Pharmacokinetic Study of Frusemide in Healthy and Cirrhotic Indian Subjects

Abstract

Liver cirrhosis is associated with various complications
such as ascites and fluid retention, progressing to development of
hepatorenal syndrome, further compromising fluid elimination.
Frusemide, a loop diuretic is normally administered to relieve fluid
retentions. The kinetics of frusemide has not been conclusively
reported in the three types of cirrhosis and among Indian subjects. The
aim of the current study was to evaluate the kinetics of frusemide
among healthy and Child's A, B and C cirrhosis and compare with
earlier data.
24 cirrhotic were selected and classified according to the Child's-Pugh
classification. 12 healthy male volunteers were screened and included
in the study. 40 mg of frusemide was administered orally to both
groups and blood samples were withdrawn at various intervals of time
for a duration of 8 hrs. The amount of frusemide present in plasma was
analyzed using HPLC. The volumes of distribution (Vd), area under
curve (AUC), systemic clearance (CL), maximum concentration (Cmax),
time for maximum concentration (tmax) in healthy volunteers were
respectively 4.56 ± 0.15 L, 2258 ± 530.7, 4.97 ± 1.67 L/h, 892 ± 49.4
ng/ml, 85.20± 7.49 mins. Corresponding values in Group A were 5.00
± 0.31 L, 2471 ± 228.6, 6.60 ± 2.90L/h, 1021 ± 47.97 ng/ml and 88.25
V 2.12 mins; in Group B 7.73 ± 1.10 L, 4038 ± 154.7, 8.84 ± 0.45 L/h,
1448 ± 43.20 ng/ml and 120 ± 1.89 mins; In group C cirrhosis 9.69 ±
1.32 L, 4085 ± 131.75, 3.49 ± 1.40 L/h, 1551± 59.02 ng/ml and 185.7
± 2.68 mins respectively. Significant differences at 1% and 5% were
observed among the cirrhotic groups and between healthy v/s cirrhotic
patients.
Data from current study do not correlate with earlier reports, carried
mainly in Western population, due to possibly differences in
instrumentation, etc but a possible genetic interplay should not be ruled
out. Data from cirrhotic patients could not be effectively compared with
earlier studies as kinetics of frusemide has not been conclusively been
reported in the three categories of cirrhosis.

Keywords: Pharmacokinetic, Frusemide, Liver cirrhosis.

Internet Journal of Medical Update Vol. 3 (1) 2008: pp. 2-10