Related Experiment Video

Updated: Jul 2, 2025

Targeting the Rat's Small Bowel: Long-Term Infusion into the Superior Mesenteric Artery
07:12

Targeting the Rat's Small Bowel: Long-Term Infusion into the Superior Mesenteric Artery

Published on: April 8, 2021

4.3K

Preferential meropenem absorption activated by 1α,25-dihydroxyvitamin D3 and shared with foscarnet, a phosphate

Toshihide Saito1, Yuichi Ichimura1, Masako Oda1

  • 1Department of Pharmaceutics, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari, Tobetsu, Hokkaido, 061-0293, Japan.

Drug Metabolism and Pharmacokinetics
|February 17, 2024
PubMed

Insights

Meropenem (MEPM) is preferentially absorbed in the rat ileum, potentially via a transporter shared with foscarnet. Vitamin D significantly enhances MEPM absorption, suggesting a new route for oral formulations.

Area of Science:

  • Pharmacokinetics and Drug Absorption
  • Gastrointestinal Physiology
  • Molecular Transport Mechanisms

Background:

  • Meropenem (MEPM) is a critical carbapenem antibiotic used for severe infections, currently only available in injectable forms.
  • Developing an oral formulation of MEPM would greatly enhance its clinical utility and patient convenience.
  • Understanding the intestinal absorption characteristics of MEPM is crucial for developing such an oral formulation.

Purpose of the Study:

  • To investigate the absorption characteristics of Meropenem (MEPM) in the rat small intestine.
  • To identify potential transporters and regulatory factors involved in MEPM intestinal absorption.
  • To explore the feasibility of enhancing MEPM absorption for oral drug delivery.

Main Methods:

  • Utilized an in situ loop technique to study MEPM absorption in different segments of the rat small intestine.
  • Employed an in vitro diffusion chamber method to assess mucosal-to-serosal (M-to-S) permeation of MEPM across rat ileal segments.
  • Investigated the effect of foscarnet, glycylsarcosine, thiamine, taurocholic acid, biapenem, and 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) on MEPM absorption and permeation.

Main Results:

  • MEPM showed higher disappearance ratios in the ileum compared to the duodenum and jejunum.
  • Foscarnet significantly reduced MEPM disappearance in the ileum, suggesting shared transport mechanisms.
  • 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) markedly increased MEPM's M-to-S permeation across the ileum by over 7-fold.

Conclusions:

  • Meropenem (MEPM) is preferentially absorbed in the rat ileum, likely involving a Na+-dependent phosphate transporter (NaPi-T) or a related transporter.
  • The absorption of MEPM in the ileum appears to be regulated by 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), indicating a potential pathway for oral drug development.
  • These findings provide a basis for developing novel oral formulations of Meropenem (MEPM).
Keywords:
1α,25-dihydroxyvitamin D(3)FoscarnetIn situ and in vitro discrepancyMeropenem absorptionRat ileum

More Related Videos

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment08:59

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment

Published on: December 3, 2020

7.9K
A Robust Pneumonia Model in Immunocompetent Rodents to Evaluate Antibacterial Efficacy against S. pneumoniae, H. influenzae, K. pneumoniae, P. aeruginosa or A. baumannii09:17

A Robust Pneumonia Model in Immunocompetent Rodents to Evaluate Antibacterial Efficacy against S. pneumoniae, H. influenzae, K. pneumoniae, P. aeruginosa or A. baumannii

Published on: January 2, 2017

14.7K

Related Concept Videos

Drug Elimination by Renal Route: Tubular Secretion01:15

Drug Elimination by Renal Route: Tubular Secretion

Once the process of glomerular filtration is completed, blood carrying unfiltered drug molecules traverses through efferent arterioles and makes its way into the peritubular capillaries in the proximal tubule. A variety of carriers play a pivotal role in actively secreting drugs from these peritubular capillaries into the tubular fluid. The organic anion transporter transfers acidic drugs, against an electrochemical gradient, from the peritubular capillaries into the renal tubule cells and...
2.4K
Methods for Studying Drug Absorption: In situ01:09

Methods for Studying Drug Absorption: In situ

In situ experiments, such as the Doluisio method and Single-Pass Perfusion technique, provide critical insights into drug uptake by simulating in vivo conditions for drug absorption.
The Doluisio method involves perfusing a prepared segment of a rat's small intestine with a solution of radiolabeled drug and a non-absorbable marker. This helps to differentiate between absorbed and non-absorbed drug concentrations. The intestinal segment is connected at both ends using tubing and syringes,...
232
Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry01:20

Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry

Orally administered drugs primarily enter the systemic circulation via passive diffusion through the intestinal membranes. The drug's absorption is influenced by drug stability in the gastrointestinal GI tract, membrane permeability, the surface area available for absorption, luminal drug concentration, and residence time in the lumen. Drug permeability can be enhanced by adjusting the lipophilicity, polarity, or molecular size of the drug, promoting its passive transport across intestinal...
208
Carrier-Mediated Transport01:06

Carrier-Mediated Transport

Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
426
Drug Elimination by Renal Route: Tubular Reabsorption01:22

Drug Elimination by Renal Route: Tubular Reabsorption

During the process of renal excretion, as the glomerular filtrate progresses to the distal convoluted tubule (DCT), drugs that are highly permeable, lipophilic, and nonionized undergo passive reabsorption from the tubular fluid into the surrounding peritubular capillaries. This reabsorption process restricts their elimination through the kidneys. However, the majority of drugs are either weak acids or weak bases, and their ionization level is dependent on pH. By altering the pH of urine, the...
3.4K
Drug Absorption Mechanism: Passive Membrane Transport01:23

Drug Absorption Mechanism: Passive Membrane Transport

Passive transport is a method of drug absorption where small, lipid-soluble drugs can move across the cell membrane. This movement happens along the concentration gradient, which is a natural flow from higher to lower concentration areas. The speed at which the drug moves is directly related to its lipid–water partition coefficient. This means that the more a drug dissolves in lipids, the faster it diffuses or spreads throughout the body. It is important to note that most drugs are either...
3.9K