Department of Clinical Pharmacy, School of Pharmacy, University of Colorado Cancer Center, Mail Stop C238, 12850 East Montview Blvd., V20-1223, Aurora, CO, 80045, USA.
Cancer Chemother Pharmacol. 2012 Mar;69(3):605-12. doi: 10.1007/s00280-011-1733-6. Epub 2011 Sep 22.
To compare the pharmacokinetic (PK) parameters of a single dose of erlotinib in cancer patients with moderate hepatic impairment (MHI) to those of cancer patients with adequate hepatic function (AHF).
Cancer patients with either AHF or MHI were treated with a single 150 mg dose of erlotinib on day 1 only followed by 96 h of plasma sampling for PK assessment. From day 5, patients were allowed to continue daily erlotinib in a maintenance phase. Non-smoking patients were stratified into an AHF cohort (total bilirubin ≤ upper limit of normal [ULN] and ALT/AST ≤ 1.5 X ULN) or a MHI cohort (Child-Pugh score of 7-9). The frequency of adverse events and laboratory changes were assessed.
Thirty-six patients, 21 with AHF and 15 with MHI, received at least one dose of erlotinib. The PK of erlotinib was similar between the two cohorts with a median C (max) of 1.09 versus 0.828 μg/mL and corresponding median AUC(0-t ) 29.3 versus 30.5 μg h/mL for the AHF and MHI cohorts, respectively. Adverse events from erlotinib in cancer patients with MHI were consistent with the known safety profile.
The PK and safety profiles of erlotinib in patients with MHI were similar to those with AHF. As a result, a reduced starting dose of erlotinib in patients with MHI is not required and treatment should be guided by patients' tolerability.
比较中重度肝损害（MHI）和肝功能正常（AHF）的癌症患者单次厄洛替尼的药代动力学（PK）参数。
仅在第 1 天，MHI 和 AHF 癌症患者接受 150mg 厄洛替尼单剂量治疗，随后进行 96 小时的 PK 评估。从第 5 天开始，患者在维持阶段可以继续每日服用厄洛替尼。非吸烟患者分为 AHF 队列（总胆红素≤正常值上限[ULN]和 ALT/AST≤1.5×ULN）或 MHI 队列（Child-Pugh 评分 7-9）。评估不良事件和实验室变化的频率。
36 例患者（21 例 AHF 和 15 例 MHI）至少接受了一剂厄洛替尼。两个队列的厄洛替尼 PK 相似，AHF 队列的中位 C（max）为 1.09μg/mL，相应的中位 AUC（0-t）为 29.3μg·h/mL，MHI 队列的中位 C（max）为 0.828μg/mL，相应的中位 AUC（0-t）为 30.5μg·h/mL。MHI 癌症患者使用厄洛替尼的不良反应与已知的安全性特征一致。
MHI 患者的厄洛替尼 PK 和安全性特征与 AHF 患者相似。因此，MHI 患者无需降低厄洛替尼的起始剂量，应根据患者的耐受性来指导治疗。
