Comparison of steady state pharmacokinetics of isosorbide-5-mononitrate in microgranular formulation or hydrophilic matrix
Centonze, F.; Brambilla, M.; Pittana, P.; Serra, G.; Sega, R.
La Clinica Terapeutica 126(3): 195-206
1988
ISSN/ISBN: 0009-9074 PMID: 2974386 Document Number: 316772
The pharmacokinetics of isosorbide-5-mononitrate (IS-5-MN) were studied in six male volunteers after treatment with single daily doses of either a microgranular formulation (M; 50 mg) or a formulation in hydrophilic matrix (I; 40 mg) for five consecutive days. Analysis of pharmacokinetics showed M to be more readily absorbed than I (latent period 3.0 vs 42.6 min., p < 0.01) and thus to achieve higher short-term plasma levels (at 1 hour: 287.6 vs 192.7 ng/ml; p < 0.05) and to be present in the organism for longer times (9.0 vs 8.2 hrs; p < 0.05). Steady state pharmacokinetics attending once daily dosage of M appeared to have clinico-therapeutic advantages compared to the findings observed with administration of I, both because effective plasma levels were more readily achieved without a latent period and because the absorption curve was more regular and thus guaranteed a more favorable therapeutic coverage; in addition peaks were less high both after a single dose and in steady state conditions which therefore carried a lower risk of untoward reactions; the circadian variations of circulating levels were smaller with consequently a lower risk of tolerance.