Peptide buserelin

In medicines with intended systemic action a certain pH may be necessary to guarantee sufficient absorption of the active substance. In that case a buffer with high capacity is chosen, although it will have a negative effect on cilia. The more pH deviates from the physiological value, the more irritation will be felt. An example is a licensed nasal spray with the peptide buserelin in a citrate buffer (pH 5.5-6). Its Summary of product characteristics (SPC) says nasal irritation may occur, sometimes leading to epistaxis or hoarseness, as well as changes in taste and smell. 

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. 

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. 

Hoogstraate, A., et al. 1996. In vivo buccal delivery of the peptide drug buserelin with glycodeoxycholate as an absorption enhancer in pigs. Pharm Res 13 1233. 

Drugs that are routinely administered intranasally include peptides such as vasopressin and its analog desmopressin, luteinizing hormone-releasing hormone, buserelin, leuprolide, nafarelin,... 

Hoogstraate, A.J. Coos Verhoef, J. Pijpers, A. van Leengoed, L.A. Verheijden, J.H. Junginger, H.E. Bodde, H.E. In vivo buccal delivery of the peptide drug buserelin with glycodeoxycholate as an absorption enhancer in pigs. Pharm. Res. 1996,13, 1233-1237. 

Successful nasal delivery of peptide compounds has led to a number of peptide drugs being marketed for systematic absorption. These peptide drugs include buserelin (Supre-fact , Hoechst), gonadorelin (Kryptocur , Hoechst), protirelin (Relefact TRH nasal, Hoechst), calcitonin (Miacalcic , Sandoz), nafarelin (Synarel , Syntex) and desmopressin (Minirin , Ferring). Table 13.5 summarises the characteristics of some peptides studied in the nose. 

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