BACKGROUNDLipophilic taxanes can be dissolved in contrast media at significantly higher concentration than in saline. As contrast media have occasionally been observed to delineate the contour of coronary arteries for some seconds they may serve as a matrix for an antiproliferative drug aimed at preventing restenosis. The aim of this study was to test a novel taxane-contrast agent formulation for this new approach in the setting of coronary stenting.METHODS AND RESULTSIn cell culture experiments (bovine vascular smooth muscle cells), 60-min incubation with contrast agent-taxane formulations (iopromide-paclitaxel, iopromide-protaxel) induced a significant, concentration-dependent inhibition of vascular smooth muscle cell (VSMC) proliferation over 12 days. Shorter incubation times of 10 and 3 min showed the same efficacy. For in vivo investigation, 16 stents were implanted into the coronary arteries of eight pigs using a 1.3 to 1 overstretch ratio. A control group received iopromide 370 alone while the treatment group was injected with a iopromide-protaxel formulation at a dose of 74 micromol/l, which is far below protaxel levels inducing systemic toxicity. Quantitative angiography and histomorphometry of the stented arteries asserted statistic equality of the baseline parameters between the control and treatment groups. After 28 days, the treatment group showed a marked reduction of the parameters characterizing in-stent restenosis, especially a 34% reduction of the neointimal area.CONCLUSIONSFirst evidence is provided that using a contrast agent as solvent for a taxane constitutes a new drug delivery mechanism able to inhibit in-stent restenosis in the porcine restenosis model.

2002-01-01·Investigative Radiology1区 · 医学

Acute Cardiac Tolerance of Current Contrast Media and the New Taxane Protaxel Using Iopromide as Carrier During Porcine Coronary Angiography and Stenting

1区 · 医学

Article

作者: Clauss, Wolfram ; Scheller, Bruno ; Stoll, Hans-Peter ; Sovak, Milos ; Schmitt, Alexander ; Speck, Ulrich ; Bohm, Michael

RATIONALE AND OBJECTIVESThe systemic tolerance thresholds of modern low-osmolar x-ray contrast media (CM) are similarly high, but their effects on the cardiovascular system and on the coagulation differ. The aim of this study was to comparatively evaluate the cardiovascular tolerability of iopromide, ioxaglate, and iosmin, and of a novel taxane protaxel, dissolved in iopromide, as a carrier, by coronary angiography and stenting.METHODSSixteen pigs were randomized into four groups: iosmin (350 mg iodine/mL, n = 4, nonionic dimer), iopromide (370 mg iodine/mL, n = 4, nonionic monomer), ioxaglate (320 mg iodine/mL, n = 4, ionic dimer), and 70-micromol protaxel dissolved in iopromide 370 mg iodine/mL, intended to prevent restenosis. Coronary angiography was performed via the left carotid artery followed by implantation of stents into the left anterior descending and the circumflex arteries. About 80 mL per animal was used in each group.RESULTSThere were no thrombotic complications and no significant adverse events of electrocardiography, blood pressure, or contractility during or after CM injections. There were no differences among the CM tested except that ioxaglate was the only agent showing a significant reduction in dp/dt after 50 seconds compared to iosmin. The values of preinjection parameters were most rapidly regained after iosmin, compared with other CM tested.CONCLUSIONSThe novel iso-osmolar nonionic CM iosmin is well tolerated in porcine coronary angiography and subsequent stenting. The cardiac tolerance of iopromide has not been adversely affected by addition of the cytostatic protaxel.

2001-04-01·Anti-Cancer Drugs4区 · 医学

A new prodrug of paclitaxel: synthesis of Protaxel

4区 · 医学

Article

作者: Seligson, Allen L. ; Douglass, James G. III ; Bressi, Jerome C. ; Terry, Ronald C. ; Sovak, Milos

2' and 7 Polyol carbonates of paclitaxel were synthesized and screened as potential paclitaxel prodrugs. Paclitaxel is released from 7-(2",3"-dihydroxypropylcarbonato) paclitaxel (Protaxel) at rates inversely proportional to pH, by an intramolecular cyclization. Compared to paclitaxel, maximum tolerated i.v. or i.p. doses (MTD) of Protaxel are about 2.5- to 3-fold higher; its efficacy is substantially higher in human cancer line xenografts in athymic mice, especially in prostate PC-3, breast MDA-MB 468 and ovary OVCAR-1.

100 项与 Paclitaxel ceribate 相关的药物交易

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