Details

Autor(en) / Beteiligte

• Comets, E.
• Mentré, F.
• Nimmerfall, F.
• Kawai, R.
• Mueller, I.
• Marbach, P.
• Vonderscher, J.

Titel

Nonparametric analysis of the absorption profile of octreotide in rabbits from long-acting release formulation OncoLAR

Ist Teil von

• Journal of controlled release, 1999-05, Vol.59 (2), p.197-205

Ort / Verlag

Amsterdam: Elsevier B.V

Erscheinungsjahr

1999

Quelle

Elsevier Journal Backfiles on ScienceDirect (DFG Nationallizenzen)

Beschreibungen/Notizen

• Octreotide (octreotide-acetate, Sandostatin®) is a somatostatin analogue, used in long-term treatment of acromegaly. The present study describes the absorption profile in rabbits of octreotide after release from the long-acting formulation OncoLAR (denoted as octreotide-LAR). In a first experiment, the disposition kinetics of octreotide was studied for 24 h in six rabbits after intravenous (i.v.) injection of 0.025 mg of a solution of octreotide. In a second experiment, release kinetics was studied in eight rabbits for 49 days after an i.m. injection of 5 mg/kg of octreotide-LAR. Concentrations were determined by radioimmunoassay. After i.v. injection of octreotide, one- and two-compartment models were compared for each rabbit. A typical disposition profile was computed using the mean parameters. After i.m. injection of octreotide-LAR, deconvolution was performed using the point-area method. Individual absorption profiles were characterised using natural splines. The number of breakpoints was selected using the generalised cross-validation criterion. The two compartment model was selected based on the i.v. study. After i.m. administration, octreotide exhibited a triphasic absorption profile, with large interindividual variability. A transient peak followed the initial burst phase. The third phase covered 85% of total drug released. The approach allows a model-independent description of the in vivo absorption profile of octreotide-LAR.