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. 2021 Apr;87(4):501-511.
doi: 10.1007/s00280-020-04220-y. Epub 2021 Jan 8.

Population pharmacokinetic model development and exposure-response analysis of vincristine in patients with malignant lymphoma

Toshiaki Igarashi  1 , Shinji Kishi  2   3 , Naoko Hosono  3 , Takashi Higashi  4 , Takahiro Iwao  5 , Ryoichi Yano  4   6 , Hitoshi Tsukamoto  4 , Nobuyuki Goto  4 , Takahiro Yamauchi  3 , Takanori Ueda  3
Affiliations

Population pharmacokinetic model development and exposure-response analysis of vincristine in patients with malignant lymphoma

Toshiaki Igarashi et al. Cancer Chemother Pharmacol. 2021 Apr.

Abstract

Purpose: Vincristine (VCR) is a key drug for treating various malignancies. However, few data are available on the pharmacokinetics of VCR, especially in adult patients. The objective of this study was to clarify the population pharmacokinetics and exposure-response relationships of VCR in adult malignant lymphoma patients.

Methods: Blood samples were collected from patients who were administered R-CHOP-like regimens, and the VCR plasma concentration was determined using liquid chromatography-mass spectrometry. Using NONMEM software, population pharmacokinetic parameters were estimated, and covariates were evaluated. The relationships between the individual parameters and adverse events or therapeutic effects were also investigated.

Results: Plasma concentrations were measured in 30 patients. In the final population pharmacokinetics model, body surface area and age were incorporated into clearance as significant covariates. The inter-individual variations in clearance and volume of distribution in the central and third compartments were 17.0, 26.6, and 66.3%, respectively, and the residual variability in the plasma concentration was 23.8%. Although the variability observed in the volume of distribution was large, good predictability was obtained in the individual estimation. The severity of anemia and peripheral neuropathy was correlated with clearance and peak concentration, respectively (adjusted P = 0.040 and 0.024, respectively). In diffuse large B cell lymphoma patients, those with higher area under the curve and dose experienced longer progression-free survival (P = 0.023 and 0.013, respectively).

Conclusion: The population pharmacokinetics of VCR were evaluated in adult malignant lymphoma patients. VCR pharmacokinetic data could explain in part the adverse events and prognosis of these patients.

Keywords: Malignant lymphoma; Pharmacodynamics; Population pharmacokinetics; Vincristine.

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References

    1. Jordan MA, Wilson L (2004) Microtubules as a target for anticancer drugs. Nat Rev Cancer 4(4):253–265. https://doi.org/10.1038/nrc1317 - DOI - PubMed
    1. van de Velde ME, Kaspers GL, Abbink FCH, Wilhelm AJ, Ket JCF, van den Berg MH (2017) Vincristine-induced peripheral neuropathy in children with cancer: a systematic review. Crit Rev Oncol Hematol 114:114–130. https://doi.org/10.1016/j.critrevonc.2017.04.004 - DOI - PubMed
    1. Sethi VS, Jackson DV Jr, White DR, Richards F 2nd, Stuart JJ, Muss HB, Cooper MR, Spurr CL (1981) Pharmacokinetics of vincristine sulfate in adult cancer patients. Can Res 41(9 Pt 1):3551–3555
    1. Vendrig DE, Teeuwsen J, Holthuis JJ (1988) Analysis of vinca alkaloids in plasma and urine using high-performance liquid chromatography with electrochemical detection. J Chromatogr 424(1):83–94. https://doi.org/10.1016/s0378-4347(00)81078-6 - DOI - PubMed
    1. Ramírez J, Ogan K, Ratain MJ (1997) Determination of vinca alkaloids in human plasma by liquid chromatography/atmospheric pressure chemical ionization mass spectrometry. Cancer Chemother Pharmacol 39(4):286–290. https://doi.org/10.1007/s002800050574 - DOI - PubMed

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