FDA RECOMMENDATIONS FOR PRECLINICAL TESTING OF GONADOTROPIN-RELEASING-HORMONE (GNRH) ANALOGS

Gonadotropin-releasing hormone (GnRH) agonists and antagonists are syn thetic analogues synthesized by modifications of the naturally occurri ng hypothalamic decapeptide GnRH. These modifications significantly in crease the biological potency and duration of action of GnRH agonists as well as the solubility, potency, and duration of action of GnRH ant agonists while decreasing GnRH antagonists toxicity. The field of GnRH analogues has expanded significantly during the past few years in ter ms of the number of analogues, therapeutic indications, formulations, and mode of administration. This paper provides recommendations for no nclinical testing of GnRH analogues and reflects the type and degree o f toxicity testing expected by the Division. However, these recommenda tions are not formal guidelines in that alternative testing methods wi ll be considered. Furthermore, these recommendations should not be use d as guidance for testing of other new drugs. (C) 1994 Academic Press, Inc.