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

J Control Release. 1999 May 20;59(2):197-205. doi: 10.1016/s0168-3659(98)00194-1.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorption
  • Animals
  • Delayed-Action Preparations / pharmacokinetics*
  • Hormones / pharmacokinetics*
  • Infusions, Intravenous
  • Injections, Intramuscular
  • Male
  • Octreotide / pharmacokinetics*
  • Rabbits
  • Regression Analysis
  • Reproducibility of Results

Substances

  • Delayed-Action Preparations
  • Hormones
  • Octreotide