Intra- and inter-subject variation in the pharmacokinetics of indoramin and its 6-hydroxylated metabolite.

Abstract

Intra- and inter-subject variation in the kinetics of indoramin and its active metabolite 6-hydroxyindoramin have been studied in 5 young, healthy, male volunteers administered a single oral dose of the drug on 5 separate occasions. Inter-subject variation represented the main source of variability in indoramin plasma concentrations with, for example, the between-subjects sum of squares (a measure of the contribution to the total variability) representing around 97% of the total sum of squares for Cmax and AUC (0-24). Intra-subject and inter-subject coefficients of variation (C.V.s) were circa 20% and 100% respectively for both these parameters. Variability in 6-hydroxyindoramin concentrations was much lower and was approximately equally derived from intra- and inter-subject variation, with the C.V.s being approximately 44% for both Cmax and AUC (0-24). The results imply that the kinetic behaviour of indoramin within an individual will prove relatively consistent, despite widespread inter-subject variation, once an appropriate dosage regime has been established.