1: Clin Pharmacokinet. 2007;46(3):261-70.

Alfentanil-induced miosis as a surrogate measure of alfentanil pharmacokinetics
in patients with mild and moderate liver cirrhosis.

Baririan N, Van Obbergh L, Desager JP, Verbeeck RK, Wallemacq P, Starkel P,
Horsmans Y.

Clinical Pharmacology and Gastroenterology Unit, St Luc University Hospital
(Université Catholique de Louvain), Brussels, Belgium.

OBJECTIVES: (i) To evaluate the pupillary response to alfentanil as a surrogate
measure of alfentanil pharmacokinetics in cirrhotic patients and to compare the
data observed in cirrhotic patients with those found in healthy volunteers
(historical control group); and (ii) to compare this test with other liver
function tests in cirrhotic patients. METHODS: Six patients with mild cirrhosis
(Child-Pugh grade A) and six patients with moderate cirrhosis (Child-Pugh grade
B) were studied after a single 15 microg/kg bolus of alfentanil. Alfentanil
plasma concentrations were measured by liquid chromatography-tandem mass
spectrometry, and pupillary responses were measured with a Pupilscan II
pupillometer. Alfentanil pharmacokinetics (plasma concentration, area under the
plasma concentration-time curve from time zero to infinity [AUC(infinity(p))] and
from time zero to 2 hours [AUC(2(p))], apparent volume of distribution at steady 
state, clearance and terminal elimination half-life [t((1/2)(p))]) and miosis
pseudo-kinetic parameters [AUC(infinity)((miosis)), AUC(2)((miosis)),
t((1/2))((miosis))] were determined using a noncompartmental analysis method. In 
six patients (three Child-Pugh grade A and three Child-Pugh grade B), antipyrine 
(measure of liver intrinsic activity) and D-sorbitol (measure of liver blood
flow) tests were performed. RESULTS: A significant correlation was found between 
the alfentanil AUC(infinity(p)) and AUC(infinity)((miosis)) (r = 0.6, p < 0.05)
in cirrhotic patients. This correlation was even more significant if AUC
determinations were limited to the first 2 hours after alfentanil administration 
(r = 0.9, p < 0.01). Statistically significant differences in pharmacokinetics
and miosis pseudo-kinetic parameters were observed between cirrhotic patients and
healthy volunteers from our previous experiment (historical control group). The
correlations were significant between alfentanil clearance and antipyrine
clearance (n = 6, r = 0.9, p < 0.05), alfentanil clearance and steady-state
hepatic blood clearance [CL(H(b))] measured by the D-sorbitol test (n = 6, r =
0.9, p < 0.05). CONCLUSION: Alfentanil pharmacokinetic parameters were correlated
with miosis pseudo-kinetic parameters in cirrhotic patients. There was a
significant decrease in pharmacokinetics and miosis pseudo-kinetics in cirrhotic 
patients compared with volunteers from the historical control group.
Alfentanil-induced miosis has the advantage of being noninvasive and can be
limited to miosis measurements during the first 2 hours after alfentanil
administration in cirrhotic patients. We thus propose to substitute the
AUC(2(miosis)) for alfentanil pharmacokinetics in cirrhosis.

PMID: 17328584 [PubMed - indexed for MEDLINE]

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