The pharmacokinetics of octreotide in cirrhosis and in healthy man.
OBJECTIVE
The aim of the study was to evaluate the pharmacokinetics of octreotide in patients with cirrhosis compared to healthy volunteers.


METHODS
Seventeen patients with cirrhosis and nine normals received an intravenous bolus of octreotide (0.75 microgram/kg), followed by a continuous infusion of 0.75 microgram.kg-1.h-1 for 12 h. Eight patients were decompensated with ascites, while nine were without signs of decompensation. Serum octreotide levels were followed by blood sampling during the infusion period and for 24 h afterwards.


RESULTS
The average clearance (+/-SEM) was 151 +/- 15 ml/min in normals compared to 102 +/- 9 (p < 0.05) and 105 +/- 9 (p < 0.05) in patients with compensated and decompensated cirrhosis, respectively. The average area under the serum octreotide curve was significantly increased by 53% (p < 0.05) in decompensated and 46% (p < 0.05) in compensated cirrhosis compared to healthy volunteers, while no difference was observed between the groups with cirrhosis. This difference was also reflected by an increased maximum serum concentration during the infusion period of 9797 +/- 580 ng/l in the patients with cirrhosis compared to 7081 +/- 547 ng/l (p = 0.006) in normals. The serum half-life for the beta-phase (T1/2 beta) was 165 +/- 26 min in normals, 200 +/- 21 min in the compensated and 216 +/- 26 min in the decompensated group (NS). The volume of distribution (Vd beta) showed no difference between the three groups. Because of the slow equilibration between plasma and ascitic fluid in decompensated cirrhosis, the calculated clearance may have been overestimated and T1/2 beta and Vd beta underestimated in these patients.


CONCLUSIONS
The present study demonstrates that the pharmacokinetics of octreotide in cirrhosis is substantially different from that found in normals.
Ottesen
L H
LH
Surgical Department L, Aarhus University Hospital, Denmark.
Flyvbjerg
A
A
Jakobsen
P
P
Bendtsen
F
F
D000328:Adult; D000368:Aged; D006207:Half-Life; D006728:Hormones / Q000493:pharmacokinetics*; D006801:Humans; D007275:Injections, Intravenous; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000097:blood / Q000493:pharmacokinetics*; D012016:Reference Values
D006728:Hormones; D015282:Octreotide