title: Nonparametric analysis of the absorption profile of octreotide in rabbits from long-acting release formulation OncoLAR.
abstract: Octreotide (octreotide-acetate, Sandostatin(R)) 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.
authors.affiliation: Inserm U 436, CHU Pitié-Salpêtrière, 91 Bd de l'Hôpital, 75-013 Paris, France. eco@biomath.jussieu.fr
authors.forename: E
authors.initials: E
authors.lastname: Comets
authors.forename: F
authors.initials: F
authors.lastname: Mentré
authors.forename: F
authors.initials: F
authors.lastname: Nimmerfall
authors.forename: R
authors.initials: R
authors.lastname: Kawai
authors.forename: I
authors.initials: I
authors.lastname: Mueller
authors.forename: P
authors.initials: P
authors.lastname: Marbach
authors.forename: J
authors.initials: J
authors.lastname: Vonderscher
mesh_terms: D000042:Absorption; D000818:Animals; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics*; D006728:Hormones / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D007273:Injections, Intramuscular; D008297:Male; D015282:Octreotide / Q000493:pharmacokinetics*; D011817:Rabbits; D012044:Regression Analysis; D015203:Reproducibility of Results
chemical_list: D003692:Delayed-Action Preparations; D006728:Hormones; D015282:Octreotide