ABSTRACT
Penfluridol, 1-[4,4-bis(4-fluorophenyl)butyl]-4-[4-chloro-3-(trifluoromethyl)phenyl]-4-piperidinol, was well absorbed by the rat, rabbit, dog, and man after single oral doses of drug in solution. Penfluridol and its metabolites were widely distributed in tissues of male rats and cleared slowly. The terminal plasma t 1/2 for penfluridol was greater than 40 hr for the rabbit, 227 hr for the dog, and 199 hr for man. Fecal excretion of total radioactivity predominated in the rat, rabbit, and dog whereas in man excretion was evenly divided between urine and feces. The major biotransformation pathways of penfluridol in the rat, rabbit, dog, and man were oxidative N-dealkylation followed by beta-oxidation, conjugation of penfluridol, and conjugation of the acidic metabolites.
Subject(s)
Penfluridol/metabolism , Piperidines/metabolism , Animals , Biotransformation , Dogs , Female , Humans , Kinetics , Male , Penfluridol/blood , Rabbits , Rats , Species Specificity , Time Factors , Tissue DistributionABSTRACT
Plasma intact 14C-mixidine levels in rats increased when the drug was administered intraduodenally with 1:3 and 1:5 molar ratios of 2-naphthalenesulfonic acid. Upon histological examination of the duodenums, similar doses of mixidine combined with 2-naphthalenesulfonic acid produced no dose-related lesions. These and previous observations demonstrate that mixidine absorption may be enhanced by ion-pair formation.
Subject(s)
Intestinal Absorption , Pyrrolidines/metabolism , Animals , Dose-Response Relationship, Drug , Duodenum/drug effects , Hydrogen-Ion Concentration , Intestinal Absorption/drug effects , Male , Naphthalenesulfonates/pharmacology , Pyrrolidines/toxicity , RatsABSTRACT
Tolmetin, a nonsteroidal anti-inflammatory drug, is rapidly absorbed (10 to 20 min) and rapidly excreted (T1/2 congruent to 60 min) and shows a linear dose-plasma level response in the therapeutic dose range. Tolmetin does not affect its own metabolism on chronic administration. Tolmetin is displaced, in vitro, from plasma proteins by salicylic acid. This effect is reflected in minor changes in plasma levels and pharmacokinetic parameters when aspirin and tolmetin are coadministered.
Subject(s)
Pyrroles/metabolism , Tolmetin/metabolism , Aspirin/blood , Biological Availability , Blood Proteins/metabolism , Dose-Response Relationship, Drug , Half-Life , Humans , Kinetics , Male , Protein Binding , Salicylates/blood , Tablets , Tolmetin/administration & dosage , Tolmetin/bloodABSTRACT
GLC and spectrophotometric methods for the determination of tolmetin in plasma were developed. The methods can detect tolmetin in concentrations above 0.5 mug/ml. The plasma levels obtained with a 600-mg dose of tolmetin to a human subject are reported.
