NCT01635608

Absorption of Paracetamol, Talinolol and Amoxicillin After Oral Administration Using Non-caloric and Caloric Water

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: University Medicine Greifswald · Academic / Other
• Sex: All
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

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.

Conditions

• Gastrointestinal Motility Disorder

Interventions

Type	Name	Description
DRUG	Acetaminophen	administration of 500 mg paracetamol
DRUG	Talinolol	administration of 50 mg talinolol
DRUG	Amoxicillin	administration of 500 mg amoxicillin
OTHER	non-caloric water	administration of 240 ml water
OTHER	caloric water	administration of 240 ml caloric water (containing 25.5 g sucrose)

Timeline

• Start date: 2011-04-01
• Primary completion: 2011-07-01
• First posted: 2012-07-09
• Last updated: 2012-07-09

Locations

1 site across 1 country: Germany