CLINICAL PHARMACOLOGICAL EQUIVALENCE OF A NOVEL FCH FREE GTN SPRAY WITH LOW ETHANOL CONTENT VS A FCH CONTAINING GTN SPRAY

The overall therapeutic equivalence of a fluorochlorohydrocarbon (FCH) -free glyceryl trinitrate (GTN) pump spray with a low ethanol content (TL) was investigated relative to an FCH-containing GTN spray (Nitroli ngual; R), in terms of: (1) pharmacokinetic bioavailability, (2) pharm acodynamic responses as assessed by digital plethysmography (DPG), and (3) clinical perception upon application. Pharmacokinetically, the ti me courses of the plasma concentrations of GTN and its dinitrate metab olites, 1.2- and 1.3-GDN, subsequent to the sublingual administration of 0.8 mg GTN showed somewhat lower bioavailability of GTN and its met abolites than to the reference. Pharmacodynamically, the changes in th e DPG signals after the application of 0.8 mg GTN with TL were biostat istically euivalent with R (estimated ratio TL/R for the maximum decre ase of the ratio between the systolic a wave and c incisure: 0.98; 90 % CI: 0.84-1.14; and for the average decrease of the c: a ratio: 0.97; 90 % CI: 0.80-1.16). The time of occurrence of the maximum effect of TL was not significantly different from that of R (estimated differenc e TL-R: -2.25 min; 95 % CI: -9.5 min to 2 min). In contrast. after the administration of an FCH-free GTN spray with a higher ethanol content (TH, active control), the effect had a slightly earlier onset (TH R: -6 min, 95 % CI: -9.5 to -2 min) and there was a higher average respon se (TH/R: 1.12: 90 % CI: 0.95 to 1.34). However, TH was consistently j udged to cause an extremely unpleasant burning sensation in the mouth and thus was perceived as distinctly different from R. In contrast, TL was well tolerated and could not be distinguished from R. Therefore o nly TL met the criteria of overall therapeutic equivalence to R.