stimulating hormone (TSH) despite high-dose levothyroxine.
  • Differentiating true malabsorption from pseudo-malabsorption (non-adherence) is crucial for effective patient management.
  • Recent frameworks and reviews highlight the need for updated strategies in managing complex levothyroxine absorption issues.

Purpose of the Study:

  • To synthesize recent evidence (post-2023) on refractory hypothyroidism management.
  • To present clinical cases illustrating challenges and solutions in levothyroxine absorption.
  • To discuss emerging levothyroxine formulations and administration routes.

Main Methods:

  • A PubMed search identified 41 relevant publications since 2023.
  • Review of case reports, pharmacological studies, and clinical investigations.
  • Analysis of two clinical cases involving refractory hypothyroidism and absorption issues.

Main Results:

  • Case 1: Pseudo-malabsorption identified in a patient with congenital hypothyroidism, with rapid absorption protocols proving effective.
  • Case 2: True malabsorption confirmed in a patient with papillary thyroid cancer and renal failure, necessitating parenteral (subcutaneous) levothyroxine.
  • No standardized absorption tests exist for parenteral levothyroxine, but pharmacokinetic principles can guide assessment.

Conclusions:

  • Rapid oral levothyroxine absorption protocols offer feasible alternatives.
  • Parenteral levothyroxine, particularly subcutaneous, is a viable option for patients with severe malabsorption.
  • Further research is needed to validate the safety and pharmacokinetics of parenteral levothyroxine formulations.