BIOAVAILABILITY AND PHARMACOKINETICS OF A NEW ISOSORBIDE DINITRATE SPRAY PREPARATION IN HEALTHY-VOLUNTEERS

In the course of this study the bioavailability and pharmacokinetic pr ofile of a newly developed 2.5 mg (per valve release) oral isosorbide dinitrate (ISDN, CAS 87-33-2) spray preparation (Isoket(R) Spray) were determined and compared with the results for an already marketed refe rence spray preparation following single application. For this purpose , the test and reference spray were examined in 18 healthy volunteers according to a randomized 2-way cross-over design. Blood samples were collected during 12 h pa. and plasma concentrations of ISDN and its me tabolites isosorbide-2-mononitrate (IS-2-MN) and isosorbide-5-mononitr ate (IS-5-MN) were quantified by a GC-method. Both sprays showed mean maximum concentrations Of ISDN in plasma of nearly 18 ng/ml about 7 mi n after drug intake with arithmetic mean values for the areas under th e curve AUC0-12 of 7.01 (test spray) and 7.30 h . ng/ml (reference spr ay). For the metabolic products IS-2-MN and IS-5-MN (values for the re ference spray in brackets) the corresponding maximum concentrations we re 4.15 (4.21) ng/ml and 16.1 (15.9) ng/ml, respectively, and for the areas under the curve AUC0-12 values of 9.75 (9.92) h . ng/ml for IS-2 -MN and 104.3 (99.7) h / ng/ml for IS-5-MN in the mean were calculated . Statistical evaluation of all pharmacokinetic parameters revealed bi oequivalence between the two preparations. Typical side-effects known and described under isosorbide dinitrate therapy were also observed in this study.