The influence of different formula diets and different pharmaceutical formulations on the systemic availability of paracetamol, gallbladder size, and plasma glucose.
The influence of two liquid formula diets on the systemic availability of paracetamol was investigated in 12 healthy normal volunteers using a liquid and a solid paracetamol dosage form. The diets contained the same balanced amounts, but different patterns of nutrients and different amounts of dietary fiber. Plasma glucose and gallbladder response to the standard meal were used as indicators of gastric emptying. Paracetamol plasma concentrations following application of the liquid dosage form also served as a marker for the gastroduodenal transport of liquid gastric contents. For the liquid dosage form, the plasma concentration time curves did not vary with diet composition. However, with the tablets, a differential effect was observed. Following coingestion with the fiber depleted diet, the rate of systemic availability was reduced more than with the liquid preparation. A further delay was obvious, when the tablets were combined with the meal enriched in dietary fiber. Plasma glucose and gallbladder response did not vary with diet composition. Variations of gastric emptying are unlikely to account for the variability of food effects. Consequently our results illustrate that an interaction of certain meal components with a particular drug dosage form determines the rate of intragastric release of the active compound. This could be shown due to a high standardization of nutrition by using liquid formula diets. Because of the variation of drug release, paracetamol cannot be used as a marker of gastric emptying without taking into account the vehicle necessary for drug application. In contrast to previous studies, our data provide evidence that even balanced test meals retard paracetamol absorption.(ABSTRACT TRUNCATED AT 250 WORDS)
Walter-Sack
I E
IE
Abteilung Klinische Pharmakologie der Medizinischen Klinik, Universität, Heidelberg, FRG.
de Vries
J X
JX
Nickel
B
B
Stenzhorn
G
G
Weber
E
E
D000082:Acetaminophen / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000328:Adult; D001682:Biological Availability; D001786:Blood Glucose / Q000378:metabolism*; D004032:Diet; D005526:Food, Formulated; D005704:Gallbladder / Q000033:anatomy & histology / Q000187:drug effects*; D006801:Humans; D008297:Male; D011897:Random Allocation
D001786:Blood Glucose; D000082:Acetaminophen