Pharmacokinetics and tissue distribution of larotaxel in rats: comparison of larotaxel-loaded microsphere with larotaxel-solution

Liu, Zhenzhen; Feng, Yanhui; Zhang, Lunhui; Li, Guofei; Geng, Longlong; Cui, Yan; Teng, Fei; Tang, Xing; Bi, Kaishun; Chen, Xiaohui

doi:10.1007/s00280-013-2104-2

Cited by 14 publications

(10 citation statements)

References 28 publications

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“…In addition, a dose correlation study suggested that the AUC was dose proportional within the experimental doses, although there is a trend towards reduced clearance as the dose increases. Also, there was no significant difference in half‐time (p > 0.05) at three dose levels, further indicating the linear pharmacokinetics of TM‐2 within the experimental doses, which is consistent with other taxanes …”

Section: Resultssupporting

confidence: 77%

“…A rapid initial‐phase half‐life was averaging 4 min followed by an intermediate‐phase half‐life of around 1 h, and then a prolonged terminal‐phase half‐life averaging 6 h was observed. Compared with larotaxel administrated to rats (4 mg/kg), TM‐2 has a lower C max and AUC, a higher plasma clearance, a larger apparent volume of distribution and a longer elimination half‐life . But TM‐2 exhibits similar AUC, C max and plasma clearance to docetaxel (5 mg/kg), although a larger apparent volume of distribution and a longer elimination half‐life was observed .…”

Section: Resultsmentioning

confidence: 92%

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Application of an LC‐MS/MS method to the pharmacokinetics of TM‐2, a potential antitumour agent, in rats

Men

Zhao

Lin

et al. 2014

Drug Testing and Analysis

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TM-2 is a novel semi-synthetic taxane derivative, selected for preclinical development based on its greater anticancer activity and lower toxicity compared with docetaxel. In this study, a rapid and sensitive analytical method based on ultra performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the determination of TM-2 in rat plasma. The biological samples were extracted with methyl tert-butyl ether and separated on a C18 column (50 mm × 2.1 mm, 1.7 µm) using a mobile phase consisting of acetonitrile and 2 mM ammonium acetate. The standard curves were linear over the range 5-1000 ng/mL in rat plasma. The precision (relative standard deviation, RSD, %) were within 14.5%, and the accuracy (relative error, RE, %) ranged from -1.56 to 2.36%. Recovery and matrix effect were satisfactory in rat plasma. The validated method was successfully applied to pharmacokinetic studies after intravenous administration of TM-2 to rats. The pharmacokinetics of TM-2 in rats were characterized by a large volume of distribution and a long half-life of elimination after single dose (4, 8, and 16 mg/kg), and a good correlation was observed between AUC and dose. The preclinical data will be useful for the design of subsequent trials of TM-2.

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Section: Resultssupporting

confidence: 77%

Section: Resultsmentioning

confidence: 92%

Application of an LC‐MS/MS method to the pharmacokinetics of TM‐2, a potential antitumour agent, in rats

Men

Zhao

Lin

et al. 2014

Drug Testing and Analysis

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“…Comparing the tissue distribution of lipid microspheres with that of a solution might explain this. As reported , in contrast to the concentration in the plasma, the larotaxel concentration of lipid microspheres in most tissues was lower that that of a solution formed by adding polysorbate 80. It is believed that CTX could penetrate into tissues faster in solution rather than in lipid microspheres, which resulted in an increased AUC for CTX‐LM.…”

Section: Resultsmentioning

confidence: 54%

Evaluation of the stability and pharmacokinetics of cabazitaxel‐loaded intravenous lipid microspheres: Beneficial effect of cholesterol

Shao

Tian

et al. 2014

Euro J Lipid Sci & Tech

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In this work, we describe the evaluation of the stability and pharmacokinetics of cabazitaxel‐loaded lipid microspheres (CTX‐LM) prepared by high‐pressure homogenization. Investigation of the physicochemical stability under different homogenization cycles and diverse sterilization times confirmed that 8 cycles at 800 bar and 121°C for 8 min were the optimal technological parameters. The beneficial effect of cholesterol on the physical stability of CTX‐LM was confirmed and its mechanism of action was identified. The stability of CTX‐LM using an aqueous isotonic glucose solution as a diluting agent was greater compared with using 0.9% NaCl solution as a result of an electric charge effect. CTX‐LM are stable under freeze‐thaw conditions and should not be exposed to high temperatures and protected from light during storage. Furthermore, all the changes in parameters were within an acceptable range at 4°C within 9 months, which supported the good long‐term stability of CTX‐LM. Finally, to compare the pharmacokinetics of CTX‐LM with cabazitaxel‐solution in vivo, a rapid, accurate UPLC‐MS/MS method was developed and used to determine cabazitaxel in rat plasma after a single intravenous administration of 4 mg/kg. An obviously larger area under the curve (AUC) of CTX‐LM was observed than that of CTX‐solution, which will improve the antitumor efficacy of cabazitaxel. Practical applications: As a novel semisynthetic taxane, cabazitaxel has shown antitumour activity in a broad range of cell‐lines and tumor models and has been approved in combination with prednisone for the treatment of patients with castration‐resistant metastatic prostate cancer. However, serious undesirable effects in humans, such as anaphylactoid hypersensitivity reactions and peripheral neuropathy were produced by the addition of polysorbate 80 to commercial products. In this paper, CTX‐LM was prepared by high‐pressure homogenization in order to overcome the above drawbacks. The good stability and markedly higher AUC of CTX‐LM may hasten their passage from a pre‐clinical phase to a clinical trial phase and allow their production on a large scale. In this paper, cabazitaxel lipid microspheres exhibited a great stability and had a higher AUC than cabazitaxel solution.

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“…A total of 12 rats were randomly divided into two groups, with six in each (Li et al, 2011;Liu et al, 2013). The animal number was calculated based on the power analysis with a power of larger than 80% in the pre-experiment.…”

Section: Pharmacokinetic Study Of Ltx Solution and Modified Liposomesmentioning

confidence: 99%

“…The animal number was calculated based on the power analysis with a power of larger than 80% in the pre-experiment. Group 1 was randomly selected and treated with LTX solution at a dose of 4 mg kg À1 (1 ml of the injection at the concentration 1.0 mg ml À1 of LTX was administered via the tail vein), while a corresponding dose of LTX-loaded liposomes were administered to Group 2 (Kurata et al, 2000;Liu et al, 2013;Robert et al, 2010;Sessa et al, 2002;Yamamoto et al, 2009). Blood samples of about 0.3 ml were collected from the suborbital vein into heparinised centrifuge tubes, at 0.083, 0.167, 0.333, 0.5, 1, 2, 3, 4, 6, 8 and 12 h after dosing.…”

Section: Pharmacokinetic Study Of Ltx Solution and Modified Liposomesmentioning

confidence: 99%

Pharmacokinetics and tissue distribution of larotaxel in rats: comparison of larotaxel solution with larotaxel-loaded folate receptor-targeting amphiphilic copolymer-modified liposomes

Zhou

Zhang

et al. 2016

Xenobiotica

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1. The aim of this study was to compare the pharmacokinetics (PKs) and tissue distribution of larotaxel (LTX) solution with a newly developed formulation called LTX-loaded folate-poly (PEG-cyanoacrylate-co-cholesteryl cyanoacrylate) (FA-PEG-PCHL)-modified liposomes in rats. 2. An ultra-performance liquid chromatography-tandem mass spectrometry method has been developed and validated for the determination of LTX in rat plasma and tissues to investigate the inﬂuence of FA-PEG-PCHL-modified lipid carrier on LTX PKs and tissue distribution. 3. The PK study result showed significantly higher area under the concentration-time curve (97.2%, **p < 0.01), slower clearance (49.2%, **p < 0.01) and lower volume of distribution (42.5%, **p < 0.01) in rats following intravenous administration of modified liposomes. The biodistribution results exhibited significantly lower uptake of LTX-loaded modified liposomes in heart (20.4%, **p < 0.01), lung (8.33%, **p < 0.01), muscle (13.4%, *p < 0.05) and spleen (15.0%, **p < 0.01) among all sampled tissues, indicating that the modified lipid carriers may avoid the trapping by the reticuloendothelial system and the modified liposomes may reduce toxicity in cardiovascular system compared to LTX solution. Moreover, markedly higher concentrations of LTX in the kidney (100%, **p < 0.01) were found in LTX-loaded modified liposome treated rats and could be explained by the high folate receptor level in kidney. 4. These results indicated that the FA-PEG-PCHL-modified liposome could be an effective parenteral carrier for the delivery of LTX in cancer treatment.

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Pharmacokinetics and tissue distribution of larotaxel in rats: comparison of larotaxel-loaded microsphere with larotaxel-solution

Abstract: These results suggest that lipid microsphere could be an effective parenteral carrier for LTX delivery in cancer treatment.

Cited by 14 publications

References 28 publications

Application of an LC‐MS/MS method to the pharmacokinetics of TM‐2, a potential antitumour agent, in rats

Application of an LC‐MS/MS method to the pharmacokinetics of TM‐2, a potential antitumour agent, in rats

Evaluation of the stability and pharmacokinetics of cabazitaxel‐loaded intravenous lipid microspheres: Beneficial effect of cholesterol

Pharmacokinetics and tissue distribution of larotaxel in rats: comparison of larotaxel solution with larotaxel-loaded folate receptor-targeting amphiphilic copolymer-modified liposomes

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