Leuprolide

Leuprolide is a synthetic nonapeptide used to treat both endometriosis in women and prostate cancer in men. 

Leuprolide, structure of, 1056 I.evorotatory, 295 Lewis, Gilbert Newton. 8 Lewis acid, 57-58 examples of, 58 reactions of, 57-58 Lewis base, 57, 59-60 examples of, 59 reactions of, 59-60 Lewis structure, 9 resonance and, 43 Lexan, structure and uses of, 819,... 

Bicalutamide may increase the effect of oral anticoagulants. Flutamide enhances the action of leuprolide. Additive antineoplastic effects may occur when leuprolide is administered with megestrol or flutamide. Estrogens decrease the effectiveness of tamoxifen. 

Ogawa, Y., Yamamoto, M., Takada, S., Okada, H., and Shimamoto, T., Controlled-release of leuprolide acetate from... 

Leuprolide 3.75 mg intramuscularly26 Hot flashes, night sweats, headache, nausea... 

If treatment with an SSRI or another antidepressant such as clomipramine is not successful, hormonal treatment with a GnRH agonist, such as leuprolide, maybe considered. The use of leuprolide improves premenstrual emotional symptoms as well as some physical symptoms such as bloating and breast tenderness. Cost, the need for intramuscular administration, and the side effects of hypoestrogenism (e.g., vaginal dryness and hot flashes) limit its use. 

Eating disorders leuprolide acetate, nafarelin, gosarelin)... 

Pseudoephedrine dosed at 30 to 60 mg/day taken at bedtime has been used to prevent or decrease the number of episodes of priapism.6 Terbutaline 5 mg has been used orally to prevent priapism with mixed results.38,39 Leuprolide, a gonadotropinreleasing hormone, also has been used for this indication. Hydroxyurea may be helpful in some patients. The use of antiandrogens is under investigation.6,27... 

LHRH Analogs Goserelin Leuprolide Triptorelin 3.6 mg SC every 28 days 7.5 mg IM every 28 days 3.75 mg IM every 28 days Hot flashes, amenorrhea, menopausal symptoms, injection site reactions... 

Several randomized trials have demonstrated that leuprolide and goserelin are effective agents when used alone in patients with advanced prostate cancer.19 Response rates around 80% have been reported, with a lower incidence of adverse effects compared with estrogens.19 There are no direct comparative trials of the currently available LHRH agonists or the dosage formulations, but a recent meta-analysis reported that there is no difference in efficacy or toxicity between leuprolide and goserelin. Therefore, the choice between the two usually is made based on cost and patient and physician preference for a dosing schedule. 

Combining an LHRH agonist with flutamide demonstrated response rates greater than 90% in previously untreated patient, and the median survival was 61 months in the combination arm and 41 months in the leuprolide-alone arm in patients with minimal disease.38 However, in a comparison of goserelin with goserelin and flutamide conducted in 589 patients with 10 years of follow-up, combined androgen blockade (CAB) showed no benefit over goserelin alone.39... 

A number of other peptide molecules are currently being explored for delivery via inhalation (6). Very recently, a much smaller peptide (leuprolide, about 9 amino acid residues) has been delivered by metered dose inhaler (MDI) in a characterized fashion to humans (7). This work revealed that about 50% of a dose deposited in the lung could be bioavailable. This value is much greater than those reported for nasal bioavailabilities of this and similar molecules (8). These results, and ours in the rat lung (9), imply that inhalation administration of some peptide and polypeptide molecules is perfectly feasible. 

The systemic delivery of drugs was pioneered with a pMDI product, leuprolide acetate, for the treatment of prostate cancer. A considerable amount of work was conducted to demonstrate feasibility of delivery of this... 

Sanz-Nebot, V., Benavente, F., Barbosa, J. (2002). Liquid chromatography-mass spectrometry and capillary electrophoresis combined approach for separation and characterization of multicomponent peptide mixtures application to crude products of leuprolide synthesis. J. Chromatogr. A 950, 99-111. 

Leuprolide -LHRH agonist -endocrine effects -hot flashes -decreased libido -gynecomastia (3%) -breast tenderness -impotence (2%) -nausea and vomiting (uncommon) -transient increase in bone pain -peripheral edema -dizziness, headache... 

Leuprolide 3.75 mg IM every 28 days injection site reactions (extended formulations... 

Ovarian ablation (oophorectomy) is considered by some to be the endocrine therapy of choice in premenopausal women and produces similar overall response rates as tamoxifen. Medical castration with an LHRH analog, goserelin, leuprolide, or triptorelin, is a reversible alternative to surgery. 

There are no comparative trials of LHRH agonists, so the choice is usually based on cost (Table 65-1) and on patient and physician preference. Leuprolide acetate is administered daily. Leuprolide depot and goserelin acetate implant can be administered monthly, or every 12 or 16 weeks. 

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