Pharmacodynamic model of dopamine D1 receptor agonists in the treatment of breast cancer lung metastasis

doi:10.5246/jcps.2020.01.004

Abstract

Abstract:

Previous study has shown that dopamine D1 receptor (D1DR) agonists, fenoldopam (FEN) and l-stepholidine (l-SPD), have inhibitory effects on breast cancer lung metastasis. To quantitatively describe and predict the pharmacodynamic (PD) properties of FEN and l-SPD and to explore the PD model structure of cancer metastasis treating drugs, we used the data of lung metastasis in 4T1 breast cancer mice under the treatment of either FEN or l-SPD, and established a PD model. The PD model assumed an exponential growth for both primary tumor and metastasis. The primary tumor emitted cells to form metastases, and the cell emitting rate was proportional to power form of the primary tumor weight. The total number of lung metastasis was set as the target value. D1DR agonists inhibited metastasis by inhibiting cell emitting rate instead of the growth rate of primary tumor or metastasis. The model results showed that the decrease in the number of lung metastases was roughly proportional to the square of the drug dose. The values of PD coefficient reflected the inhibitory ability of the drugs, and that of l-SPD (0.274 kg/mg) was greater than that of FEN (0.0393 kg/mg). This PD model can quantitatively describe the effects of FEN and l-SPD on the progression of lung metastasis in 4T1 primary breast cancer mice and can predict the time course of drug efficacy at multiple doses, providing a reference for PD model structure of other drugs for cancer metastasis indication.

Key words: Pharmacodynamic model, Dopamine D1 receptor agonist, Cancer metastasis, Breast cancer

CLC Number:

R962

Supporting:

Liang Yang, Ye Yao, Yaoyao Feng, Wei Lu, Tianyan Zhou. Pharmacodynamic model of dopamine D1 receptor agonists in the treatment of breast cancer lung metastasis[J]. Journal of Chinese Pharmaceutical Sciences, 2020, 29(1): 45-54.

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