Avtor/Urednik		Budihna, Metka V; Strojan, Primož; Trampuš-Bakija, Alenka; Grebenc, Helena; Ilievski, Vladimir; Japelj, Irena; Aščerić, Mensura; Zorc-Pleskovič, Ruda; Prevorčnik, Ana; Skitek, Milan
Naslov		Inhibition of intestinal absorption of digoxin by different Ca2+ channel blockers in guinea-pig in vivo and in vitro
Tip		članek
Vir		Period Biol
Vol. in št.		Letnik 99, št. 4
Leto izdaje		1997
Obseg		str. 523-7
Jezik		eng
Abstrakt		Concomitant administration of digoxin and calcium channel blockers (CaB) increases the plasma level of digoxin. One of the possible mechanisms of this interaction could also be the influence of CaB upon enteral absorption of digoxin. This possibility was examined in guinea-pigs in vivo and in vitro. In vivo studies were performed with increasing doses of different CaB (diltiazem, verapamil, nefidipine, nirendipineand nicardipine - the last in (+-), (+) and (-) optical forms). The iv minimal lethaldose (MLD) of digoxin was determine in 1) untreated animals, 2) in animals pretreated with one MLD of digoxin intraduodenally (id), 3) in animals pretreated with one of the CaB iv, 4) in animals pretreated with one of the CaB iv and then with one MLD of digoxin id. Pretreatment with most of the CaB used did not affect the iv MLD of digoxin. However, the iv MLD of digoxin after its id administration was increased in animals pretreated with one of the CaB. These results indicate that, under our experimental conditions, most of the CaB used inhibited the enteral absorption of digoxin. However, the iv MLD of digoxin after its id administration was increased in animals pretreated with one of the CaB. These results indicate that, under our experimental conditions, most of the Cab used inhibited the enteral absorption of digoxin. This inhibition was dose-dependent, and in the case of nicardipine dependent upon its optical activity. In experiments with everted isolated ileum in vitro diltiazem and verapamil inhibited the transfer of digoxin through the instestinal wall. Diltiazem in the groups treated with id plus digoxin iv detached the serosa from underlying muscular coat. Results of our experiments indicate probable involvement of calcium ions in the process of enteral absorption of digoxin inguinea-pig. The mechanism of the described interaction is not known yet.
Deskriptorji		INTESTINAL ABSORPTION DIGOXIN CALCIUM CHANNEL AGONISTS JEJUNUM GUINEA PIGS VERAPAMIL DILTIAZEM NITRENDIPINE