STUDIES ON SUSTAINED CONTRACEPTIVE EFFECTS WITH SUBCUTANEOUS POLYDIMETHYLSILOXANE IMPLANTS

Abstract

ABSTRACT Diffusion of [14C] megestrol acetate from polydimethylsiloxane (PDS) implants was studied in ten human volunteers during a period of one year. In vitro diffusion rates for each capsule were measured in 100 ml of distilled water changed every 24 hours, until constant diffusion was reached. After insertion of 3 capsules in the subcutaneous tissue of the left arm, approximately 60 to 70 per cent of the total radioactivity excreted daily was present in the urine. Throughout the experiment, diffusion was calculated on the basis of total urinary radioactive metabolites excreted daily. At the beginning of the experiment, the faecal plus urinary radioactivity recovered approached the values obtained under in vitro conditions. However, on subsequent days, a rapid decrease in the diffusion of megestrol acetate from the implants was noticed. Two months after insertion of the capsules, the daily diffusion was decreased to approximately 50 per cent of the initial values. After the third month, the excretion of urinary metabolites, and therefore the diffusion from the implants, becomes more uniform and stable; from the fourth month onwards the release can be considered as practically constant up to one year. Nine out of ten volunteers behaved in the same way; the tenth subject showed the same excretion pattern but the absolute excretion values were significantly (P < 0.01) lower than the average. It is concluded that the in vitro incubation is a reliable way of calculating the in vivo diffusion from PDS capsules inserted in the human, although, for all practical purposes, effective levels attained in the body will be only half of this value. With this important limitation diffusion in the human of megestrol acetate embedded in PDS, can be considered to be constant.