Pharmacokinetics, metabolism and bioavailability of the new anti-allergic drug BM 113. Part III: Pharmacokinetics, metabolism, dose dependency and gender effect after single or repeated administration to human healthy volunteers.
A new anti-allergic drug, BM 113 (1-(benzhydryloxyethyl)piperidino-4- ethylacetate, CAS 115313-90-1; BM 113 maleate: CAS 115313-91-2), with a piperidinic structure, showing anti-histaminic properties was studied after administration to healthy human volunteers. The focus was on the pharmacokinetics, the metabolism, the dose dependency and gender differences of the pharmacokinetic parameters of BM 113 and its main desacetylated metabolite, BM 212. Unchanged BM 113 was not recovered in plasma or in urine. The elimination of the radioactivity was essentially urinary with about 81% recovered within 24 h. The elimination was completed with 97% of the administered dose recovered after 120 h. HPLC dosage of BM 212, using a specific method, showed that BM 212 represented 62% of the urine radioactivity. The plasma profile of radioactivity was characterized by two decreasing phases with respective half-lives of 3.71 +/- 0.66 h and 24.67 +/- 25.01 h. A dose dependency study realised with 20, 40, 60 and 80 mg oral doses administered to 8 healthy volunteers has proven the linearity of the pharmacokinetics of BM 212 in the studied range. BM 212 disposition after single and repeated BM 113 oral doses in a 14-day study did not vary and permitted to conclude that no auto-induction or auto-inhibition phenomenon was involved. No significant difference between men and women was observed. The concentration profile was mono or biexponential, depending on the subject but whatever the gender. An inter-individual variability appeared for both sexes and caused some variations in the pharmacokinetic parameters.
Duchêne
P
P
ADME Bioanalyses, Mougins, France.
Laneury
J P
JP
Tran
G
G
Ladure
P
P
Ollivier
R
R
Buzas
A
A
Merour
J Y
JY
Houin
G
G
D000328:Adult; D018926:Anti-Allergic Agents / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D010879:Piperazines / Q000378:metabolism / Q000493:pharmacokinetics; D010880:Piperidines / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D011758:Pyrroles / Q000378:metabolism / Q000493:pharmacokinetics; D012727:Sex Characteristics
D018926:Anti-Allergic Agents; D010879:Piperazines; D010880:Piperidines; D011758:Pyrroles; C121324:BM 113; C115651:BM 212