Pharmacokinetics of nisoldipine. I. Absorption, concentration in plasma, and excretion after single administration of [14C]nisoldipine in rats, dogs, monkey, and swine.
The absorption, disposition and excretion of (+/-) 3-isobutyl-5-methyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-pyridine-3,5-dicarboxylate (nisoldipine, Bay k 5552) have been studied following a single administration of the 14C-labelled compound to rats, dogs, monkey and swine via different routes (intravenous, oral, intraduodenal) in the dose range of 0.05-10 mg.kg-1. [14C]nisoldipine was absorbed rapidly and almost completely. Peak concentrations of radioactivity in plasma were reached 0.9 h (rat), 1.4 h (dog), and 3.6 h (monkey) after oral administration with normalized maximum concentrations being in the same range for all three species (0.49-0.79). The radioactivity was eliminated from plasma with half-lives between 42 h and 54 h within an observation period up to 3 days. The contribution of unchanged [14C]nisoldipine to the concentration of total radioactivity in plasma was low after oral administration (between 0.5% (monkey) and 3.4% (dog) in the peak) indicating an extensive presystemic elimination of this compound. The bioavailability was estimated at 3.4% in rats and 11.7% in dogs. [14C]nisoldipine was highly bound to plasma proteins with free fractions of 0.9-2.9%. The excretion of the radioactivity via urine and feces/bile both after oral and intravenous administration of [14C]nisoldipine occurred rapidly and almost completely within 48 h in all species. Very small residues in the body were recovered at the end of the experiments in rats and dogs (less than 1.6% of the dose). The biliary/fecal route of excretion was preferred in rats, dogs and swine, whereas in monkey 76% of the dose was excreted renally.(ABSTRACT TRUNCATED AT 250 WORDS)
Ahr
H J
HJ
Institute of Pharmacokinetics, Bayer AG, Wuppertal, Fed. Rep. of Germany.
Krause
H P
HP
Siefert
H M
HM
Suwelack
D
D
Weber
H
H
D000042:Absorption; D000284:Administration, Oral; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004285:Dogs; D005260:Female; D007275:Injections, Intravenous; D008253:Macaca mulatta; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D015737:Nisoldipine; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D013552:Swine; D014018:Tissue Distribution; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D001798:Blood Proteins; D002121:Calcium Channel Blockers; D014665:Vasodilator Agents; D015737:Nisoldipine; D009543:Nifedipine