Sublingual application

17a-methyltestosterone was found to be more effective when applied sublingually than when ingested orally (Escamilla 1949). This type of substitution should, however, not be practised because of the liver toxicity of methyltestosterone summarized above. The solubility of the hydrophobic testosterone molecule can be enhanced by incorporation into hydroxypropyl-S-cyclodextrins (Pitha et al. 1986) which are macro-ring structures consisting of cyclic oligosaccharides. When testosterone incorporated into such cyclodextrins is administered sublingually steep increases in serum testosterone occur lasting for one or two hours (Stuenkel et al. 1991). Hypogonadal men treated with three daily doses for 60 days showed improvement of their condition (Salehian et al. 1995; Wang et al. 1996). This is an interesting approach to testosterone substitution, but unless more constant serum levels can

Time (hours)

Fig. 14.3 Mean (±SD), baseline-adjusted serum concentrations of testosterone after application of placebo (solid line), 10 mg (squares), 20 mg (triangles) and 30 mg (diamonds) of buccal testosterone at steady state (day 10 of dosing). Broken lines indicate normal range of testosterone (adapted from Baisley et al. 2002, reproduced by permission of the Society of Endocrinology).

Time (hours)

Fig. 14.3 Mean (±SD), baseline-adjusted serum concentrations of testosterone after application of placebo (solid line), 10 mg (squares), 20 mg (triangles) and 30 mg (diamonds) of buccal testosterone at steady state (day 10 of dosing). Broken lines indicate normal range of testosterone (adapted from Baisley et al. 2002, reproduced by permission of the Society of Endocrinology).

be achieved this therapy would require repeated daily applications and would have the same disadvantages as conventional oral testosterone undecanoate therapy.

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