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Cancer Chemother Pharmacol. 2013 Nov;72(5):1111-23. doi: 10.1007/s00280-013-2288-5. Epub 2013 Sep 24.

Circadian variability of pharmacokinetics of cisplatin in patients with non-small-cell lung carcinoma: analysis with the NONMEM program.

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1
Department of Pharmacy and Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiang Su, China.

Abstract

PURPOSE:

The aim of this study was to describe the nonlinear pharmacokinetics of total and unbound plasma cisplatin under different administered time in patients with non-small-cell lung carcinoma.

METHODS:

Patients receiving chemotherapy with cisplatin were included in this analysis. Patients were divided into two groups depending on the administrated time of cisplatin: 6:00 (Group A) and 18:00 (Group B). The population pharmacokinetics of cisplatin was calculated using nonlinear mixed-effects modeling (NONMEM) method, and the possible influence of covariates on the population pharmacokinetics of cisplatin was also explored.

RESULTS:

The pharmacokinetics of total and unbound cisplatin could be described well by a linear two-compartment model. The mean population estimates for total and unbound drug were, respectively, 0.463 (17.0 %) and 25.4 (14.0 %) l h⁻¹ for clearance (CL), 24.2 (19.9 %) and 20.5 (27.1 %) l for central distribution volume (V₁), 10.2 (18.2 %) and 9.82 (28.1) l h⁻¹ for intercompartmental clearance (Q) and 32.0 (24.1 %) and 6.77 (25.4 %) l for peripheral compartment volume (V₂). The CL for total and unbound cisplatin was dependent on body surface area (BSA). When cisplatin was administered at 18:00, the CL was 1.38- and 1.22-fold higher than those administered at 6:00 for total and unbound cisplatin, respectively (P < 0.05). The mean parameter estimates from a nonparametric bootstrap procedure were comparable and within 5 % of the estimates from NONMEM.

CONCLUSIONS:

The results showed that circadian could influence the metabolism of cisplatin and suggested the conventional dose adjustment of cisplatin based on BSA.

PMID:
24061864
DOI:
10.1007/s00280-013-2288-5
[Indexed for MEDLINE]
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