GHRP6, (GnRH) which displays significantly greater biological activity compared to the natural peptide. This is because it has an increased affinity for GnRH receptors and a prolonged or lengthened half-life as a result of its resistance to enzymatic degradation.
Triptorelin is a GnRH agonist as it inhibits the release of gonadotropin when given over a sustained period of time in therapeutic doses. animal studies have shown that the administration of triptorelin results in an initial but short-lasting increase in the levels of lutenizing hormone (LH), testosterone as well as the follicle stimulating hormone (FSH). In 14-day oestrus suppression analysis in rats, triptorelin exhibited 100 times greater potency compared to the natural gonadotropin-releasing hormone.
In preclinical studies commissioned to establish the effective doses, a single dose of 100 g injected in mice via the vaginal canal resulted in a increase in LH levels which peaked 3 hours later. When assessed 24 hours later, the levels of LH in the blood had decreased considerably and from 30-35 hrs, had returned to the pre-dose levels in all the animals.
Secondary pharmacodynamical effects are expected following the sustained parenteral administration due to pituitary desensitization. The consequent gonadal suppression and decrease in serum sex steroids was corroborated by use in human medicine.
Due to the similarities (GnRH), the pharmacokinetics activities of triptorelin are very comparable to those of GnRH. This was confirmed by data which revealed that there was a triphasic decline in plasma in mice. There was also a very significant volume of distribution to the tissues and degradation into inactive components by peptidases, majorly in the kidneys and liver, but also in some other tissues like the pituitary. These patterns of distribution were generally similar for all the GnRH analogues.
When it comes to differences in pharmacokinetics, triptorelin does have a longer half-life than GnRH, and a substantial amount of the parenteral dose was excreted in urine as unaltered peptide. This is due to the single amino acid substitution, D-tryptophan6 rather than glycine6, which results in enhanced protection from degradation by peptidases. This is also the reason for the high affinity for pituitary receptors.
Target animal safety studies have shown that Triptorelin is safe when intravaginal administration was done. Similarly, oral doses did not produce any major biological or toxicological effects, whether it is on LH levels, oestrus cycling or in any other microscopic changes. Over a period of 45 days, repeat doses of up to 4 g/kg bw were administered orally to rats, the result being no increases in LH levels were observed at the beginning and end of the observation period. On the 14th day, a single injection of 400 g was administered under the skin, before the oral dose was given. The effects induced were similar to the known pharmacological effects that have been documented, such as a decrease in the testosterone levels in male mice and loss of spermatogenesis. The effect in female rats was a decrease in progesterone and the ultimate cessation of the oestrus cycle.
Continuous long-term exposure of Triptorelin through the parenteral route can have toxic effects on reproduction. Due to the low availability, oral administration is not expected to affect reproduction.