PHARMACOKINETICS OF FAMOTIDINE AFTER A SINGLE ORAL DOSE IN PATIENTS WITH LIVER

CIRRHOSIS.

R.Orlando t A.Varotto t F.Lirussi t R.M.Iemmolo~ G.Nassuato t M.Strazzabosco~ M.Bolo-

~na t G.Carlucci~ L.Okolicsanyi

Istituto di Medicina Interna, Universit~ di Padova, Via Giustiniani, 2 - PADOVA Patients with liver cirrhosis are often given H~ receptor antagonists to treat lesions of

the gastrointestinal tract (gastritits and peptlc ulceration). However, little is known about

the kinetics of famotidine, a new H 2 receptor blocking agent. Famotidine was given as a sin-

gle oral dose of 40 mg in seven controls and in twelve patients with liver cirrhosis (CP) and at half dose (20 mg) in other four cirrhotics. Blood samples were collected 1,4,12,24 hours

after oral administration and stored at -20°C until assayed. Famotidine plasma concentrations

were determined by high performance liquid chromatography according to the method of Vincek

et al. (i). The area under the plasma concentration-time curve (AUC) and total body clearan-

ce (CI) were evaluated in each patient and control.

Results: The mean values of AUC's in controls and CP receiving 40 mg were respectively

1000.66 ng/ml/h ~ 289.04 and 2001.65 ng/ml/h ~ 1105.97 SD p < 0.05. Similarly, mean values

for AUC's in CP receiving 20 mg of famotidine were 979.93 ng/ml/h ~ 483.14 SD (p = ns vs

controls). The mean values of famotidine C1 in controls and in CP (40 mg) were respectively

717.49 ml/min + 210.1 and 411.83 ml/min + 162.31 SD p < 0.005.

Conclusions: The pharmacokinetics of famotidine is impaired in patients with compensated

liver cirrhosis receiving a single oral dose of 40 mg of the drug. Therefore, in CP a re-

duction in drug dosage seems advisable.

(I) I.Chromatogr. 1985;338:438

THE ROLE OF ALBUMIN (A) ON ELIMINATION OF INDOCYANINEGREEN (ICG) IN THE INTACT PIG. Peter Ott (*), Susanne Keiding (*), Steen Boesby (~) & Ludvik Bass (-). Dept. A (*) and C (m) Rigshospitalet, Copenhagen, Denmark and University of Queensland (-),Brisbane, Australia.

The role of A on the elimination of albumin bound organic aniones was studied. A 30-40 kg aneasthesied pig was infused at a constant rate with ICG, an organic anion more than 99% albumin bound. After an equilibrium period, blood was sampled from a liver vein (for determination of ICG (Cv)) and the carotic artery (concentration of A and ICG (Ca))(PERIOD i). Then 600-1000 ml of blood was replaced with an identical volume of an isoosmotic mixture of dextrane 70 and pig erytrocytes. The ICG lost by this procedure was substituted and after additional 30 min, blood was sampled for PERIOD 2. Concentrations of ICG were expressed as C=(Ca-Cv)/in(Ca/Cv). In 4 technically succesful preliminary experiments, a decrease in albumin induced an increase of intrinsic clearance calculated as ICG-infusionrate/~. Plasma flow calculated from Ficks principle and plasma volume did not change. These findings indicate that the albumin concentration might be important for the hepatic uptake of organic aniones.

Pig no

Albumin (~mol/l) PERIOD 1 PERIOD 2

Intrinsic clearence (ICG)(1/min) PERIOD 1 PERIOD 2

378 ±i0 231 ±8 .314 ±.003 .413 ±.008 380 ±ii 226 ±3 .454 ±.019 .713 ±.037 408 ±17 289±11 .551 ±.013 .648 ±.022 450 ±6 323 ±3 .377 ±.007 .452 ±.010

(Mean ± 2 SEM of 7 measurements in a 30 min steady state)

$158