Bioaequivalence of sublingual glycerol trinitrate. Bioavailability and haemodynamic effects after application of a fluorochlorohydrocarbons-dependent spray and a new pumping system.

Bioaequivalence of glycerol trinitrate (GTN, CAS 55630) was investigated in 16 healthy volunteers after sublingual application of 2 x 0.41 mg GTN from two different spray-formulations (A: fluorochlorohydrocarbons (FHC)-dependent formulation; B: FHC-free pumping system). Plasma concentrations of GTN (measured by a gas chromatographic method) and haemodynamic effects (measured by digital plethysmography) were monitored 30 min after application. EC50 of the individual concentration-effect curves were calculated and linked to the individual concentration-time curves to establish the time of reaching EC50 (tEC50). AUC0-infinity, Cmax, tmax and the haemodynamic parameters were compared intraindividually (Wilcoxons matched pairs sign rank test), bioequivalence of B to A was tested on the basis of nonparametric 95%-confidence intervals (Tukey). There was no significant difference in the AUC0-infinity (A: 14.2 ng min/ml, B: 16.3 ng min/ml), but significant differences were obtained in Cmax (A: 1.41 ng/ml, B: 2.77 ng/ml, p less than 0.01) and tmax (A: 6.8 min, B: 3.9 min, p less than 0.01). The confidence intervals of the ratio B/A were 0.81-1.56 for AUC0-infinity, 1.3-3.13 for Cmax and 0.50-0.58 for tmax. The GTN-response did not differ after both formulations (EC50 A: 0.441 ng/ml, EC50 B: 0.421 ng/ml), but significant differences were observed for tEC50 (A: 2.82 min, B: 1.05 min, p less than 0.01). Preparation B exhibits a superior bioavailability and a more rapid onset of haemodynamic efficacy.