Frequency and Severity of Neutropenia Associated with Food and Drug Administration Approved and Compounded Formulations of Lomustine in Dogs with Cancer.
Frequency and Severity of Neutropenia Associated with Food and Drug Administration Approved and Compounded Formulations of Lomustine in Dogs with Cancer.
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与食品和药物管理局相关的中性粒细胞减少症的频率和严重程度在患有癌症的狗中批准和复合的配方。
DOI：
10.1111/jvim.13805
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发表时间：
2016-01
影响因子：
2.6
通讯作者：
Rebhun RB
中科院分区：
文献类型：
--
作者：
Burton JH;Stanley SD;Knych HK;Rodriguez CO;Skorupski KA;Rebhun RB
复合洛莫司汀通常用于兽医患者。然而，这些配方中的潜在变异性是未知的，人们担心药物的复合配方可能与食品和药物管理局(FDA)批准的产品在效力上不同。这项研究的最初目标是评估使用复合或FDA批准的洛莫司汀制剂治疗的狗的中性粒细胞减少的频率和严重程度。随后的分析旨在确定从几家复方药店获得的洛莫司汀的效力。37只狗接受了FDA批准的或复合洛莫司汀的治疗。接受复合或FDA批准的洛莫司汀，并进行了预处理和低谷CBCs的狗符合纳入条件。评估的变量包括洛莫司汀剂量、中性粒细胞计数和中性粒细胞减少的严重程度。采用高效液相色谱-紫外检测法对5种来源的洛莫司汀5 mg胶囊进行了效价测定。21只狗接受了FDA批准的洛莫斯汀，16只狗接受了由单一复方药房开出的洛莫斯汀治疗。所有接受FDA批准的洛莫司汀治疗的狗在治疗后都出现了中性粒细胞减少；15只狗(71%)出现了3级或更高的中性粒细胞减少。4只狗(25%)服用复合洛莫司汀后中性粒细胞减少，其中2只狗(12.5%)发展为3级中性粒细胞减少。5家复方药店的洛莫司汀效价为标示浓度的50%~115%，1个样品的标示浓度在±10%以内。这些数据支持对复合化疗药物的效力和一致性进行更广泛的调查，并突出了对这些产品进行更多监督的潜在必要性。
Compounded lomustine is used commonly in veterinary patients. However, the potential variability in these formulations is unknown and concern exists that compounded formulations of drugs may differ in potency from Food and Drug Administration (FDA)‐approved products. The initial objective of this study was to evaluate the frequency and severity of neutropenia in dogs treated with compounded or FDA‐approved formulations of lomustine. Subsequent analyses aimed to determine the potency of lomustine obtained from several compounding pharmacies. Thirty‐seven dogs treated with FDA‐approved or compounded lomustine. Dogs that received compounded or FDA‐approved lomustine and had pretreatment and nadir CBCs performed were eligible for inclusion. Variables assessed included lomustine dose, neutrophil counts, and severity of neutropenia. Lomustine 5 mg capsules from 5 compounding sources were tested for potency using high‐pressure liquid chromatography (HPLC) with ultraviolet (UV) detection. Twenty‐one dogs received FDA‐approved lomustine and 16 dogs were treated with lomustine prescribed from a single compounding pharmacy. All dogs treated with FDA‐approved lomustine were neutropenic after treatment; 15 dogs (71%) developed grade 3 or higher neutropenia. Four dogs (25%) given compounded lomustine became neutropenic, with 2 dogs (12.5%) developing grade 3 neutropenia. The potency of lomustine from 5 compounding pharmacies ranged from 50 to 115% of the labeled concentration, with 1 sample within ±10% of the labeled concentration. These data support broader investigation into the potency and consistency of compounded chemotherapy drugs and highlight the potential need for greater oversight of these products.