Effects of a standardized meal on the pharmacokinetics of the new cardiotonic agent piroximone.
The influence of food on the pharmacokinetics of piroximone (MDL 19.205, CAS 84490-12-0) was evaluated in two groups of 6 healthy male volunteers receiving either 25 or 50 mg of the drug. Single doses were administered intravenously and orally under fasting conditions or orally with a standard breakfast on 3 different days with a washout period of at least 3 days in-between doses, according to an open, 3-way crossover, randomized design. Pharmacokinetic parameters (Cmax, tmax, AUC, t1/2, Cl, aVd, UEx) were not affected by food administration, but significant differences were found in t1/2 calculated from the decay of plasma concentrations in response to oral administration of 25 mg and 50 mg treatment doses. The urinary excretion of piroximone was significantly reduced after oral administration, when compared with the values obtained after intravenous application. In addition, extra-renal clearance was significantly reduced in the 50 mg treatment group, when compared with the values obtained in response to 25 mg. Bioavailability of piroximone calculated from AUC data compared favorably with data obtained from urinary recovery results.
Haegele
K D
KD
Marion Merrell Dow Research & Development Center, Strasbourg, France.
Hinze
C
C
Joder-Ohlenbusch
A M
AM
Cremer
G
G
Borlak
J
J
D000293:Adolescent; D000328:Adult; D005502:Food; D006801:Humans; D007093:Imidazoles / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male
D007093:Imidazoles; C039686:piroximone