title: A radioimmunoassay for GnRH agonist analogue in serum of patients with prostate cancer treated with D-Ser (tBu)6 AZA Gly10 GnRH.
abstract: A radioimmunoassay is described for D-Ser (tBu)6 AZA Gly10 GnRH (ICI 118630) in serum of prostate cancer patients treated chronically with this peptide to produce a medical castration. With 125I-118630 as the label, and an anti-GnRH serum, the specificity of the assay is directed to the N-terminal end of the peptide, and putative degradation products have less than 6% cross-reactivity. The assay appears specific for intact 118630 which, after subcutaneous administration of 250 micrograms, has a half-time of disappearance from the serum of 4.9 +/- 0.4 h and a volume of distribution of 13.7 +/- 0.8 litres. Continuous subcutaneous infusion of 120 micrograms 118630/d gave stable serum concentrations of between 2-3 ng/ml for up to 63 d which were very similar to values predicted from pharmacokinetic analysis of the analogue clearance rate. This contrasts with the "peak and trough' pattern of serum 118630 levels measured in two subjects after 118630 administration from a subcutaneous implant containing 3.6 mg of peptide in a biodegradable formulation. Serum 118630 levels peaked at between 6-8 ng/ml 15 d after the implant and fell to less than 1 ng/ml at 29 d, immediately before the next implant. Serum 118630 levels following a second 3.6 mg implant were almost identical with respect to absolute concentration and time to peak value as after the first implant. This assay will be of value not only for evaluation of the pharmacokinetics of GnRH analogue release from new long-acting formulations, but also for correlation of serum peptide concentrations with pituitary gonadotroph desensitization.
authors.forename: R N
authors.initials: RN
authors.lastname: Clayton
authors.forename: L C
authors.initials: LC
authors.lastname: Bailey
authors.forename: J
authors.initials: J
authors.lastname: Cottam
authors.forename: D
authors.initials: D
authors.lastname: Arkell
authors.forename: T J
authors.initials: TJ
authors.lastname: Perren
authors.forename: G R
authors.initials: GR
authors.lastname: Blackledge
mesh_terms: D002064:Buserelin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood; D003692:Delayed-Action Preparations; D004343:Drug Implants; D017273:Goserelin; D006801:Humans; D007263:Infusions, Parenteral; D007700:Kinetics; D008297:Male; D011471:Prostatic Neoplasms / Q000097:blood* / Q000188:drug therapy; D011863:Radioimmunoassay / Q000379:methods
chemical_list: D003692:Delayed-Action Preparations; D004343:Drug Implants; D017273:Goserelin; D002064:Buserelin