Absorption, distribution and excretion of lacidipine, a dihydropyridine calcium antagonist, in rat and dog.
1. The absorption, distribution and excretion of lacidipine have been studied in rat and dog after i.v. (0.05 mg/kg for rat; 0.5 mg/kg for dog) and oral dosage (2.5 mg/kg for rat; 2.0 mg/kg for dog). 2. Lacidipine was rapidly and extensively absorbed after oral dosing, in both species. Oral bioavailability was up to 26% in rat and up to 32% in dog, due to extensive first-pass metabolism. 3. After oral administration, peak levels of radioactivity were reached at 4-8 h in rat and 1-2 h in dog. Unchanged lacidipine peaked at 1-2 h in both species. Plasma levels of radioactivity were higher in female rats than in males but there was no difference in levels of unchanged drug. 4. After i.v. dosing the terminal half-life of unchanged drug was 2.9 h in rat and 8.2 h in dog. The half-life of radioactivity in plasma was longer in both species. 5. After both routes of administration, radioactivity was rapidly distributed in rat tissues with the highest concentration in liver, fat and gastrointestinal tract. Only traces of radioactivity were detected in the CNS and in rat foetuses. 6. Extensive biliary elimination occurred, and most of the radioactivity (73-95%) was excreted in the faeces after i.v. or oral administration. 7. The compound was extensively metabolized, no significant amount of unchanged drug was excreted in bile or urine.
Pellegatti
M
M
Research Laboratories, Glaxo S.p.A., Verona, Italy.
Grossi
P
P
Ayrton
J
J
Evans
G L
GL
Harker
A J
AJ
D000042:Absorption; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001646:Bile / Q000378:metabolism; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004064:Digestive System / Q000378:metabolism; D004095:Dihydropyridines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004285:Dogs; D005243:Feces / Q000737:chemistry; D005260:Female; D008099:Liver / Q000378:metabolism; D008297:Male; D015394:Molecular Structure; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C060285:lacidipine