Buserelin absorption

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). 

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%... 

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

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. 

Raehs SC, Sandow J, Wirth K, Merkle HP (1988) The adjuvant effect of bacitracin on nasal absorption of gonadorelin and buserelin in rats. Pharm Res 5 689-693 Ramon J, Saez V, Baez R, Aldana R, Hardy E (2005) PEGylated Interferon-alpha2b A Branched 40K Polyethylene Glycol Derivative. Pharm Res 22 1375-1387 Reseland JE, Holm H, Jacobsen MB, Jenssen TG, Hanssen LE (1996) Proteinase inhibitors induce selective stimulation of human trypsin and chymotrypsin secretion. J Nutr 126 634-642... 

Chitosan and its derivatives have been applied to enhance the absorption of proteins (e.g., insulin) and polypeptides (e.g., buserelin). /V-Trimethyl chitosan chloride exhibits opening of the tight junctions of the intranasal and intestinal epithelial cells so that the transport of hydrophilic compounds is increased through the para-cellular transport pathway. The absorption-enhancing effect was concentration dependent and reversible and dependent on the integrity of the intercellular cell contact zone. 

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. 

A range of nasal peptides such as desmopressin, buserelin, nafarelin and oxytocin, have been formulated into licensed nasal products. However, none of them contains a nasal absorption enhancer. Even though these nasal products are characterised by low peptide bioavailability they are efficacious, as low systemic levels are needed to exert a therapeutic effect. However, developing of novel safe and efficient nasal absorption enhancers is of great interest to improve bioavailability of presently marketed peptides and to provide sufficient nasal permeability of less potent biologicals [22]. 

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. 

Gel formulation Buserelin Enhancement of intestinal absorption of the peptide drug [83]... 

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