Pharmacokinetic study of a new synthetic MMP inhibitor (Ro 28-2653) after IV and oral administration of cyclodextrin solutions

Piette, M; Évrard, Brigitte; Frankenne, Françis; Chiap, Patrice; Bertholet, Pascal; Castagne, Delphine; Foidart, Jean‐Michel; Delattre, Luc; Piel, Géraldine

doi:10.1016/j.ejps.2006.01.011

Cited by 16 publications

(7 citation statements)

References 28 publications

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“…Aqueous solubility of the Ro 28-2653 inclusion complex with hydroxypropyl--cyclodextrin and l-lysine was 7000 times higher than the uncomplexed drug [35]. The results of in vivo evaluation showed that absorption of the Ro 28-2653 inclusion complex in sheep was faster than the uncomplexed control.…”

Section: Application In Analysis Of Mmp Inhibitors and Their Metabolimentioning

confidence: 83%

Matrix Metalloproteinase Inhibitors: A Review on Bioanalytical Methods, Pharmacokinetics and Metabolism

Wang

Li²,

Adams³

et al. 2011

CDM

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Enzymes are major drug targets in drug discovery and development processes in the pharmaceutical and biotechnology industry. A recent survey found that nearly half of all the marketed small-molecule drugs are inhibitors of enzymes. Matrix metalloproteinases (MMPs) are a family of 28 enzymes capable of degrading the constituents of the extracellular matrix (ECM) and the basement-membrane. MMPs play an essential role in several normal physiological processes including growth, wound healing and tissue repair. Over-expression and activation of MMPs has been linked to a range of diseases which include osteoarthritis, tumor metastasis, angiogenesis and cardiovascular diseases. The development of MMP inhibitors as therapeutic agents has kept an important place in drug discovery. Therefore, there is also an increasing need for robust analytical methods for evaluation of inhibitory potency and for the analysis of MMP inhibitors and their metabolites which can even play a more significant role than the parent drug. Modern analytical techniques and hyphenated instrumentations such as liquid chromatography-mass spectrometry with a function of structure elucidation can provide a profound insight into the research of MMP inhibitors and also serve as a complementary method to zymographic techniques for the analysis of biological samples. This review mainly summarizes bioanalytical methods, pharmacokinetics and related metabolites of MMP inhibitors over the last 12 years.

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Section: Application In Analysis Of Mmp Inhibitors and Their Metabolimentioning

confidence: 83%

Matrix Metalloproteinase Inhibitors: A Review on Bioanalytical Methods, Pharmacokinetics and Metabolism

Wang

Li²,

Adams³

et al. 2011

CDM

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“…This release behavior might be due to the inclusion compound entering the blood and under certain conditions; the guest molecules would be released from the hydrophobic cavity of the host molecule to the human body to produce pharmacological effects. Due to the stronger affinity with the hydrophobic cavity of HP‐β‐CD, a large number of endogenous lipids competed with drugs to replace butylphthalide [43]. In this release process, HP‐β‐CD and butylphthalide return to a free state from the polymer, so we saw in the concentration–time curve that the inclusion compound was “absorbed” in the body after intravenous injection into the blood, which is essentially the release of the free body into the blood.…”

Section: Resultsmentioning

confidence: 99%

Development of an LC‐MS/MS method for simultaneous quantitative analysis of macromolecular pharmaceutical adjuvant 2‐hydroxypropyl‐β‐cyclodextrin and active pharmaceutical ingredients butylphthalide in rat plasma

Cang

Sun

et al. 2021

J of Separation Science

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Hydroxypropyl-β-cyclodextrin, which possesses a high water solubility and low hemolycity, is widely used as a solubilizer and an excipient. It had also been reported that hydroxypropyl-β-cyclodextrin has the activity of regulating lipid homeostasis. In order to further understand the metabolism, the primary focus was to establish a quantitative method for hydroxypropyl-βcyclodextrin. The analytes were extracted from plasma by protein precipitation with methanol and then carried out on a Waters CORTECS T3 column in the gradient elution of pure water and methanol. Finally, liquid chromatographytandem mass spectrometry was applied in multiple reaction monitoring mode to complete the quantitative analysis of hydroxypropyl-β-cyclodextrin. This validated method had been successfully applied to investigate the interaction between hydroxypropyl-β-cyclodextrin and butylphthalide in vivo by optimizing the extraction reagent, simplifying the experimental procedure, and improving the sensitivity while considering the difference of drug chemical properties. Results showed that the inclusion of hydroxypropyl-β-cyclodextrin with butylphthalide significantly improved the pharmacokinetic behavior of free body hydroxypropyl-β-cyclodextrin and 3-n-butylphthalide in vivo. It had been implied that the metabolism of hydroxypropyl-β-cyclodextrin and the drug active ingredients could impact each other. It will help better application of hydroxypropyl-β-cyclodextrin and the developed method might lay the foundation for development of hydroxypropyl-β-cyclodextrin as a treatment drug for brain diseases.

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“…Both formulations were administered orally to sheep at a dose of 15 mg/kg. The absolute bioavailability was significantly higher with the solution (80%) than with the suspension (8%) [50]. Similarly, Yavuz and collaborators prepared inclusion complexes between exemestane (EXE) and MCD, HPCD or HPCD [47].…”

Section: Tablementioning

confidence: 99%

Molecular Buckets: Cyclodextrins for Oral Cancer Therapy

Calleja

Huarte

Agüeros

et al. 2011

Therapeutic Delivery

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The oral route is preferred by patients for drug administration due to its convenience, resulting in improved compliance. Unfortunately, for a number of drugs (e.g., anticancer drugs), this route of administration remains a challenge. Oral chemotherapy may be an attractive option and especially appropriate for chronic treatment of cancer. However, this route of administration is particularly complicated for the administration of anticancer drugs ascribed to Class IV of the Biopharmaceutical Classification System. This group of compounds is characterized by low aqueous solubility and low intestinal permeability. This review focuses on the use of cyclodextrins alone or in combination with bioadhesive nanoparticles for oral delivery of drugs. The state-of-the-art technology and challenges in this area is also discussed.

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Pharmacokinetic study of a new synthetic MMP inhibitor (Ro 28-2653) after IV and oral administration of cyclodextrin solutions

Cited by 16 publications

References 28 publications

Matrix Metalloproteinase Inhibitors: A Review on Bioanalytical Methods, Pharmacokinetics and Metabolism

Matrix Metalloproteinase Inhibitors: A Review on Bioanalytical Methods, Pharmacokinetics and Metabolism

Development of an LC‐MS/MS method for simultaneous quantitative analysis of macromolecular pharmaceutical adjuvant 2‐hydroxypropyl‐β‐cyclodextrin and active pharmaceutical ingredients butylphthalide in rat plasma

Molecular Buckets: Cyclodextrins for Oral Cancer Therapy

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