PMID- 38297024 OWN - NLM STAT- MEDLINE DCOM- 20240202 LR - 20240203 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 14 IP - 1 DP - 2024 Jan 31 TI - Population pharmacokinetics of lenalidomide in Chinese patients with influence of genetic polymorphisms of ABCB1. PG - 2577 LID - 10.1038/s41598-024-52460-2 [doi] LID - 2577 AB - Affected by differences in the pharmacokinetics (PK) of lenalidomide, the toxicity of lenalidomide varies among different patients, with serious toxicity leading to dose reduction or discontinuation. The differences in the PK of lenalidomide may be related to factors such as patients' physiological characteristics, pathological characteristics and gene polymorphisms etc., which may also affect its toxicity. The aim of this study is to establish a population pharmacokinetic (PPK) model of lenalidomide and explore factors associated with the adverse events (AEs) of lenalidomide from a PK perspective. Blood samples were collected by opportunistic blood collection. Drug concentrations were determined by using HPLC/MS and genotype of ABCB1 3435 C > T (rs1045642), ABCB1 1236 A > G (rs1128503) and ABCB1 2677 A > C/T (rs2032582) was tested by the first-generation DNA sequencing technology. NONMEM software and SPSS 26.0 software were used respectively to establish PPK model of lenalidomide and explore the correlation between PK parameters and the incidence of serious AEs of lenalidomide. 51 patients were enrolled in the PPK study, and one-compartment model with first-order absorption and elimination agreed well with the observed data. The significant covariate affecting lenalidomide apparent volume of distribution (V/F) were the gene polymorphism of ABCB1 3435 C > T and diet. Safety studies could be conducted in 39 patients. The V/F value in patients suffering from serious AEs was significantly higher than that in others ( median = 67.04 L vs 37.17 L, P = 0.033). According to the covariates screened, the incidence of serious AEs was higher in patients with genotype CT or TT at ABCB1 3435 C > T locus than that in patients with genotype CC (P = 0.039). Additionally, V/F value was the highest in patients carrying genotype TT with postprandial medication, in whom the incidence of serious AEs was higher than others (P = 0.037). In conclusion, the genotype of ABCB1 3435 C > T locus and diet had pharmacokinetically relevant impact on lenalidomide, which may also be related to the incidence of serious AEs. Patients with gene variants of CT or TT at ABCB1 3435 C > T locus may be more susceptible to serious AEs, and monitoring of adverse reactions should be particularly strengthened in patients who carried genotype TT with postprandial medication. CI - (c) 2024. The Author(s). FAU - Liang, Xiaoxiao AU - Liang X AD - Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Clinical Pharmacy, Jinan, Shandong, China. AD - School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China. FAU - Shi, Haiyan AU - Shi H AD - Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Clinical Pharmacy, Jinan, Shandong, China. FAU - Bi, Kehong AU - Bi K AD - Department of Hematology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, China. FAU - Feng, Saran AU - Feng S AD - Department of Hematology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, China. FAU - Chen, Shixian AU - Chen S AD - School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China. FAU - Zhao, Wei AU - Zhao W AD - Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Clinical Pharmacy, Jinan, Shandong, China. FAU - Huang, Xin AU - Huang X AD - Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Clinical Pharmacy, Jinan, Shandong, China. 13791120711@126.com. AD - School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China. 13791120711@126.com. LA - eng GR - 2020YFC2008303，2020YFC2008306/The National Key R&D Program of China/ PT - Journal Article DEP - 20240131 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (ABCB1 protein, human) RN - 0 (ATP Binding Cassette Transporter, Subfamily B) RN - F0P408N6V4 (Lenalidomide) SB - IM MH - Humans MH - *ATP Binding Cassette Transporter, Subfamily B/genetics MH - China MH - Genotype MH - *Lenalidomide/adverse effects/pharmacokinetics MH - Polymorphism, Single Nucleotide MH - *East Asian People/genetics PMC - PMC10830448 COIS- The authors declare no competing interests. EDAT- 2024/02/01 00:42 MHDA- 2024/02/02 06:42 PMCR- 2024/01/31 CRDT- 2024/01/31 23:29 PHST- 2023/10/08 00:00 [received] PHST- 2024/01/18 00:00 [accepted] PHST- 2024/02/02 06:42 [medline] PHST- 2024/02/01 00:42 [pubmed] PHST- 2024/01/31 23:29 [entrez] PHST- 2024/01/31 00:00 [pmc-release] AID - 10.1038/s41598-024-52460-2 [pii] AID - 52460 [pii] AID - 10.1038/s41598-024-52460-2 [doi] PST - epublish SO - Sci Rep. 2024 Jan 31;14(1):2577. doi: 10.1038/s41598-024-52460-2.