Evaluation of the releasing pharmacokinetics of depot preparations of Leuprolide

DIDIER, C.; OGGERO EBERHARDT, M.; KRATJE, R. B.; ETCHEVERRIGARAY, M.

Transport Phenomena and Unit Operations ? Food Sience and Engineering Biotechnology

Centro de Publicaciones CERIDE-CONICET

Lugar: Santa Fe; Año: 2001 vol. 3 p. 1753 - 1758

1666-1621

Leuprolide is a synthetic nonapeptide analogue of the naturally occuring Luteinizing Hormone Releasing Hormone (LH RH) that exerts high gonadothropin releasing and ovulation inducing activities. The continuous administration of therapeutic doses of leuprolide inhibits the growth of certain hormone dependent prostatic and mammary tumors.The aim of this work was to investigate the pharmacokinectic behaviour of leuprolide acetate from a controlled release parenteral dosage form in rats. A radioimmunoassay to quantify the analogue has been developed using a polyclonal antiserum obtained in our lab from rabbits immunized with peptide-protein conjugates. The RIA was linear in the range between 1 ng/ml and 62.5 ng/ml with a detection limit of 100 pg, resulting in a sensitive and reliable technique to evaluate the releasing kinetic of depot preparations. Two samples containing PLGA-microcapsules were tested: the commercial preparation was considered as a reference. Wistar rats were innoculated subcutaneously (1.25 mg/rat) and bled by vein puncture at different times: 1, 4 , 12 hours and 1, 3, 7, 14, 21, 28 and 35 days post-injection. Statistical treatment consisted of an analysis of variance (ANOVA) in one way for the case of subsampling and non-orthogonal comparisons between the reference and the samples. The releasing kinetic of the drug was established. After a single injection of the microcapsules, an initial burst of the analogue, followed by a plateau level for 4 weeks was determined. No significant differences between the standard reference and the sample were observed. [Participants of the 3rd Mercosur Congress on Process Systems Engineering (ENPROMER) were invited to present a full paper, which was published in ?Transport Phenomena and Unit Operations ? Food Sience and Engineering Biotechnology?, ISSN 1666-1621, Centro de Publicaciones CERIDE-CONICET, Santa Fe (2001) Vol. III, p. 1753 -1758].