The pharmacokinetics of tacrolimus in peripheral blood mononuclear cells and limited sampling strategy for estimation of exposure in renal transplant recipients.
Purpose: Intracellular exposure of tacrolimus (TAC) may be a better marker of therapeutic effect than whole blood exposure. We aimed to evaluate the influence of genetic polymorphism on the pharmacokinetics of TAC in peripheral blood mononuclear cells (PBMCs) and develop limited sampling strategy (L...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 78; no. 8; pp. 1261 - 1273 |
|---|---|
| Autores principales: | , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Springer Nature
Aug2022
|
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=157988211&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 157988211 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Aug2022 vid: 78 iid: 8 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 157988211 156782693 157988211 157988211 10.1007/s00228-021-03215-9 157988211 ppf: 1261 ppct: 12 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: The pharmacokinetics of tacrolimus in peripheral blood mononuclear cells and limited sampling strategy for estimation of exposure in renal transplant recipients. aug: au: Wang, Xi-Han Shao, Kun An, Hui-Min Zhai, Xiao-Hui Zhou, Pei-Jun Chen, Bing affil: Department of Pharmacy, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China sug: subj: Tacrolimus Pharmacokinetics Blood Cells Drug Effects Polymorphism, Genetic Physiology Kidney Transplantation Transplant Recipients Human Immunosuppression Descriptive Statistics ab: Purpose: Intracellular exposure of tacrolimus (TAC) may be a better marker of therapeutic effect than whole blood exposure. We aimed to evaluate the influence of genetic polymorphism on the pharmacokinetics of TAC in peripheral blood mononuclear cells (PBMCs) and develop limited sampling strategy (LSS) models to estimate the area under the curve (AUC0–12h) in the PBMC of Chinese renal transplant patients. Methods: Ten blood samples of each of the 23 renal transplant patients were collected 0–12h after 14 (10–18) days of TAC administration. PBMCs were separated and quantified. The TAC level in PBMCs was determined, and pharmacokinetic parameters were estimated by noncompartmental study. The AUC0–12h of TAC in whole blood was estimated by Bayesian approach based on a population pharmacokinetic model established in 65 renal transplant patients. The influence of CYP3A5 and ABCB1 genotypes on exposure was estimated. By applying multiple stepwise linear regression analysis, LSS equations for TAC AUC0–12h in the PMBC of renal transplant patients were established, and the bias and precision of various equations were identified and compared. Results: We found a modest correlation between TAC exposure in whole blood and PBMC (r2 = 0.5260). Patients with the CYP3A5 6986GG genotype had a higher AUC0–12h in PBMCs than those with the 6986 AA or GA genotype (P = 0.026). Conversely, patients with the ABCB1 3435TT genotype had a higher AUC0–12h in PBMC than those with the 3435 CC and CT genotypes (P = 0.046). LSS models with 1–4 blood time points were established (r2 = 0.570–0.989). The best model for predicting TAC AUC0–12h was C2–C4–C6–C10 (r2 = 0.989). The model with C0.5–C6 (r2 = 0.849) can be used for outpatients who need monitoring to be performed in a short period. Conclusions: The CYP3A5 and ABCB1 genotypes impact TAC exposure in PBMCs, which may further alter the effects of TAC. The LSS model consisting of 2–4 time points is an effective approach for estimating full TAC AUC0–12h in Chinese renal transplant patients. This approach may provide convenience and the possibility for clinical monitoring of TAC intracellular exposure. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|