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Intermittent intravenous (IV) infusion is a method of drug administration where medications are delivered over short infusion periods followed by intervals of no drug delivery. This approach helps to prevent sustained high drug concentrations in the bloodstream, reducing the risk of adverse effects associated with prolonged exposure. Unlike continuous infusion, steady-state concentrations may not be achieved during a single dosing cycle but can be reached through repeated...
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A medication’s effectiveness largely depends on its appropriate dosage and the route of administration. Dosage ensures that a sufficient drug concentration is maintained in the bloodstream to elicit the desired therapeutic effect without causing toxicity. The route of administration affects the drug's bioavailability, rate of absorption, and onset of action, which are crucial for achieving optimal therapeutic outcomes. Drug dosage calculations are critical to tailoring therapy to individual...
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Intestinal Epithelial Regeneration in Response to Ionizing Irradiation
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Irinotecan Hydrochloride Administration Considering Dosing-Time Attenuates Delayed Diarrhea in Rats.

Hideto To1,2, Mari Tomonari1,2, Makoto Myojin1

  • 1Department of Medical Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.

Pharmaceutics
|June 26, 2026
PubMed
Summary

Administering irinotecan hydrochloride (CPT-11) at 21:00 significantly reduced severe delayed diarrhea in rats compared to 9:00 dosing. This chronotherapy approach may minimize CPT-11 side effects by altering drug metabolite concentrations in the gut.

Keywords:
SN-38SN-38 glucuronidedelayed diarrheairinotecan hydrochloridepharmacokinetics

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Area of Science:

  • Pharmacology
  • Gastroenterology
  • Chronobiology

Background:

  • Irinotecan hydrochloride (CPT-11) is a key chemotherapy agent for colorectal and gastric cancers.
  • Delayed diarrhea is a significant adverse effect of CPT-11 treatment.
  • Circadian rhythms influence intestinal function and drug metabolism, suggesting potential for time-dependent effects.

Purpose of the Study:

  • To investigate if adjusting the dosing time of CPT-11 can mitigate CPT-11-induced delayed diarrhea.
  • To explore the relationship between CPT-11 pharmacokinetics, its metabolites, and the occurrence of delayed diarrhea based on administration time.

Main Methods:

  • Rats received CPT-11 at either 9:00 or 21:00.
  • Severity of CPT-11-induced delayed diarrhea was assessed.
  • Concentrations of CPT-11, SN-38, and SN-38 glucuronide (SN-38GL) were measured in blood, intestinal tissues, and contents at various time points.

Main Results:

  • Diarrhea severity was significantly lower in the 21:00 dosing group compared to the 9:00 group.
  • Higher concentrations of the active metabolite SN-38 were found in blood and intestinal tissues/contents 8 hours after 9:00 dosing.
  • Elevated SN-38 in the intestinal tract correlated with increased intestinal injury and more severe diarrhea.

Conclusions:

  • Chronotherapy, specifically evening dosing of CPT-11, may effectively reduce the incidence and severity of delayed diarrhea.
  • Time-dependent variations in SN-38 concentrations within the intestinal tract appear to be a key factor in CPT-11-induced gastrointestinal toxicity.