Pharmacokinetics, metabolism and bioavailability of the new anti-allergic drug BM 113 Part III: Pharmacokinetics, metabolism, dose dependancy and gender effect after single or repeated administration to human healthy volunteers

A new anti-allergic drug, BM 113 (1-(benzhydryloxyethyl)piperidino-4-ethyla cetate CAS 115313-90-1; BM 113 maleate:. CAS 115313-91-2), with a piperidin ic structure, showing antihistaminic properties was studied after administr ation to healthy human volunteers. The focus was on the pharmacokinetics, t he metabolism, the dose dependancy and gender differences of the pharmacoki netic parameters of BM 113 and its main desacetylated metabolite, BM 212. U nchanged 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 recov ered after 120 h. HPLC dosage of BM 212, using a specific method, showed th at BM 212 represented 62 %1 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 dependancy study realised with 20, 40, 60 and 80 mg oral doses admin istered to 8 healthy volunteers has proven the linearity of the pharmacokin etics 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 concentra tion profile was mono or biexponential. depending on the subject but whatev er the gender. An interindividual variability appeared for both sexes and c aused some variations in the pharmacokinetic parameters.