Endocrine Abstracts (2003) 6 P47

Lanreotide Autogel in acromegaly: a pharmacokinetic and pharmacodynamic analysis

JM Cendros1, C Peraire1, I Troconiz2 & R Obach1

1Ipsen Pharma S.A., Sant Feliu de Llobregat, Barcelona, Spain; 2University of Navarra, Navarra, Spain.

Autogel is a long-acting formulation of the somatostatin analogue lanreotide, and is effective against the symptoms of acromegaly when given by monthly deep s.c. injection. This open, Phase III, multicentre study assessed the pharmacokinetic (PK) and population PK/pharmacodynamic profile of lanreotide Autogel in patients with acromegaly who had previously received the prolonged-release (PR) formulation of lanreotide, 30mg microparticle depot formulation, given i.m.

Lanreotide Autogel was given s.c. every 28 days for 60 weeks at a dose of 60, 90 or 120mg. Dose titrations could occur at weeks 16, 32, 48 according to biochemical efficacy, as determined by patients' growth hormone (GH) and insulin-like growth factor (IGF-1) response. Serum GH and lanreotide levels were measured at baseline and immediately before injections at weeks 4, 12, 28, 44, 60.

A total of 130 patients received lanreotide Autogel and 117 reached steady state with at least one dose level and were included in the PK analysis. The mean (plus/minus SD) minimum serum levels of lanreotide at steady state were 1.949 plus/minus 0.619 (n=60), 2.685 plus/minus 0.783 (n=56) and 3.575 plus/minus 1.271ng/mL (n=53) in the 60, 90, 120mg dose groups, respectively. The equivalent values for the 10 patients who reached steady state at all three dose levels were 1.602 plus/minus 0.628, 2.349 plus/minus 0.701 and 3.650 plus/minus 1.668ng/mL at 60, 90 and 120mg, respectively. Dose-proportional PK behaviour was observed from the comparison at all three dose levels. The relationship between lanreotide and GH serum concentration could be described by a simple inhibitory Emax model that allowed for the incomplete inhibition of GH. The maximum effect (Emax) resulted in a maximum reduction in GH of 82% with a low relative standard error of plus/minus 7.53%, and a concentration of lanreotide of 0.206ng/mL (EC50) was associated with a 50% reduction in mean GH values.

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