LHRH analogs

Kent et al. first reported on the feasibility of controlled release LHRH analogs from a 50 50 lactide/glycolide copolymer (118,119)... 

Delivery systems for several steroids, LHRH analogs, and naltrexone have been described. A priori, a constant rate of release from a... 

FIGURE 17 Use of a porous PCL membrane to achieve diffusion-controlled zero-order deliveiry of a LHRH analog from a reservoir device. (From Ref. 72.)... 

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... 

LHRH analogs Goserelin 3.6 mg SC every 28 days Hot flashes, amenorrhea, menopausal symptoms,... 

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. 

A. S. Dutta, B. J. A. Furr (1985). Luteinizing hormone releasing hormone (LHRH) analogs. Annu. Rep. Med. Chem. 20 203-214. 

There are fewer reports on other parenteral routes of administration of emulsions such as intramuscular, subcutaneous, and intraperitoneal. V Mer-in-oil and w/o/w emulsions of bleomycin, mytomycin C, and 5-Luorouracil have been administered by these routes, apparently resulting in increased regional lymphatic uptake, hence the term lymphotropic emulsions (Davis et al., 1987). Gasco et al. (1990) developed a w/o emulsion of an LHRH analog measurements of testosterone levels after intramuscular administration to rats suggested that the formulation led to prolonged release of the drug. 

Roy, S.D. de Groot, J.S. Percutaneous absorption of nafarelin acetate, an LHRH analog, through human cadaver skin and monkey skin. Int. J. Pharm. 1994, 110, 137-145. 

Luteinizing hormone-releasing hormone (LHRH) analogs Abarelix Goserelin Leuprolide Triptorelin pamoate Progestins... 

Flutamide, a nonsteroidal antiandrogen (250 mg p.o. q. 8 hours), is indicated in the treatment of metastatic prostatic carcinoma in combination with LHRH analogs, such as leuprolide acetate (see also Table 13). 

P2 gel-former, is the most effective in reducing POA, and to a lesser extent, the LHRH analog, triptoreline acetate, the NSAID naproxen and, possibly trapidil, are effective in the same vehicle. 

Contributions from industrial laboratories are not less significant. For instance the work of Masumi Itoh on the prevention of racemization in coupling originates from the research laboratory of the Fugisawa company in Osaka. Masahiko Fujino of Takeda Chemical Industries, established the fundamental principles for the design of superactive LHRH analogs. 

Early work in this area was published in several articles by Sanders and co-workers, who described the use ofpoly(D,L-lactide-co-glycolide) (PLGA) microcapsules for the delivery of the peptide nafarelin acetate, an LHRH analog [(D-Nal(2) Aza-Gly >)-LHRH Syntex] (Anik et al, 1984 Sanders et al, 1984, 1985, 1986). Microcapsules were produced by a coacervation microencapsulation technique, and the release of the peptide was shown to be predominately triphasic (Fig. 1)—high initial release lasting for several hours, followed by a period of low or limited release, and finally several days... 

Okada and co-workers (1988,1989,1991) and Ogawa etal. (1988) have also described a 75 25 PLGA microencapsulated 30-day release system for the delivery of another LHRH analog leuproUde acetate [(D-Leu , Pro NEt)-LHRH Lupron Depot , Takeda-Abbott], Their results indicate that a single injection of microcapsules maintains constant and effective serum levels of the analog for one month. Sufficient therapeutic efficacy in the treatment of advanced prostatic cancer has also been shown for leuprolide acetate, and the product has recently been approved for use by the U.S. Food and Drug Administration (Lupron Depot , 7.5mg PDR, 1994). This treatment has also shown to cause a dramatic regression of... 

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