Octreotide bioavailability

Oechslein, Fricker, and Kissel " studied various powder formulations of mucoadhesive polymers for their efficacy to increase the nasal absorption of octreotide in rats. Although chitosan showed the highest water uptake (chitosan > microcrystalline cellulose > semicrystalline cellulose > pectin = hydroxyethyl starch = alginic acid = Sephadex G25), the highest peptide drug bioavailability was found after coadministration of alginic acid and Sephadex G25 powders (4.1 and 5.56%, respectively). The authors concluded that the calcium-binding properties of the polymers used correlated better with the increased octreotide 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. 

Octreotide was also administered to juvenile pigs with or without TMC60 at a pH of 7.4. The solutions were administered intrajejunally through an in-dwelling fistula that was inserted 1 week prior to the octreotide. Intrajejunal administration of 10 mg of octreotide, co-administered with 5 and 10% (w/v) TMC60, resulted in a 7.7-fold and 14.5-fold increase in octreotide absorption with absolute bioavailabilities of 13.9 1.3 and 24.8 1.8%, respectively. The results are presented in Fig. 6.5 (Thanou et al. 2001a). 

A slightly different approach is to deliver the active drug in a dry powder carrier system, for example microcrystalline cellulose, hydroxyethyl starch, cross-linked dextran, microcrystalline chitosan, carbomer, pectin, or alginic acid. The polymer absorbs water upon contact with the nasal mucosa and swells to become a viscous gel, often demonstrating bioadhesive properties. Such systems can remain in the nasal cavity for as long as six hours. For example, the bioavailability in rats of the somatostatin analogue, octreotide, was shown to be enhanced by the co-administration of alginic acid and cross-linked dextran as dry powders. 

C. As a polypeptide, it is bioavailable only by parenteral administration (intravenously or subcutaneously). Approximately 30% of octreotide is excreted unchanged in the urine, and it has an elimination half-life of 1.7 hours. Its half-life may be increased in patients with renal dysfunction and in the elderly. 

Octreotide modestly increases the bioavailability of bromocriptine, whereas bromocriptine does not appear to alter octreotide pharmacokinetics. 

The combined use of bromocriptine 5 mg twice daily and subcutaneous octreotide 200 mierograms twiee daily increased the bioavailability of bromocriptine by about 40%, without altering its elearance or half-life. The pharmaeokinetics of octreotide were unchanged. This effect may contribute to the increased effieaey of eombined treatment in acromegaly shown in some studies. Bear it in mind when considering eombined ther-apy. 

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