Richards Patrick G, Dang Kimberlyn M, Kauffman Carol A, Stalker Kay Lyn, Sudekum David, Kerr Lisa, Brinker-Bodley Michelle, Cheriyan Beena, West Nina, Collins Curtis D, Polega Shikha, Malani Anurag N
Department of Pharmacy, St Joseph Mercy Hospital, Ann Arbor, MI, USA.
Scripps Memorial Hospital, La Jolla, CA, USA.
J Antimicrob Chemother. 2017 Apr 1;72(4):1178-1183. doi: 10.1093/jac/dkw550.
A high-dose 12 mg/kg/day (6 mg/kg twice daily) voriconazole regimen was recommended by the CDC to treat patients injected with contaminated methylprednisolone acetate that caused a multi-state fungal outbreak in 2012-13. Therapeutic drug monitoring results of this unique regimen are unknown, as is the most appropriate dosing weight for obese patients. We evaluated voriconazole trough measurements for this dosing scheme, as well as the use of adjusted body weight dosing for obese patients.
Voriconazole trough levels were analysed in obese (BMI ≥35 kg/m 2 ) and non-obese (BMI <35 kg/m 2 ) patients who were given initial therapy with 12 mg/kg/day.
Of 138 patients, the first steady-state voriconazole troughs were supratherapeutic (>5 mg/L) in 65 (47%) patients, therapeutic (2-5 mg/L) in 57 (41%) patients and subtherapeutic (<2 mg/L) in 16 (12%) patients. Twenty-three patients had pre-steady-state dose decreases due to supratherapeutic levels, with subsequent first steady-state troughs in the therapeutic ( n = 17) and subtherapeutic ( n = 6) categories. Voriconazole doses >11 and >8 mg/kg/day produced mainly first steady-state supratherapeutic troughs in 44 obese and 94 non-obese patients, respectively. An initial 12 mg/kg/day was progressively lowered to a median maintenance dose of 8.5 mg/kg/day in the obese and 8.6 mg/kg/day in the non-obese.
A high-dose voriconazole regimen produced initial supratherapeutic troughs that required dose adjustment downward by nearly 30%. Adjusted body weight dosing in obese patients resulted in a similar maintenance dose to total body weight dosing in the non-obese, and appears to be a sensible dosing strategy for these patients.
美国疾病控制与预防中心（CDC）推荐采用高剂量12毫克/千克/天（每日两次，每次6毫克/千克）的伏立康唑治疗方案，用于治疗2012 - 2013年因注射受污染的醋酸甲泼尼龙而引发多州真菌疫情的患者。这种独特治疗方案的治疗药物监测结果尚不清楚，肥胖患者最合适的给药体重也是未知的。我们评估了该给药方案的伏立康唑谷浓度测量值，以及肥胖患者采用调整体重给药的情况。
对接受12毫克/千克/天初始治疗的肥胖（体重指数[BMI]≥35千克/平方米）和非肥胖（BMI＜35千克/平方米）患者的伏立康唑谷浓度进行分析。
在138例患者中，首次稳态伏立康唑谷浓度在65例（47%）患者中高于治疗浓度（＞5毫克/升），57例（41%）患者处于治疗浓度（2 - 5毫克/升），16例（12%）患者低于治疗浓度（＜2毫克/升）。23例患者因谷浓度高于治疗浓度在达到稳态前降低了剂量，随后首次稳态谷浓度处于治疗浓度（n = 17）和低于治疗浓度（n = 6）类别。伏立康唑剂量＞11毫克/千克/天和＞8毫克/千克/天分别在44例肥胖患者和94例非肥胖患者中主要产生首次稳态高于治疗浓度的谷浓度。肥胖患者初始剂量12毫克/千克/天逐渐降至中位维持剂量8.5毫克/千克/天，非肥胖患者降至8.6毫克/千克/天。
高剂量伏立康唑治疗方案最初产生高于治疗浓度的谷浓度，需要将剂量下调近30%。肥胖患者采用调整体重给药与非肥胖患者采用总体重给药的维持剂量相似，似乎是这些患者合理的给药策略。
