Retention of paclitaxel in cancer cells for 1 week in vivo and in vitro

Mori, Taisuke; Kinoshita, Yoshiyuki; Watanabe, Ai; Yamaguchi, Takeshi; Hosokawa, Kiyohito; Honjo, Hideo

doi:10.1007/s00280-006-0209-6

Cited by 66 publications

(47 citation statements)

References 22 publications

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“…It depends on a large number of parameters, some of which are changed by the effects of the drug, which makes predictions even more difficult. Irreversible binding to microtubules 17 and the detection of paclitaxel in solid tumors 1 week after a single intravenous administration in patients 35 give some indications of the peculiarity of its pharmacokinetics.…”

Section: Speck Et Al Pharmacokinetics Explain Restenosis Inhibitionmentioning

confidence: 99%

Do Pharmacokinetics Explain Persistent Restenosis Inhibition by a Single Dose of Paclitaxel?

Speck

Cremers²,

Kelsch³

et al. 2012

Circ: Cardiovascular Interventions

135

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Background-The purpose of this study was to investigate the elimination of paclitaxel from the arterial wall after a single short administration with a coated balloon. Methods and Results-Slightly oversized paclitaxel-coated balloons (dose 3 or 9 g/mm 2 ) without or with premounted stents were inflated in nonatherosclerotic coronary arteries of either young domestic pigs or adult Goettingen minipigs. The paclitaxel content of plasma, arterial segments, and residual hearts (without treated arteries) was measured for up to 180 days using high-performance liquid chromatography/ultraviolet detection or mass spectrometry. Angiograms were evaluated for lumen narrowing. The paclitaxel concentration in plasma remained Ͻ10 ng/mL. In arteries of domestic pigs and minipigs treated with paclitaxel-coated balloons with premounted stents, 10%Ϯ5% or 21%Ϯ8% of dose, respectively, was initially detected and decreased to 3.5%Ϯ3.1% of dose (domestic pig) by Day 7. Within 6 months it fell with a half-life of 1.9 months to 0.40%Ϯ0.35%. After 3 months the concentration in the arterial wall was 17Ϯ11 mol/L. Without a stent, drug transfer to the vessel wall was somewhat reduced and elimination faster. Immediately after treatment up to 26%Ϯ4% of dose was detected in the residual whole hearts. It dropped with a half-life of 45 days to 1.5%Ϯ0.6% of dose (0.3 mol/L) within 6 months. Conclusions-After

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Section: Speck Et Al Pharmacokinetics Explain Restenosis Inhibitionmentioning

confidence: 99%

Do Pharmacokinetics Explain Persistent Restenosis Inhibition by a Single Dose of Paclitaxel?

Speck

Cremers²,

Kelsch³

et al. 2012

Circ: Cardiovascular Interventions

135

View full text Add to dashboard Cite

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“…4,[17][18][19] Persistence of paclitaxel in the vessel wall after a single local administration with a coated balloon has been proposed as one mechanism of action for PCB. 20 Irreversible binding to microtubules 21 and the detection of paclitaxel in solid tumors 1 week after a single intravenous administration in patients 22 give some indication of the peculiarity of its pharmacokinetics. Although paclitaxel is the only drug on clinically proven and US Food and Drug Administration approved balloon catheters, coronary interventions are dominated by limuseluting stents.…”

mentioning

confidence: 99%

Novel Sirolimus–Coated Balloon Catheter

Clever

Peters

Calisse

et al. 2016

Circ: Cardiovascular Interventions

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Background-Limus-eluting stents are dominating coronary interventions, although paclitaxel is the only drug on balloon catheters with proven inhibition of restenosis. Neointimal inhibition by limus-coated balloons has been shown in few animal studies, but data from randomized clinical trials are not available. The aim of the present preclinical studies was to achieve high and persistent sirolimus levels in the vessel wall after administration by a coated balloon. Methods and Results-Different coating formulations and doses were studied in the porcine coronary model to investigate sirolimus tissue levels at different time points as well as efficacy at 1 month using quantitative coronary angiography and histomorphometry. Loss of the selected coating in the valve, guiding catheter, and blood was low (2±14% of dose). Acute drug transfer to the vessel wall was 14.4±4.6% with the crystalline coating, whereas the amorphous coatings were less effective in this respect. Persistence of sirolimus in the vessel wall until 1 month was 40% to 50% of the transferred drug. At 1-month follow-up, a modest but significant reduction of neointimal growth was demonstrated in a dose range from 4 μg/mm 2 to 2×7 μg/mm 2 , for example, maximum neointimal thickness of 0.38±0.13 versus 0.65±0.21 mm in the uncoated control group. Conclusions-Various Methods Research StrategyA variety of sirolimus balloon-coating formulations were prepared and tested with the primary aim of achieving high transfer rates to the arterial wall and long-lasting persistence in the vessel wall because of increased crystal formation. Other important properties were minimal loss of the drug on the way to the treatment site, inhibition of injury-induced neointimal proliferation, and good local and systemic tolerance. Materials and Coating of BalloonsConventional percutaneous transluminal coronary angioplasty balloon catheters (SeQuent [Neo], B. Braun Melsungen AG, Berlin, Germany) were coated using different coating formulations, coating procedures, and dosages (Table 1; Figure 1). Sirolimus was produced according to Good Manufacturing Practice by Euticals S.p.A., Site of Rozzano, Italy; solvents were USP or analytic grade. Coating was performed in a dose range of ≤7-μg sirolimus per mm 2 balloon surface by dispersing a precisely defined volume of organic solvents containing sirolimus with different matrix-forming additives on the balloons.The different coating procedures resulted in different physicochemical properties in terms of amorphous and crystalline characteristics.After coating, the catheters were left to dry for at least 24 hours at room temperature before use or further processing. For some of the experiments, bare stainless steel stents (B. Braun AG, Melsungen. Germany) were mounted onto balloons using a hand crimper HH100-101 (Machine Solutions, Flagstaff, AZ). Balloon catheters used for determination of sirolimus loss in blood on the way to the coronary artery were left without stents. Balloon catheters used for the animal studies were EO sterilized b...

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“…Somewhat surprisingly, only a short exposure time with drug coated balloons is required to achieve prolonged inhibition of neointimal proliferation [3][4][5][6]. The efficacy of paclitaxel coated balloon catheters may be at least in part attributable to prolonged retention of paclitaxel in cells [25], the coating method applied [3,4], and the fact that PCB provide, within a very short time, a dose that is several times higher than the dose released by paclitaxel eluting stents over the course of several weeks [5]. Furthermore, paclitaxel is a microtubule-stabilizing antiproliferative drug, irreversibly blocking cell cycle progression in the G 2 /M phase.…”

Section: Discussionmentioning

confidence: 99%