Research on pharmacokinetics of high-dose tamoxifen in non-small cell lung cancer patients

Objective: To study the pharmacokinetics of tamoxifen at a high dosage, which will offer a theoretical support for an appropriate clinical use of the medicine in non-small cell lung cancer (NSCLC) patients. Methods: Three qualified NSCLC patients are selected and given tamoxifen (TAM) 160 mg per Os. Blood samples were collected at different times and then analyzed by high-performance liguid chromatography. The PK-GRAPH program was used to obtain the parameters. Results: The concentration-time courses of the TAM 160 mg were fitted to one-compartment model. The pharmacokinetic parameters were estimated as follows: Tmax (6.35 ± 1.24) h, Cmax (217.39 ± 7.71) ng/mL, AUC (12 127.39 ± 636.16) ng·h/mL and T 1/2ke (34.13 ± 2.97) h. Conclusion TAM 160mg one day per Os cannot reach the effective maintenance concentration in vivo required for reversing MDR in vitro. Loading-maintenance dose strategy is recommended to study the pharmacodynamics of tamoxifen at a high dosage in NSCLC patients.