Armogida Marianna, Gold Morris
Novartis Consumer Health, Switzerland.
Int J Clin Pharmacol Ther. 2012 Jun;50(6):445-51. doi: 10.5414/cp201658.
A new liquid capsule formulation of low-dose diclofenac-K in 12.5 mg and 25 mg dosages has been developed to provide the patient with an easier to swallow form than the current low-dose tablets. The new formulation is expected to have a faster rate of absorption and comparable overall bioavailability compared with the tablet formulations.
To compare the systemic bioavailability of diclofenac from the new 25 mg liquid capsule vs. the currently registered diclofenac-K 2 × 12.5 mg tablets, and to evaluate the safety of the 25 mg liquid capsule.
In this randomized, open-label, crossover, comparative bioavailability study, 42 healthy subjects (mean age 23.2 years) were given a single dose of diclofenac-K 25 mg liquid capsule or 2 × 12.5 mg tablets over 1-day treatment periods, separated by a washout period of 14 days.
The total systemic exposure to diclofenac, as measured by the mean AUCs, was equivalent between treatments. However, the geometric mean Cmax for the 25 mg liquid capsule was almost double that of 2 × 12.5 mg tablets (1,058.2 vs. 564.5 ng/ml), while the median tmax was 5 minutes faster with the 25 mg liquid capsule and the geometric mean AUCtmax ref for the 25 mg liquid capsule (133.0 ng×h/ml) was much higher than for 2 × 12.5 mg tablets (91.6 ng×h/ml). The estimated AUCtmax ref ratio of 25 mg liquid capsule to 2 × 12.5 mg tablets was 143.1%, indicating much higher early exposure to diclofenac from the 25 mg liquid capsule. Both formulations were very well tolerated and only one adverse event was considered drug related (headache after taking the diclofenac-K 25 mg liquid capsule).
Diclofenac-K 25 mg liquid capsule was equivalent to diclofenac-K 2 × 12.5 mg tablets in terms of overall systemic exposure to diclofenac. However, the rate of absorption of diclofenac was much faster from the liquid capsule than from the tablets, with a much greater early exposure to diclofenac. Both formulations were very well tolerated.
已研发出低剂量双氯芬酸钾的新型液囊制剂，剂量为12.5毫克和25毫克，旨在为患者提供比当前低剂量片剂更易吞咽的剂型。预计该新型制剂与片剂制剂相比，吸收速度更快，总体生物利用度相当。
比较新型25毫克液囊制剂与当前已注册的双氯芬酸钾2×12.5毫克片剂中双氯芬酸的全身生物利用度，并评估25毫克液囊制剂的安全性。
在这项随机、开放标签、交叉、比较生物利用度研究中，42名健康受试者（平均年龄23.2岁）在为期1天的治疗期内单次服用25毫克双氯芬酸钾液囊制剂或2×12.5毫克片剂，中间间隔14天的洗脱期。
通过平均药时曲线下面积测量，两种治疗方法中双氯芬酸的全身总暴露量相当。然而，25毫克液囊制剂的几何平均峰浓度几乎是2×12.5毫克片剂的两倍（1058.2对564.5纳克/毫升），而25毫克液囊制剂的中位达峰时间快5分钟，且25毫克液囊制剂的几何平均达峰时药时曲线下面积（133.0纳克·小时/毫升）远高于2×12.5毫克片剂（91.6纳克·小时/毫升）。25毫克液囊制剂与2×12.5毫克片剂的达峰时药时曲线下面积估计比值为143.1%，表明25毫克液囊制剂中双氯芬酸的早期暴露量高得多。两种制剂耐受性均良好，仅1例不良事件被认为与药物相关（服用25毫克双氯芬酸钾液囊制剂后出现头痛）。
就双氯芬酸的全身总体暴露量而言，25毫克双氯芬酸钾液囊制剂与2×12.5毫克双氯芬酸钾片剂相当。然而，液囊制剂中双氯芬酸的吸收速度比片剂快得多，双氯芬酸的早期暴露量也大得多。两种制剂耐受性均良好。
