The effect of ileal brake activators on the oral bioavailability of atenolol in man.
A study was carried out in human volunteers to investigate whether ileal brake activators could alter the bioavailability of atenolol from the small intestine by slowing intestinal transit and thereby increasing the time available for absorption. Oleic acid and a monoglyceride were formulated into modified release capsules that were targeted to the small intestine. Atenolol was either dosed separately or incorporated into one of the capsules. Radiolabelled non-disintegrating tablets were dosed at the same time in order to determine the small intestinal transit time (SITT). Plasma concentrations of atenolol were determined by HPLC. The results showed that in some volunteers an increase in SITT did lead to an increase in the quantity of drug absorbed. However, drug absorption was related not only to the total time spent by the drug in the small intestine but other factors such as the proportion of such time spent at the ileocaecal junction. The study highlights the complexities of exploiting natural gastrointestinal processes to enhance the oral bioavailability of drugs.
Dobson
Clair L
CL
Institute of Pharmaceutical Sciences, Nottingham University, UK.
Davis
Stanley S
SS
Chauhan
Sushil
S
Sparrow
Robert A
RA
Wilding
Ian R
IR
D000284:Administration, Oral; D019540:Area Under Curve; D001262:Atenolol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems / Q000379:methods*; D005772:Gastrointestinal Transit / Q000187:drug effects / Q000502:physiology; D005989:Glycerides / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000378:metabolism*; D019301:Oleic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics
D005989:Glycerides; D019301:Oleic Acid; D001262:Atenolol