1: J Clin Pharmacol. 2005 Dec;45(12):1434-41. 

Alfentanil-induced miosis clearance as a liver CYP3A4 and 3A5 activity measure
in healthy volunteers: improvement of experimental conditions.

Baririan N, Horsmans Y, Desager JP, Verbeeck R, Vanbinst R, Wallemacq P, Van
Obbergh L.

Department of Gastroenterology, Cliniques Universitaires Saint-Luc, Avenue
Hippocrate, 10, Brussels 1200, Belgium.

The aims of this study were to demonstrate the correlation between
alfentanil-induced miosis evaluation and alfentanil pharmacokinetics (PK) as a
CYP3A4 and 3A5 activity probe in volunteers and to explain the variability in
pupilar response and in alfentanil PK. In ambient light, the miosis kinetic
parameters were significantly correlated with PK (CLs: r = 0.9, P = .00; AUCs: r
= 0.8, P = .01). In dark, a similar correlation was observed between miosis and
alfentanil clearances (r = 0.85, P = .03). In 6 volunteers, the sigmoid E(max)
model was applicable (average E(max) = 2.5 +/- 0.7 mm, gamma = 2.5 +/- 1.6 and
EC(50) = 76.8 +/- 22.3 ng/mL), and in 3, the simple E(max) model was applicable
(average E(max) = 2.8 +/- 0.3 mm and EC(50) = 19.9 +/- 8.5 ng/mL). There was a
large interindividual variability in PK parameters (coefficient of variation =
19.7%-31.2%). Free drug fraction concentrations were negatively correlated with
plasma alpha(1)-AGP (r = -0.9, P = .04) and albumin levels (r = -0.94, P = .02).
Alfentanil-induced miosis clearance as a noninvasive CYP3A4 and 3A5 activity
measure can be done in both ambient and dark conditions. Drug free fraction may
be responsible for large intersubject variability in alfentanil PK.

Publication Types:
    Clinical Trial

PMID: 16291719 [PubMed - indexed for MEDLINE]