Nafarelin acetate is rapidly absorbed into the systemic circulation after intranasal administration. Maximum serum concentrations (measured by RIA) were achieved between 10 and 40 minutes. Following a single dose of 200 µg base, the observed average peak concentration was ng/mL (range to ng/mL), whereas following a single dose of 400 µg base, the observed average peak concentration was ng/mL (range to ng/mL). Bioavailability from a 400 µg dose averaged % (range to %). The average serum half-life of nafarelin following intranasal administration is approximately 3 hours. About 80% of nafarelin acetate is bound to plasma proteins at 4°C. Twice daily intranasal administration of 200 or 400 µg of Synarel in 18 healthy women for 22 days did not lead to significant accumulation of the drug. Based on the mean C min levels on Days 15 and 22, there appeared to be dose proportionality across the two dose levels.
The research in my laboratory has made significant contributions in the field of Comparative Immunoendocrinology and Reproductive Physiology using reptiles and fish as animal models. In recent years, we have explored the neuroendocrine control of non-specific immune responses in fish, Channa punctatus, and wall lizards, Hemidactylus flaviviridis. For the first time we demonstrated sexual dimorphism in immune responses in reptiles. Genomic action of catecholamines in regulation of phagocytosis in wall lizards, and non-genomic action of cortisol in fish are the novel observations from our laboratory.
In the area of reproductive physiology in reptiles, our research was among the first to demonstrate regional histological and functional differentiation in the epididymis. Further, our work has established the cross-talk between Leydig cell-Sertoli cell, Leydig cell-testicular macrophage and Leydig cell-mast cell in wall lizards. We have reported that reptilian folliculogenesis, spermatogenesis and steroidogenesis are regulated exclusively by FSH, in contrast to mammals. Presently, we are studying the differential expression of genes regulating gonadal cyclicity in fish and lizards. Also, an effort is being made to demonstrate the temporal expression of specific gonadotropin and sex steroid receptors in both the model organisms. Apart from this, the immunological study in fish and lizards is aimed to study the toll-like receptors and their defensive role in the animal.