Soto Gustavo Adolfo Centeno, Ruiz-Antorán Belén, Laporta Rosalía, Sancho Arantxa, Lázaro María Teresa, Herrera Concepción Payares, Salcedo Isabel, Cos Maria Angeles, Torres Ferrán, Usetti Piedad, Avendaño-Sola Cristina
Clinical Pharmacology Department, Puerta de Hierro-Majadahonda University Hospital, Calle Manuel de Falla, 1, 28222, Majadahonda, Spain.
Pneumology Department, Puerta de Hierro-Majadahonda University Hospital, Madrid, Spain.
Eur J Clin Pharmacol. 2015 Jun;71(6):715-722. doi: 10.1007/s00228-015-1859-2. Epub 2015 May 9.
The aim of this pharmacokinetic (PK) study was to evaluate tacrolimus (TAC) exposure in stable cystic fibrosis (CF) lung transplant (LT) recipients, converted from TAC twice daily to TAC once daily in an open-label, prospective, single-centre study.
Eligible patients were post-transplant CF patients (18-65 years) with stable lung function, on stable doses of TAC twice daily and who were candidates to switch to TAC once daily. Twelve consecutive patients were included in the study. Patients had their first PK analysis on day 1, still under the stable TAC twice-daily regimen, and were converted to TAC once daily from day 2 onwards. The doses were adjusted according to clinical judgement to achieve target levels, and a second 24-h PK period profile was obtained once the patient was on a stable dosage on the therapeutic range.
The mean total (SD) daily dose of TAC twice daily at baseline upon enrolment was 0.17 (0.10) mg/kg/day. The mean (SD) daily dose of TAC once daily after adjustments was 0.22 (0.12) mg/kg/day. In order to achieve target C min levels with a similar AUC0-24, 82% of subjects who were converted to TAC once daily required an increase of dose, in a range of 0-66.7%, with a mean dose increase of 28%.
Our study results indicate that the switch for conversion from TAC twice daily to TAC once daily in patients with CF may need dose adjustment in order to reach levels within the therapeutic target.
本药代动力学（PK）研究旨在通过一项开放标签、前瞻性、单中心研究，评估在稳定的囊性纤维化（CF）肺移植（LT）受者中，将他克莫司（TAC）从每日两次给药转换为每日一次给药后的血药浓度。
符合条件的患者为移植后肺功能稳定的CF患者（18 - 65岁），每日两次服用稳定剂量的TAC，且有转换为每日一次服用TAC的指征。连续12例患者纳入研究。患者在第1天进行首次PK分析，此时仍处于稳定的每日两次TAC给药方案下，从第2天起转换为每日一次TAC给药。根据临床判断调整剂量以达到目标水平，当患者在治疗范围内达到稳定剂量后，获取第二个24小时PK周期曲线。
入组时基线期每日两次TAC的平均总（标准差）剂量为0.17（0.10）mg/kg/天。调整后每日一次TAC的平均（标准差）剂量为0.22（0.12）mg/kg/天。为了在相似的AUC0 - 24情况下达到目标Cmin水平，82%转换为每日一次TAC给药的受试者需要增加剂量，增加范围为0 - 66.7%，平均剂量增加28%。
我们的研究结果表明，CF患者从每日两次TAC转换为每日一次TAC给药可能需要调整剂量，以达到治疗目标范围内的血药浓度。
