Ovarian Cysts Research Today is a free monthly online journal that collates and summarizes the latest research about Ovarian Cysts, including details on causes, treatment, symptoms, infertility.

A preclinical pharmacokinetic/pharmacodynamic approach to determine a dose of GnRH, for treatment of ovarian follicular cyst in cattle.

Monnoyer S, Guyonnet J, Toutain PL

CEVA Santé Animale, Preclinical Department, Z.I. La Ballastière, Libourne cedex, France.

The objective of this study was to explore the value of a preclinical PK/PD approach to determine a gonadotropin-releasing hormone (GnRH) dose in cows using the pituitary LH response as a surrogate endpoint. Using an indirect effect model with stimulation of the LH entry rate, the in vivo basic pharmacodynamic parameters of GnRH were determined. The EC(50) of GnRH was 51 +/- 16 pg/mL, the EC(50) being the GnRH plasma concentration able to produce 50% of the maximum possible stimulation (S(max)) of the hypophysis (S(max) = 48 +/- 13). From individual PK/PD parameters, the ED(50) of GnRH, i.e. the estimated dose of GnRH required to determine half the maximum possible stimulating effect on LH release, was calculated to 62 microg/h per cow. Using the PK/PD model, the GnRH dose required to achieve a selected breakpoint value of 5 ng/mL for maximum LH concentration (surrogate value for LH concentration predicting clinical efficacy for cystic conditions), was 52 +/- 18 microg and for a standard GnRH dose of 100 microg, the mean maximum plasma LH concentration predicted by the model was 7.22 +/- 0.98 ng/mL.

Published 16 December 2004 in J Vet Pharmacol Ther, 27(6): 527-35.
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