Abstract
The influence of sodium taurodihydrofusidate (STDHF) was studied on nasal insulin absorption in rabbits and rats as well as on human nasal ciliary movement in vitro. The fusidate derivative at 1% (w/v) enhanced nasal insulin bioavailability from 0.9 to 5.2% and from 0.3 to 18.0% in rabbits and rats, respectively. In both species the insulin formulations with STDHF resulted in strong hypoglycemic responses. As measured in vitro with human adenoid tissue, STDHF was found to induce irreversible ciliostasis at concentrations of 0.3% and higher. This absorption promoter appeared to be less ciliostatic than deoxycholate or laureth-9, but more ciliotoxic than glyco- and taurocholate. Human insulin has no ciliostatic potency, whereas a combination of insulin (1%) and STDHF (1%) is ciliostatic but not as toxic as STDHF (1%) alone. Thus it can be concluded that STDHF is a potent enhancer of nasal insulin absorption, but that its utility in long-term nasal insulin therapy may be limited due to the observed ciliostatic effects.
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Verhoef, J., Hermens, W.A.J.J., Deurloo, M.J.M., Romeijn, S.G., Schipper, N.G.M., Merkus, F.W.H.M. (1990). Intranasal Delivery of Insulin: Absorption Enhancement by the Fusidate Derivative STDHF in Rabbits and Rats and Effects on Human Nasal Ciliary Movement in Vitro. In: Crommelin, D.J.A., Schellekens, H. (eds) From Clone to Clinic. Developments in Biotherapy, vol 1. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-3780-5_40
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