Pharmacokinetic and endocrinological parameters of a slow-release depot preparation of the GnRH analogue ICI 118630 (Zoladex) compared with a subcutaneous bolus and continuous subcutaneous infusion of the same drug in patients with prostatic cancer

Seventeen patients with advanced prostatic cancer were treated with the gonadotrophin-releasing hormone analogue DSer (tBU)6 AzaGly10 GnRH (ICI 118630), either as a constant SC infusion, or in the form of a monthly SC slowrelease depot formulation, in which case patients were randomised to receive one of three doses. Six of these patients also received a 250-μg SC bolus of ICI 118630, for pharmacokinetic studies, before starting the infusion or the depot. Drug levels were measured using a bouble-antibody radioimmunoassay. In contrast to the SC infusion, which gave a smooth serum 118630 level profile, drug release from the depot preparation was not constant, levels varying in a predictable manner throughout each 28-day period, reaching a peak proportional to the dose of ICI 118630 received, between days 15 and 18 of each cycle. With all methods of administration there was an initial rise in LH, usually followed by a rise in testosterone, after which the SC infusion and the depot were both effective in reducing serum LH to basal levels and testosterone into the castrate range within 1 month.