Jeong In Hwan, Ryu Sooyoon, Han Nayoung, Staatz Christine E, Baek In-Hwan
College of Pharmacy, Kyungsung University, 309, Suyeong-ro, Nam-gu, Busan, 48434, Republic of Korea.
College of Pharmacy, Jeju National University, 102 Jejudaehak-ro, Jeju, 63241, Republic of Korea.
Clin Pharmacokinet. 2025 Feb;64(2):285-295. doi: 10.1007/s40262-024-01471-3. Epub 2025 Jan 14.
Telmisartan exhibits significant pharmacokinetic (PK) variability, but it remains unclear whether its PK profile is altered in hypertensive patients. This study aimed to characterize telmisartan PKs by conducting a meta-analysis and developing a pooled population PK model based on data from healthy subjects and hypertensive patients.
Relevant literature was identified by a systematic approach. Eighteen studies were selected for analysis, which included 394 healthy subjects receiving single doses of telmisartan, 190 healthy subjects receiving repeated doses, along with 295 hypertensive patients receiving repeated doses. Pooled population PK analysis incorporated 20 mean concentration-time profiles from 14 studies. Meta-analyses were performed using OpenMeta-Analyst, and population PK modeling was performed using NONMEM.
Repeated telmisartan doses increased peak plasma concentrations. However, other noncompartmental PK parameters remained consistent across healthy and hypertensive populations. Telmisartan PKs were best described using a two-compartment model with first-order absorption and elimination in pooled analysis. Typical PK parameter values for apparent clearance (CL/F), apparent central and peripheral volumes of distribution (V/F and V/F), absorption rate constant (k), and absorption lag time were 18.3 L/h, 20.7 L, 360 L, 0.183 h and 0.228 h, respectively. Interindividual variabilities in CL/F, V/F, and k were 84%, 122%, and 106%, respectively. Covariate analysis revealed significantly lower CL/F (63.7%) and V/F (90.3%) values in hypertensive patients than healthy subjects.
These findings quantified the variability of telmisartan PK profile and highlighted the differences between healthy individuals and hypertensive patients, suggesting the need for optimized dosage strategies to improve therapeutic outcomes.
替米沙坦存在显著的药代动力学（PK）变异性，但尚不清楚其PK特征在高血压患者中是否改变。本研究旨在通过进行荟萃分析并基于健康受试者和高血压患者的数据建立汇总的群体PK模型，来表征替米沙坦的PK特性。
通过系统方法识别相关文献。选择18项研究进行分析，其中包括394名接受单剂量替米沙坦的健康受试者、190名接受重复剂量的健康受试者以及295名接受重复剂量的高血压患者。汇总群体PK分析纳入了来自14项研究的20条平均浓度-时间曲线。使用OpenMeta-Analyst进行荟萃分析，使用NONMEM进行群体PK建模。
替米沙坦重复给药会增加血浆峰浓度。然而，其他非房室PK参数在健康人群和高血压人群中保持一致。在汇总分析中，替米沙坦的PK特性最好用具有一级吸收和消除的二室模型来描述。表观清除率（CL/F）、表观中央和外周分布容积（V/F和V/F）、吸收速率常数（k）和吸收滞后时间的典型PK参数值分别为18.3 L/h、20.7 L、360 L、0.183 h和0.228 h。CL/F、V/F和k的个体间变异性分别为84%、122%和106%。协变量分析显示，高血压患者的CL/F（63.7%）和V/F（90.3%）值显著低于健康受试者。
这些发现量化了替米沙坦PK特征的变异性，并突出了健康个体与高血压患者之间的差异，表明需要优化给药策略以改善治疗效果。
