Figus Michele, Posarelli Chiara, Romano Dario, Nardi Marco, Rossetti Luca
Department of Surgical, Medical, Molecular Pathology and of Critical Area, University of Pisa, Via Paradisa, 2, 56100, Pisa, Italy.
Eye Clinic, ASST Santi Paolo e Carlo, University of Milan, Milan, Italy.
Eur J Clin Pharmacol. 2020 Jul;76(7):929-937. doi: 10.1007/s00228-020-02863-7. Epub 2020 Apr 13.
To evaluate the penetration of levofloxacin and dexamethasone sodium phosphate into the aqueous humour (AH) after administration in combination and as single molecules. Evaluation of the penetration of those agents in the site of action and their pharmacodynamic potential activity in view of the intended clinical use after cataract surgery.
Randomised, assessor-blinded, parallel-group. Patients scheduled for cataract surgery were assigned in a 1:1:1 ratio to: levofloxacin + dexamethasone sodium phosphate (L-DSP), Levofloxacin (L) or Dexamethasone sodium phosphate (DSP) eye drops. Either test or reference drugs were instilled in the cul-de-sac twice, 90 and 60 min before paracentesis.
A total of 125 patients completed the study. Fraction of dose absorbed in the anterior chamber was 3.8-4.2 · 10 for levofloxacin and 0.3-0.4 · 10 for dexamethasone, respectively. No notable differences in concentration of levofloxacin were found between L-DSP arm (1.970 nmol/ml) and L arm (2.151 nmol/ml). The concentrations of levofloxacin were well above the MICs for the most frequent Gram-positive and Gram-negative eye pathogens. Dexamethasone concentrations were slightly lower in L-DSP arm (0.030 nmol/ml) than in DSP arm (0.042 nmol/ml), but still in the pharmacodynamically active range in the site of action. The difference was not clinically relevant. DSP was not detected in any HA sample, suggesting its full hydrolysis to free dexamethasone.
Our results confirm that no interaction is evident on the corneal penetration of levofloxacin and dexamethasone which reach pharmacologically active concentrations when instilled as fixed combination eye drops to patients undergoing cataract surgery.
ClinicalTrials.gov Identifier: NCT03740659.
评估左氧氟沙星和地塞米松磷酸钠联合给药及单独给药后在房水中的渗透情况。鉴于白内障手术后的预期临床应用，评估这些药物在作用部位的渗透情况及其药效学潜在活性。
随机、评估者盲法、平行组。计划进行白内障手术的患者按1:1:1的比例分配至：左氧氟沙星+地塞米松磷酸钠（L-DSP）、左氧氟沙星（L）或地塞米松磷酸钠（DSP）滴眼液组。在穿刺前90分钟和60分钟，将试验药物或对照药物滴入结膜囊两次。
共有125例患者完成研究。左氧氟沙星在前房吸收的剂量分数分别为3.8 - 4.2·10，地塞米松为0.3 - 0.4·10。L-DSP组（1.970 nmol/ml）和L组（2.151 nmol/ml）之间左氧氟沙星浓度无显著差异。左氧氟沙星浓度远高于最常见的革兰氏阳性和革兰氏阴性眼部病原体的最低抑菌浓度。L-DSP组地塞米松浓度（0.030 nmol/ml）略低于DSP组（0.042 nmol/ml），但仍处于作用部位的药效学活性范围内。差异无临床相关性。在任何房水样本中均未检测到DSP，表明其完全水解为游离地塞米松。
我们的结果证实，左氧氟沙星和地塞米松的角膜渗透没有明显相互作用，当作为固定组合滴眼液滴入白内障手术患者时，它们能达到药理活性浓度。
ClinicalTrials.gov标识符：NCT03740659。
