Nafarelin Tablet

Endometriosis is a common benign gynecological disease in women of childbearing age, with an incidence rate of approximately 1/15 and a prevalence of 10%–15% among reproductive-age females. Its main clinical manifestations include pelvic pain, dysmenorrhea, dyspareunia, chronic pelvic pain and infertility, which severely impair patients' physical and mental health as well as quality of life. The pathogenesis is closely correlated with estrogen levels; the growth, proliferation and infiltration of ectopic endometrial lesions rely on persistent estrogen stimulation. Lesions may invade multiple sites such as the pelvic peritoneum, ovaries and fallopian tubes, triggering complications including adhesions and cysts.

As a synthetic GnRH agonist, nafarelin tablet continuously and efficiently activates pituitary GnRH receptors to induce desensitization, thereby strongly suppressing the secretion of pituitary gonadotropins (luteinizing hormone and follicle-stimulating hormone). This leads to a significant decline in endogenous estrogen levels, depriving ectopic endometrial lesions of hormonal support and causing gradual atrophy and regression. It effectively relieves various painful symptoms, reduces lesion size and improves pelvic adhesions, without compromising subsequent fertility recovery. The pregnancy rate after treatment is comparable to that of the traditional drug danazol.

In assisted reproductive technologies such as In Vitro Fertilization and Embryo Transfer (IVF-ET) and Intracytoplasmic Sperm Injection (ICSI), down-regulation is a key step in ovulation induction therapy. Its core goal is to suppress spontaneous pituitary gonadotropin secretion, avoid premature follicle maturation, achieve precise regulation of follicular development, and improve ovulation induction efficacy and oocyte quality.

With its stable GnRH agonistic effect, it is one of the commonly used drugs for down-regulation in assisted reproduction.

By persistently inhibiting pituitary gonadotropin secretion, it effectively prevents the premature luteinizing hormone (LH) surge and premature ovulation, ensures synchronous development of multiple follicles, increases the number of high-quality follicles and elevates oocyte retrieval rate.Meanwhile, its stable and reliable down-regulatory effect effectively reduces cycle cancellation rates caused by asynchronous follicular development and premature ovulation.

It exerts no obvious adverse impacts on oocyte quality and embryo implantation potential, significantly improving embryo implantation rate and clinical pregnancy rate, and optimizing overall assisted reproductive treatment outcomes.

In addition, its oral administration route is more convenient compared with injectable down-regulatory agents, effectively alleviating injection pain and improving medication compliance, especially suitable for patients with injection phobia or poor treatment adherence.

Moreover, it can serve as an adjuvant therapy for benign prostatic hyperplasia in males. The occurrence of benign prostatic hyperplasia is closely associated with testosterone levels. By lowering testosterone concentration, it inhibits abnormal prostatic tissue hyperplasia and alleviates lower urinary tract symptoms including frequent micturition, urgent micturition, dysuria and nocturia, improving patients' voiding function and quality of life. However, its current clinical application is relatively limited, mostly used as a second-line regimen when surgical treatment or first-line medications yield unsatisfactory outcomes.

Furthermore, multiple clinical studies have demonstrated that nafarelin tablet can be used for palliative treatment of certain hormone-dependent tumors (e.g., endometrial cancer and prostate cancer). By potently suppressing sex hormone secretion, it effectively delays tumor cell growth and metastasis, alleviates tumor-related symptoms, enhances patients' quality of life, prolongs survival time, and provides a new therapeutic option for patients with advanced hormone-dependent tumors.

Absorption

After oral administration, it is absorbed via the gastrointestinal tract. As a peptide compound, it is easily degraded by gastrointestinal peptidases, resulting in relatively low bioavailability, with an average of 2.8%–8% and a range of 1.2%–5.6%. The drug is absorbed rapidly, reaching peak plasma concentration (Cmax) within 10–40 minutes after oral intake, and Cmax is positively correlated with administered dose. A single oral dose of 0.2 mg yields a Cmax of approximately 0.6 ng/mL, while a single 0.4 mg dose results in a Cmax of about 1.8 ng/mL. Food has minimal impact on its absorption, and the drug can be taken before or after meals; however, fixed dosing time is recommended to maintain stable plasma drug concentration.

Notably, gastrointestinal diseases (such as gastritis, gastric ulcer, enteritis, etc.) may impair drug absorption and further reduce bioavailability, requiring dose adjustment under medical supervision.

Distribution

After entering the blood circulation, it is rapidly distributed to various tissues and organs throughout the body, with relatively high concentrations in target organs including the pituitary and gonads, which is closely related to its pharmacological targets. Its plasma protein binding rate is approximately 80% (at 4 ℃), mainly binding to plasma albumin; the protein-bound form is pharmacologically inactive, while the free form exerts therapeutic effects.

The drug can cross the blood-brain barrier and distribute slightly in brain tissue at low concentrations, causing no obvious adverse effects on the central nervous system. Additionally, a small amount of the drug is secreted into breast milk, hence it is contraindicated in lactating women.

Metabolism

It is mainly metabolized by peptidases rather than the cytochrome P450 enzyme system, leading to fewer drug interactions with other agents metabolized via cytochrome P450. Its major metabolites include short peptide fragments, naphthylalanine and 2-naphthoacetic acid, all of which are pharmacologically inactive with no additional pharmacological effects.

After subcutaneous injection in males, the half-life of metabolites is approximately 85.5 hours; after oral administration, the half-life of the parent drug and metabolites is about 2.5–3.0 hours, slightly shorter than intranasal administration (half-life: 3–4 hours), which is associated with the low oral bioavailability. In healthy women taking 0.2 mg or 0.4 mg twice daily for 22 consecutive days, no obvious drug accumulation is observed, indicating high safety of long-term administration at conventional doses.

Excretion

The product and its metabolites are mainly excreted via the kidneys and intestines. Among the administered dose, 44%–55% is excreted in urine, with the unchanged parent drug accounting for only about 3% of urinary excretion and the rest being metabolites; 18.5%–44.2% is excreted in feces with a relatively slow excretion rate.

After a single dose, the drug and its metabolites persist in the body for a certain period to ensure long-acting efficacy. In patients with renal insufficiency, reduced urinary excretion capacity may cause accumulation of the drug and metabolites, requiring appropriate dose reduction. In patients with hepatic insufficiency, impaired metabolic enzyme activity also necessitates dose adjustment under medical supervision to avoid aggravated adverse reactions.