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Bioavailability: Influencing Factors01:22

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Bioavailability refers to the extent and rate at which a drug reaches systemic circulation in its active form. Extent refers to the amount of the drug that makes it into circulation, while rate is the speed at which it enters circulation. It is influenced by several factors critical for optimizing drug formulations, dosing regimens, and therapeutic outcomes.Physicochemical properties of drugs and formulationsThe solubility, stability, and dissolution rate of a drug significantly impact its...
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Pharmacokinetics: Drug–Drug Interactions01:25

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Drug interactions occur when the pharmacological effect of one drug is altered by another substance, either enhancing or diminishing its activity. The drug whose activity is altered is known as the object drug, and the substance causing the alteration is called the agent drug or the precipitant. The net effects of these interactions are mostly undesirable, leading to decreased effectiveness or increased adverse effects. In rare cases, interactions can be beneficial, such as the enhanced...
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Drug–drug interactions can precipitate toxicity through multiple mechanisms. Absorption interactions alter how drugs enter the body, exemplified when ranitidine increases the absorption of basic drugs, while cholestyramine decreases the levels of propranolol. Protein binding interactions occur when drugs share the same binding sites on plasma proteins. Drugs like aspirin and warfarin, when bound in excess, can lead to increased free drug concentrations, enhancing the potential for...
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The pharmacokinetic journey of oral drugs begins with a crucial first pass through the hepatic portal system, called the first-pass effect. This first pass significantly impacts bioavailability — the proportion of a drug that enters systemic circulation and is available for therapeutic action. The primary route sees the drug absorbed by intestinal membranes and then shunted to the liver via the hepatic portal vein. Here, pre-systemic elimination occurs as drugs face metabolism or biliary...
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Bioavailability Enhancement: Drug Stability Enhancement and GI Retention01:05

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Improving a drug's stability in the gastrointestinal (GI) tract is paramount for enhancing its bioavailability and therapeutic effectiveness. Various strategies are employed to protect the drug from the harsh gastric milieu and to ensure its release and absorption at the desired site within the GI tract.Polymer coatings are one such method used to shield drugs from the stomach's acidic environment. By preventing premature drug release, these coatings improve the bioavailability of unstable...
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A drug interaction occurs when the concurrent use of another drug, food, or an external substance alters the pharmacological activity of a drug. This interaction can modify the action of the original drug, affecting its effectiveness and safety.Drug–food interactions are significant as they impact drug absorption, metabolism, and excretion. For example, grapefruit juice is a well-known disruptor of drug metabolism. It inhibits the cytochrome P450 3A4 enzyme, crucial for the metabolism of...
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Crushed Posaconazole Delayed-Release Tablets Have Reduced Bioavailability and Interaction With Tacrolimus Relative to

Kathryn Flynn1,2, Haley Hixson1, Samuel L Aitken1

  • 1Department of Pharmacy, University of Michigan, Ann Arbor, MI, USA.

The Annals of Pharmacotherapy
|May 5, 2026
PubMed
Summary
This summary is machine-generated.

Crushing posaconazole delayed-release tablets (DRT) for feeding tubes may lower absorption and therapeutic levels. Switching from crushed to noncrushed DRT increased tacrolimus levels, impacting drug interactions in lung transplant recipients.

Keywords:
antifungalscytochrome P-450 interactionsdrug administrationtacrolimustransplantation

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Area of Science:

  • Pharmacology
  • Transplantation Medicine
  • Clinical Pharmacy

Background:

  • Posaconazole delayed-release tablets (DRT) are sometimes crushed for enteral administration.
  • The impact of crushing DRT on posaconazole absorption and its interaction with tacrolimus is not well understood.
  • This study investigates posaconazole administration routes in lung transplant recipients (LTR).

Purpose of the Study:

  • To evaluate the effect of different posaconazole administration routes on posaconazole and tacrolimus trough concentration-to-dose ratios (C/D) in LTR.
  • To assess the achievement of therapeutic posaconazole levels based on administration route.
  • To analyze tacrolimus C/D changes when switching from crushed to noncrushed posaconazole DRT.

Main Methods:

  • Retrospective analysis of adult LTR receiving tacrolimus and posaconazole prophylaxis.
  • Comparison of posaconazole C/D across noncrushed oral DRT, IV, and crushed DRT routes.
  • Evaluation of tacrolimus C/D and therapeutic posaconazole level attainment.
  • Paired analysis of tacrolimus C/D in patients switching from crushed to noncrushed DRT.

Main Results:

  • Lower median posaconazole C/D was observed with crushed DRT (2.1) compared to IV (4.2) and noncrushed DRT (4.1).
  • Therapeutic posaconazole levels were achieved in only 40% of LTR on crushed DRT versus 86-94% on other routes.
  • Tacrolimus C/D did not significantly differ across initial posaconazole routes (P=0.72), but increased after switching from crushed to noncrushed DRT (7.8 to 9.5; P=0.04).

Conclusions:

  • Crushing posaconazole DRT significantly reduces posaconazole C/D and therapeutic level achievement.
  • Switching from crushed to noncrushed posaconazole DRT increases tacrolimus C/D.
  • Clinicians must consider altered drug levels when administering crushed posaconazole DRT, especially via feeding tubes, to avoid subtherapeutic drug concentrations.