Buserelin bioavailability

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. 

Matsubara, K., et al. 1995. Improvement of nasal bioavailability of luteinizing hormone-releasing hormone agonist, buserelin, by cyclodextrin derivatives in rats. J Pharm Sci 84 1295. 

This luteinizing hormone-releasing hormone has been used in the treatment of endometriosis and hormone-dependent tumors. Modes of administration have included injections, nasal sprays and subcutaneous implantations. One study, conducted in pigs, demonstrated the value of glycodeoxycholate (a penetration enhancer) in improving the bioavailability of buserelin by up to five-fold after buccal delivery. ... 

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]. 

The nasal administration was shown to be an effective administration route for lipophilic active substances like fentanyl. Moreover, the nasal route has also been used for the systemic administration of small peptides like buserelin acetate, nafarelin acetate and desmopressin, aU of them containing ten or less amino acid residues. However, for these molecules the nasal route forms only a poor non-invasive alternative to injection, since the nasal bioavailability of these peptides is less than 3-5 %. 

Commercially available peptide hormones delivered as nasal spray solutions include Synarel (nafare-lin), Stimate NS (desmopressin), Suprefact (buserelin acetate), and Miacalcin (salmon calcitonin). A list of current drugs in the market, doses, and bioavailability along with a comparative bioavailability profile for oral desmopressin is presented in Table 86.3. 

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