Miceli Marisa H, Perissinotti Anthony J, Kauffman Carol A, Couriel Daniel R
Division of Infectious Diseases, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI.
Department of Pharmacy, University of Michigan Health System, Ann Arbor, MI.
Mycoses. 2015 Jul;58(7):432-6. doi: 10.1111/myc.12339. Epub 2015 Jun 23.
The posaconazole extended release tablet formulation was developed to improve bioavailability relative to the oral suspension. Therapeutic drug monitoring has been used to optimise posaconazole dosing to achieve a target trough level ≥0.7 μg ml(-1). We retrospectively evaluated 28 patients with haematological malignancies who received posaconazole tablets for antifungal prophylaxis. Posaconazole serum trough levels were obtained 5 days after initiation of therapy. Mean trough level was 1.19 ± 0.63 μg ml(-1), and 71% achieved a trough level ≥0.7 μg ml(-1). Diarrhoea was associated with lower mean trough levels (0.65 ± 0.08 μg ml(-1) vs. 1.31 ± 0.13 μg ml(-1)), P = 0.002. Mean trough levels were lower in patients ≥90 kg (0.74 ± 0.09 μg ml(-1)) vs. <90 kg (1.32 ± 0.14 μg ml(-1)), P = 0.002 and in patients with body mass index (BMI) ≥30 (0.89 ± 0.13 μg ml(-1)) vs. BMI <30 (1.29 ± 0.14 μg ml(-1)), P = 0.05. Posaconazole delayed release tablets attain appropriate trough levels in most patients, but patients with a higher weight and those experiencing diarrhoea are more likely to have lower levels.
泊沙康唑缓释片制剂的研发旨在提高相对于口服混悬液的生物利用度。治疗药物监测已用于优化泊沙康唑剂量，以达到目标谷浓度≥0.7μg/ml。我们回顾性评估了28例接受泊沙康唑片进行抗真菌预防的血液系统恶性肿瘤患者。在治疗开始5天后获得泊沙康唑血清谷浓度。平均谷浓度为1.19±0.63μg/ml，71%的患者谷浓度≥0.7μg/ml。腹泻与较低的平均谷浓度相关（0.65±0.08μg/ml对1.31±0.13μg/ml），P=0.002。体重≥90kg的患者平均谷浓度较低（0.74±0.09μg/ml），而体重<90kg的患者为（1.32±0.14μg/ml），P=0.002；体重指数（BMI）≥30的患者平均谷浓度较低（0.89±0.13μg/ml），而BMI<30的患者为（1.29±0.14μg/ml），P=0.05。泊沙康唑缓释片在大多数患者中能达到适当的谷浓度，但体重较高的患者和出现腹泻的患者更有可能谷浓度较低。
