Pharmacokinetics of the somatostatin analog lanreotide in patients with severe chronic renal insufficiency.

Objective: To characterize the pharmacokinetic profile of the somatostatin analog lanreotide in patients with severe chronic renal insufficiency.

Methods: Lanreotide was administered by intravenous bolus (7 microg/kg) to 12 patients with severe chronic renal insufficiency and to 12 healthy subjects. Lanreotide serum levels were determined by a radioimmunoassay procedure from time 0 until 24 hours after the administration. The main pharmacokinetic parameters were estimated by a noncompartmental treatment of data.

Results: The total serum clearance of lanreotide was found to be significantly lower in patients with severe chronic renal insufficiency than in healthy subjects (mean +/- SEM values of 0.138 +/- 0.017 L/hr/kg versus 0.244 +/- 0.027 L/hr/kg; P < .005). The initial lanreotide concentration, the elimination half-life, the area under the curve from time zero to 24 hours, and the area under the curve from time zero to infinity were significantly greater in patients with severe chronic renal insufficiency than in healthy subjects (307.45 +/- 79.19 ng/mL versus 127.18 +/- 22.65 ng/mL [P < .05]; 2.39 +/- 0.33 hours versus 1.32 +/- 0.20 hours [P < .005]; 62.55 +/- 9.73 ng/mL x hr versus 32.09 +/- 3.23 ng/mL x hr [P < .005]; and 62.95 +/- 9.78 ng/mL x hr versus 32.30 +/- 3.23 ng/mL x hr [P < .005], respectively). The initial volume of distribution, but not the volume of distribution at steady state, was significantly lower in patients with severe chronic renal insufficiency (0.040 +/- 0.008 L/kg versus 0.092 +/- 0.020 L/kg [P < .05] and 0.110 +/- 0.018 L/kg versus 0.172 +/- 0.046 L/kg [difference not statistically significant], respectively). The mean residence time was similar in both groups (0.77 +/- 0.06 hours versus 0.65 +/- 0.14 hours [difference not statistically significant]).

Conclusions: A reduction in the total serum clearance and a decrease in the initial volume of distribution of lanreotide were observed in patients with severe chronic renal insufficiency treated with one intravenous bolus dose of 7 microg/kg lanreotide.