Intra- and inter-subject variation in the pharmacokinetics of indoramin and its 6-hydroxylated metabolite.
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.
Pierce
D M
DM
Department of Biomedical Research, Wyeth Research (UK) Ltd., Berks, London.
Abrams
S M
SM
Franklin
R A
RA
D000284:Administration, Oral; D006207:Half-Life; D006801:Humans; D007211:Indoles / Q000493:pharmacokinetics*; D007217:Indoramin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male
D007211:Indoles; D007217:Indoramin; C049268:6-hydroxyindoramin