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J Pharm Sci. 2018 Feb;107(2):764-769. doi: 10.1016/j.xphs.2017.10.008. Epub 2017 Oct 13.

Suitability of the AUC Ratio as an Indicator of the Pharmacokinetic Advantage in HIPEC.

Author information

1
Division of Pharmacy and Pharmaceutics, Department of Engineering, School of Pharmacy, Miguel Hernández University, San Juan de Alicante, Alicante, Spain.
2
Division of Pharmacy and Pharmaceutics, Department of Engineering, School of Pharmacy, Miguel Hernández University, San Juan de Alicante, Alicante, Spain; Alicante Institute for Health and Biomedical Research (ISABIAL-FISABIO Foundation), Alicante, Spain.
3
Department of Pathology and Surgery, School of Medicine, Miguel Hernández University, San Juan de Alicante, Alicante, Spain.
4
Division of Pharmacy and Pharmaceutics, Department of Engineering, School of Pharmacy, Miguel Hernández University, San Juan de Alicante, Alicante, Spain; Alicante Institute for Health and Biomedical Research (ISABIAL-FISABIO Foundation), Alicante, Spain; Clinical Pharmacokinetics Unit, Pharmacy Department, Alicante University General Hospital, Alicante, Spain.
5
Division of Pharmacy and Pharmaceutics, Department of Engineering, School of Pharmacy, Miguel Hernández University, San Juan de Alicante, Alicante, Spain; Alicante Institute for Health and Biomedical Research (ISABIAL-FISABIO Foundation), Alicante, Spain. Electronic address: jnalda@umh.es.

Abstract

The purpose of this study was to evaluate the area under the concentration-time curve (AUC) ratio as an optimal indicator of the pharmacokinetic advantage during hyperthermic intraperitoneal perioperative chemotherapy. The impact on the AUC ratio on the variables related to the calculation of systemic drug exposure, instillation time, and peripheral drug distribution was evaluated through simulations as well as through a retrospective analysis of studies published in the literature. Both model simulations and the retrospective analysis showed that the 3 variables evaluated had an impact on the AUC ratio value if the complete systemic exposure was not fully considered. However, when that complete systemic exposure was considered, none of these variables affected the AUC ratio value. AUC ratio is not a characteristic parameter of a drug if the calculated systemic drug exposure is not complete. Thus, AUC ratio is not valid for comparing the pharmacokinetic advantage of 2 drugs, and it should not be employed to prove whether a drug can be used in hyperthermic intraperitoneal perioperative chemotherapy safely with regard to toxicity. As an alternative, the study of the absorption rate constant and the bioavailability are proposed as the true and independent parameters that reflect the amount of drug absorbed.

KEYWORDS:

Absorption; Cancer chemotherapy; Clearance; Clinical pharmacokinetics; Mathematical models; Simulations

PMID:
29031954
DOI:
10.1016/j.xphs.2017.10.008
[Indexed for MEDLINE]

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