Absorption of Paracetamol, Talinolol and Amoxicillin After Oral Administration Using Non-caloric and Caloric Water
Condition: Gastrointestinal Motility Disorder
Study type: Interventional
Phase: Phase 1

Summary: 
      To visualize the localization and to measure the volume of water in the small intestine by
      T2-weighted MRI imaging after oral administration of 240 ml water (non-caloric water) and
      after administration of 240 ml water containing 25.5 g sucrose (105 kcal, caloric water).

      To measure pharmacokinetics of the probe-drugs paracetamol, talinolol and amoxicillin after
      oral administration dissolved in 240 ml non-caloric and in 240 ml caloric water.
    

Detailed description: 
      After swallowing, a drug first is deposited in the stomach together with the co-swallowed
      water. However, the stomach is not the major place of drug absorption. Therefore, the
      kinetics of gastric emptying plays a crucial role for the absorption process. In case of
      dissolved or finely suspended drug particles, gastric emptying of the drugs occurs together
      with gastric contents. The emptied liquid enters the small intestine where it is absorbed.
      Under fasting conditions, the emptied phase consists of the water that was co-swallowed with
      the drug (in clinical studies typically 240 ml) together with a small volume of gastric
      juice. Under fed conditions, the emptied liquid phase is a caloric suspension. It is known
      that both the gastric emptying and the intestinal absorption of pure water are rapid leading
      usually to rapid absorption of water soluble drugs that are taken under fasting conditions.
      In the contrary, delayed absorption under postprandial conditions is typically related to
      delayed gastric emptying. However, velocity and extent of intestinal filling and the
      absorption rate of the liquid phase from gut lumen are unknown.

      Therefore, it is the primary objective of the study to determine the gastric emptying
      kinetics of 240 ml water (non-caloric water) and of 240 ml water containing 25.5 g sucrose
      (105 kcal, caloric water), the respective intestinal filling and the absorption rate of the
      intestinal liquid using water sensitive magnetic resonance imaging (MRI).

      To evaluate the functional meaning of gastric emptying, intestinal filling and water uptake
      for oral drug absorption which are swallowed with non-caloric and caloric water,
      pharmacokinetics of paracetamol, talinolol and amoxicillin will be studied after
      administration with 240 ml non-caloric and 240 ml caloric water, respectively.

      Paracetamol (acetaminophen) was chosen, because it is rapidly and completely absorbed from
      all parts of the gut. The time of its appearance in blood is expected to be a surrogate for
      the rate of gastric emptying. It is hypothesized that caloric content of the water for
      administration does not influence the extent of paracetamol absorption.

      Talinolol represents a well established probe drug for the intestinal efflux transport
      protein ABCB1. Because expression of ABCB1 increases along the small intestine
      (duodenum<jejunum<ileum), we hypothesize, that administration of talinolol with caloric water
      leads to lower bioavailability and increase of the fecal excretion of the drug.

      Amoxicillin acts as a probe drug for intestinal drug uptake via the dipeptide transporter
      PEPT1 which is predominately expressed in proximal parts of the small intestine
      ((duodenum>jejunum>ileum). Because of this region-specific expression, we hypothesize, that
      administration of amoxicillin with caloric water is associated with lower bioavailability.
    

Intervention name(s): Acetaminophen; Talinolol; Amoxicillin; non-caloric water; caloric water
Intervention type(s): Drug; Drug; Drug; Other; Other
Intervention description(s): administration of 500 mg paracetamol; administration of 50 mg talinolol; administration of 500 mg amoxicillin; administration of 240 ml water; administration of 240 ml caloric water (containing 25.5 g sucrose)
Intervention MeSH terms: Acetaminophen; Amoxicillin; Talinolol
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Pharmacokinetics; Talinolol; Amoxicillin; Acetaminophen; Magnetic Resonance Imaging