The talinolol double-peak phenomenon is likely caused by presystemic processing after uptake from gut lumen.
OBJECTIVE
Evaluation of the double-peak phenomenon during absorption of the beta(1)-selective blocker talinolol relative to paracetamol, which is well absorbed from all parts of the gut, and relative to vitamin A, which is absorbed via the lymphatic pathway.


METHODS
Talinolol was given with paracetamol and retinyl palmitate in fast-disintegrating, enteric-coated, and rectal soft capsules to 8 fasting male healthy subjects (21-29 years, 68-86 kg). To evaluate whether the talinolol double-peak is associated with processes of food absorption, a breakfast was served 1 h after administration of a fast disintegrating capsule.


RESULTS
Bioavailability of talinolol in enteric-coated and rectal capsules was significantly reduced by about 50% and 80%, respectively, despite unchanged bioavailability of paracetamol. Double-peaks appeared after 2-3 h and 4-6 h with talinolol given as fast-liberating capsules. Food increased the maximum concentrations significantly (223 +/- 76 microg/ml vs. 315 +/- 122 microg/ml, p < 0.05) and shifted the second peak of talinolol to shorter t(max) values (3.8 +/- 1.2 h vs. 2.1 +/- 0.6 h, p < 0.05), which was associated with faster absorption of retinyl palmitate. Pharmacokinetic model fits showed that about half of the oral talinolol dose given with and without meal is drained from the intestine via a presystemic storage compartment.


CONCLUSIONS
The double-peak phenomenon of talinolol is likely caused by a presystemic storage compartment, which represents the complex interplay of heterogeneous uptake and kick-back transport processes along the intestinal-hepatic absorption pathway.
Weitschies
Werner
W
Department of Biopharmacy and Pharmaceutical Technology, Peter Holtz Research Center of Pharmacology and Experimental Therapeutics, Ernst Moritz Arndt University, Greifswald, Germany. werner.weitschies@uni-greifswald.de
Bernsdorf
Annika
A
Giessmann
Thomas
T
Zschiesche
Michael
M
Modess
Christiane
C
Hartmann
Vera
V
Mrazek
Claudia
C
Wegner
Danilo
D
Nagel
Stefan
S
Siegmund
Werner
W
D000082:Acetaminophen / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D000284:Administration, Oral; D000285:Administration, Rectal; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002214:Capsules; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D004224:Diterpenes; D004334:Drug Administration Schedule; D005780:Gelatin; D006207:Half-Life; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D019518:Postprandial Period; D011412:Propanolamines / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D000084562:Retinyl Esters; D013997:Time Factors; D014801:Vitamin A / Q000031:analogs & derivatives / Q000097:blood
D002214:Capsules; D003692:Delayed-Action Preparations; D004224:Diterpenes; D011412:Propanolamines; D000084562:Retinyl Esters; D014801:Vitamin A; C014794:retinol palmitate; D000082:Acetaminophen; C011550:talinolol; D005780:Gelatin