Buserelin

Gonadotropin releasing hormone analogs (goserelin, buserelin, leuprorelin, triptorelin) inhibit gonadotropin release and thus lower testosterone or estrogen levels. They are used to treat breast cancer and prostate cancer. 

K. Abe, T. Irie, and K. Uekama. Enhanced nasal delivery of luteinizing hormone releasing hormone agonist buserelin by oleic acid solubilized and stabilized in hydroxypropyl-/S-cyclodextrin. Chem Pharm Bull 43 2232-2237 (1995). 

In recent studies both in vitro (Caco-2 cells) and in vivo in rats, TMC with a degree of trimethylation of 60% was proven to be an excellent intestinal absorption enhancer of the peptide drugs buserelin and octreotide. The observed absolute bioavailability values were 13 and 16% for buserelin and octreotide, respectively [83] (impublished data Fig. 5). Permeation enhancing effects were more responsible for these increased bioavailabilities, rather than the mucoadhesive properties of the TMC polymers. Nevertheless, mucoadhesion is a prerequisite for these polymers in order to further act as absorption enhancers. 

LueBen, H.L., De Leeuw, B.J., Langemeyer, M.W., De Boer, A.G., Verhoef, J.C., and Junginger, H.E., Mucoadhesive polymers in peroral peptide drug delivery. VI. Carbomer and chitosan improve the intestinal absorption of the peptide drug buserelin in vivo, Pharm. Res., 13 1668-1672 (1996). 

Buserelin (Suprefact) and leuprolide (Lupron) are peptide analogues of the hypothalamic hormone LH-RH (luteinizing hormone-releasing hormone). Chronic exposure of the pituitary to these agents abolishes gonadotropin release and results in markedly decreased estrogen and testosterone production by the gonads. Their major clinical use is in the palliative hormonal therapy of cancer of the prostate. 

Gonadotropin-releasing hormone (GnRH) analogs buserelin acetate goserelin acetate leuprolide acetate nafarelin acetate... 

GnRH and its analogs (nafarelin, buserelin, etc) have become important in both stimulating and inhibiting ovarian function. They are discussed in Chapter 37. 

In 67 premenopausal Japanese women randomized to 4-weekly, low-dose buserelin 1.8 mg or leuprorelin 1.88 mg, women given leuprorelin had a more rapid clinical response and a higher rate of hot flushes (2). 

A 49-year-old woman developed Graves disease after receiving buserelin acetate for 4 months. 

A woman with type 2 diabetes had worse glycemic control while receiving buserelin (34). Her blood glucose returned to its previous concentration after withdrawal. 

A 48-year-old woman developed an itchy skin eruption and spotted dark brown pigmentation 3 weeks after starting nasal buserelin 900 micrograms/day. The lesions resolved when buserelin was withdrawn, and recurred with rechallenge some persisted for up to 2 years (43). 

Kono T, Ishii M, Taniguchi S. Intranasal buserelin acetate-induced pigmented roseola-like eruption. Br J Dermatol 2000 143(3) 658-9. 

Local injection reactions are common and probably dose-related. In an open study of cetrorelix in its lowest effective dose of 0.25 mg/day, 3 of 346 women described local reactions (7). In another study of 154 women, 115 of whom were randomized to one 3 mg dose of cetrorelix, 25% had transitory redness or itching at the injection site (2). In a multicenter European study of 463 women randomized to ganirelix and 238 to buserelin, 17% of those given ganirelix had moderate skin redness, bruising, pain, or itching 1 hour after subcutaneous injection this had mostly disappeared after 4 hours (8). 

The in vivo effect of TMC on intestinal absorption was investigated using the peptide drug buserelin (MW 1240), a metabolically stable LH-RH analogue. A 40% and a 60%... 

Thanou, M., et al. 2000. N-trimethylated chitosan chloride (TMC) improves the intestinal permeation of the peptide drug buserelin in vitro (Caco-2 cells) and in vivo (rats). Pharm Res 17 27. 

Raehs, S.C., et al. 1988. The adjuvant effect of bacitracin on nasal absorption of gonadorelin and buserelin in rats. Pharm Res 5 689. 

---