Concentrations of isosorbide dinitrate, isosorbide-2-mononitrate and isosorbide-5-mononitrate in human vascular and muscle tissue under steady-state conditions.
The concentrations of isosorbide dinitrate (ISDN), isosorbide-5-mononitrate (IS-5-MN) and isosorbide-2-mononitrate (IS-2-MN) were determined in plasma (PL), saphenous vein wall (SV) and pectoral muscle (PM) from 8 patients undergoing coronary bypass surgery. The patients were pretreated for 2 days with ISDN 240 mg per day (standard release formulation) in 4 doses of 40 mg and one dose of 80 mg. The plasma and tissue samples were obtained during the operation, 10-12 h after the last dose. Isosorbide-2-mononitrate and isosorbide-5-mononitrate were present in plasma and tissues in the same concentration ranges with molar concentration ratios of 0.88 (IS-2-MN: PM/PL), 0.85 (IS-5-MN: PM/PL), 0.99 (IS-2-MN: SV/PL) and 1.06 (IS-5-MN: SV/PL). Mean ISDN concentrations in tissue were considerably higher than in plasma; the molar concentration ratios were 4.9 (SM/PL) and 7.21 (SV/PL). The accumulation of ISDN in vessel walls may contribute to its greater vascular action compared to the mononitrates, but it may also facilitate the development of tolerance during long-term treatment.
Schneider
W
W
Division of Cardiology, University Hospital Frankfurt a.M., Federal Republic of Germany.
Menke
G
G
Heidemann
R
R
Satter
P
P
Kaltenbach
M
M
Rietbrock
N
N
D000368:Aged; D002849:Chromatography, Gas; D006801:Humans; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism*
C030398:isosorbide-2-mononitrate; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate