HPLC determination of indalpine and its major metabolite in human plasma and a pharmacokinetic application.
A high-performance liquid chromatographic method using a fluorometric detector was developed for the determination of plasma concentrations of the antidepressant indalpine (I) and its major metabolite 4-[2-(3-indolyl)ethyl]-2-piperidinone (PK). the same procedure was used to measure, in urine, levels of I and of the metabolite, either conjugated or unconjugated. The sensitivity of the assay is 5 ng ml-1 of plasma or urine for both I and PK. Mean recoveries from plasma for PK, I, and the internal standard (quinine sulfate) were 86.4, 86.8, and 88.5 per cent, respectively. Mean recovery from urine for I was 82.5%. This method was used to establish the pharmacokinetic profiles of I and PK following a single oral administration of I (100 mg) in 8 healthy volunteers. Peak plasma concentrations for I and PK were obtained in an average time of 2.1 and 2.6 h (tmax), respectively. The mean absorption t1/2 of I was 0.8 h, the mean Vda 878 l and the mean clearance 58 l h-1. The mean t1/2 for I and PK was 10.4 and 11.9 h, respectively. In a 12 h urine collection 3 per cent of I was excreted unchanged. No conjugated or unconjugated metabolite was found in urine samples. This method was also used to determine plasma levels 10 h post-dose (50 mg t.i.d.) during chronic oral administration in 20 hospitalized patients. Mean plasma concentrations of I and PK post-dose were 116 ng ml-1 and 43 ng ml-1, respectively.
Toupin
L
L
Département de Pharmacologie, Faculté de Médecine Université de Montréal, Canada.
Caillé
G
G
Vézina
M
M
Demontigny
C
C
Tawashi
M
M
D000293:Adolescent; D000328:Adult; D000928:Antidepressive Agents / Q000097:blood* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000097:blood* / Q000493:pharmacokinetics
D000928:Antidepressive Agents; D010880:Piperidines; C054861:4-(2-(3-indoyl)ethyl)-2-piperdinone; C018181:indalpine