Leuprolide dosing

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... 

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. 

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. 

Uterine leiomyomata are benign, estrogen-sensitive, fibrous growths in the uterus that can cause menorrhagia, with associated anemia and pelvic pain. Treatment for 3-6 months with a GnRH agonist reduces fibroid size and, when combined with supplemental iron, improves anemia. Leuprolide, goserelin, and nafarelin are approved for this indication. The doses and routes of administration are similar to those described for treatment of endometriosis. 

Treatment can be carried out with injections of leuprolide or nasal application of nafarelin. Leuprolide treatment is usually initiated at a dosage of 0.05 mg/kg body weight injected subcutaneously daily and then adjusted on the basis of the clinical response. Pediatric depot preparations of leuprolide are also available. The recommended initial dosage of nafarelin for central precocious puberty is 1.6 mg/d. This is achieved with two-unit dose sprays (each spray contains 0.1 mL, 0.2 mg) into each nostril twice daily. Treatment with a GnRH agonist is generally continued to age 11 in females and age 12 in males. 

Zheng, J. Y., Fulu, M. Y., Lee, D. Y., Barber, T. E., and Adjei, A. L. (2001), Pulmonary peptide delivery Effect of taste-masking excipients on leuprolide suspension metered-dose inhalers, Pharm. Dev. Technol., 6,521-530. 

Modalities to prevent priapism are limited and not well studied. Pseudoephedrine (30 or 60 mg/day given orally at bedtime) and leuprolide, a gonadotropin-releasing hormone, have been used to decrease the number of recurrent episodes of priapism. Hydroxyurea therapy may also be useful. Recently, low-doses of an antiandrogen, bicalutamide, have been used in two patients with SCD and one patient with spinal cord injury for treatment of recurrent and refractory priapism without major side effects. " " ... 

Figure 9.4 Plasma concentrations of leuprolide acetate (C eupro) following single oral administration of leuprolide saline solution and microemulsion at a dose of 3 mg kg-1 in rats (n = 5 mean SD) as a function of the time after administration (tadmm). The leuprolide acetate microemulsion was superior to that of saline solution. (Figure redrawn with data from Ref. [1 06], reprinted with permission of Elsevier.)...

C) In steady doses, leuprolide inhibits the release of pituitary gonadotropins... 

Mericq V, Lammoglia JJ, Unanue N, Villaroel C, Hernandez MI, Avila A, Ifiiguez G, Klein KO. Comparison of three doses of leuprolide acetate in the treatment of central precocious puberty preliminary results. Clin Endocrinol (Oxf) 2009 71(5) 686-90. 

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