Pharmacokinetic profiles of cancer sonochemotherapy

ABSTRACT

Introduction: Sonochemotherapy is a promising strategy for the treatment of cancer, however, there is limited understanding of its pharmacokinetics (PK).

Area covered: The PK profile of sonochemotherapy is evaluated based on released data. Preclinical investigations suggest that the blood PK of sonochemotherapy is similar to chemotherapy when using free anticancer drugs. When using encapsulated drugs, a lower plasma level usually occurs; however, the ultrasonic release of drugs within a tumor may lead to drugs leaking into circulation, causing a rebound in the plasma drug level; a higher drug level is detected in certain healthy organs, however this depends mostly on the pharmaceutical formulation. Sonochemotherapy increases both the level and retention time of drugs in a tumor. Clinical trials of combined chemotherapy and high intensity focused ultrasound (HIFU) are evaluated from the perspective of preclinical PK: the intratumoral PK and drug interactions under insonation, and a protocol to set the interval between drug administration and insonation are lacking.

Expert opinion: Insonation can alter the PK properties of chemotherapeutics, which may exacerbate the system and/or organ toxicity of anticancer drugs. Directly employing the PK parameters validated in conventional chemotherapy plays an important role in unsatisfactory clinical outcomes of chemotherapy combined with HIFU.

KEYWORDS:

• Sonochemotherapy
• pharmaceutical form
• blood pharmacokinetics
• tissue distribution
• intratumoral pharmacokinetics
• high intensity focused ultrasound

Article highlights

• The blood PK is usually not changed when using free anticancer drugs.

• The ultrasonic release of drugs in a tumor may lead to a leak of drugs from the tumor into circulation when using encapsulated drugs, causing a rebound in the plasma drug level.

• Tissue distribution may be altered when using encapsulated drugs, resulting in a higher drug level in certain healthy organs.

• The clinical efficacy of the combination of chemotherapy and HIFU is unsatisfactory: directly adopting the PK parameters validated in chemotherapy plays a crucial role.

• Effects of insonation on the PK property (particularly for a combined regimen) should be explored in translational researches.

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Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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Funding

This work was supported with grants from the National Natural Science Foundation of China (31470822) and the State Ministry of Education (SRFDP 20135503130002).