PMID- 2110458
OWN - NLM
STAT- MEDLINE
DCOM- 19900604
LR  - 20130529
IS  - 0004-4172 (Print)
IS  - 0004-4172 (Linking)
VI  - 40
IP  - 2 Pt 1
DP  - 1990 Feb
TI  - Development of radioimmunoassay for a potent luteinizing hormone-releasing 
      hormone antagonist. Evaluation of serum levels after injection of 
      [Ac-3-(2-naphthyl)-D-Ala1, D-Phe(pCl)2, 3-(3-pyridyl)-D-Ala3, D-Cit6, D-Ala10] 
      LHRH.
PG  - 111-8
AB  - Highly potent antagonistic analogs of luteinizing hormone-releasing hormone 
      (LHRH), free of edematogenic effects have been developed. These analogs proved to 
      be potent inhibitors of LH, follicle stimulating hormone (FSH) and sex steroid 
      levels in animals and human beings. The clinical utility of these compounds would 
      be greatly enhanced by a sustained delivery system, capable of maintaining 
      therapeutic peptide levels in blood over an extended period of time. 
      Consequently, long acting formulations of microcapsules were prepared from one of 
      the most potent antagonists, [Ac-3-(2-naphthyl)-D-Ala1, D-Phe (pCl)2, 
      3-(3-pyridyl)-D-Ala3, D-Cit6, D-Ala10] LHRH (SB-75). The microcapsules consisted 
      of 2% w/w SB-75 in poly-DL-lactide-co-glycolide (PLGA), a biocompatible, 
      biodegradable polymer. To facilitate pharmacokinetic studies necessary for 
      experimental and clinical investigation of the microencapsulated analog, a highly 
      sensitive and specific radioimmunoassay was developed. The antibody against SB-75 
      was generated in rabbits. No significant cross-reaction could be detected with 
      several natural peptides and analogs tested. The sensitivity of the assay is 0.6 
      pg/tube. The RIA is suitable for direct determination of SB-75 level in 20 
      microliters serum. The two lots of SB-75 microcapsules exhibited different 
      pharmacokinetic release patterns. Single intramuscular injection of 20 mg SB-75 
      microcapsules, PLGA batch No. 001, into female rats maintained elevated serum 
      SB-75 levels for three weeks. The suppression of LH secretion during this period 
      was indicated by histological findings. The ovaries in the treated group were 
      polyfollicular and no corpora lutea were present, indicating a prolonged ovarian 
      inactivity due to LH deprivation.(ABSTRACT TRUNCATED AT 250 WORDS)
FAU - Csernus, V J
AU  - Csernus VJ
AD  - Endocrine Polypeptide and Cancer Institute, V.A. Medical Center, New Orleans, LA.
FAU - Szende, B
AU  - Szende B
FAU - Groot, K
AU  - Groot K
FAU - Redding, T W
AU  - Redding TW
FAU - Schally, A V
AU  - Schally AV
LA  - eng
GR  - CA 40003/CA/NCI NIH HHS/United States
GR  - CA 40004/CA/NCI NIH HHS/United States
GR  - CA 40077/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Germany
TA  - Arzneimittelforschung
JT  - Arzneimittel-Forschung
JID - 0372660
RN  - 0 (Capsules)
RN  - 0 (Pituitary Hormones)
RN  - 0 (Serum Albumin, Radio-Iodinated)
RN  - 33515-09-2 (Gonadotropin-Releasing Hormone)
RN  - 9002-68-0 (Follicle Stimulating Hormone)
RN  - OON1HFZ4BA (cetrorelix)
SB  - IM
MH  - Animals
MH  - Capsules
MH  - Female
MH  - Follicle Stimulating Hormone/blood
MH  - Gonadotropin-Releasing Hormone/*analogs & derivatives/*antagonists & 
      inhibitors/blood
MH  - Immunohistochemistry
MH  - Male
MH  - Pituitary Hormones/blood
MH  - Radioimmunoassay
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Serum Albumin, Radio-Iodinated
EDAT- 1990/02/01 00:00
MHDA- 1990/02/01 00:01
CRDT- 1990/02/01 00:00
PHST- 1990/02/01 00:00 [pubmed]
PHST- 1990/02/01 00:01 [medline]
PHST- 1990/02/01 00:00 [entrez]
PST - ppublish
SO  - Arzneimittelforschung. 1990 Feb;40(2 Pt 1):111-8.