Darwish Mona, Tempero Kenneth, Jiang John G, Simonson Philip G
Arch Drug Inf. 2008 Sep;1(2):56-62. doi: 10.1111/j.1753-5174.2008.00009.x.
Fentanyl buccal tablet (FBT; FENTORA(R), Cephalon, Inc., Frazer, PA, USA) is indicated in the US for breakthrough pain in patients with cancer who are already receiving and are tolerant to around-the-clock opioid therapy for underlying persistent cancer pain. For each individual patient, FBT should be titrated to the effective dose. OBJECTIVE: The primary objective was to characterize the pharmacokinetic parameters of FBT 400 microg administered as a single 400 microg tablet (regimen A) or as two 200 microg tablets given simultaneously (regimen B) and determine whether these are bioequivalent in healthy Japanese volunteers. Regimen C (two 200 microg tablets 30 minutes apart) was also compared as a secondary objective. METHODS: Healthy Japanese adults received regimens A, B, and C in a crossover fashion. Naltrexone was given to minimize the opioid effects of fentanyl. Serum fentanyl concentrations were determined in venous blood collected through 36 hours post dose. Regimens were declared bioequivalent with respect to bioavailability (as reflected by AUC(0-infinity), AUC(0-last), and C(max)) if the 90% confidence interval (CI) of the regimens' ratio fell within 0.80-1.25 (80%-125%). RESULTS: Twenty-nine volunteers (13 men, 16 women) were enrolled; 24 completed the study. Regimens A and B had bioequivalent systemic exposure parameters (B/A [90% CI]: AUC(0-infinity)108.4 [103.4, 113.7], AUC(0-last) 106.1 [100.7, 111.7], and C(max) 92.3 [83.2, 102.4]). Regimen C was bioequivalent to both A and B for AUCs, but only to B for C(max). Median time to C(max) was 45 minutes for regimen A and 60 minutes for regimens B and C. The most frequent AEs were dizziness, application-site erythema, headache, somnolence, nausea, and vomiting. All AEs were mild or moderate. CONCLUSIONS: Bioavailability of fentanyl after FBT 400 microg administered as a single tablet was bioequivalent to that after 2 simultaneously administered 200 microg tablets in healthy Japanese volunteers. AEs were mild or moderate.
芬太尼口腔崩解片（FBT；商品名FENTORA®，美国宾夕法尼亚州弗雷泽市Cephalon公司生产）在美国被批准用于已接受并耐受阿片类药物持续治疗基础癌痛的癌症患者的爆发性疼痛。对于每位患者，FBT应滴定至有效剂量。目的：主要目的是表征单次服用400μg FBT片剂（方案A）或同时服用两片200μg FBT片剂（方案B）的药代动力学参数，并确定在健康日本志愿者中这两种方案是否生物等效。作为次要目的，还比较了方案C（两片200μg FBT片剂间隔30分钟服用）。方法：健康日本成年人以交叉方式接受方案A、B和C。给予纳曲酮以尽量减少芬太尼的阿片样作用。在给药后36小时内采集静脉血，测定血清芬太尼浓度。如果两种方案的比值的90%置信区间（CI）在0.80 - 1.25（80% - 125%）内，则判定两种方案在生物利用度方面（以AUC(0 - ∞)、AUC(0 - last)和C(max)反映）生物等效。结果：招募了29名志愿者（13名男性，16名女性）；24名完成了研究。方案A和B具有生物等效的全身暴露参数（B/A [90% CI]：AUC(0 - ∞) 108.4 [103.4, 113.7]，AUC(0 - last) 106.1 [100.7, 111.7]，C(max) 92.3 [83.2, 102.4]）。方案C与方案A和B的AUC生物等效，但仅与方案B的C(max)生物等效。方案A达到C(max)的中位时间为45分钟，方案B和C为60分钟。最常见的不良事件为头晕、用药部位红斑、头痛、嗜睡、恶心和呕吐。所有不良事件均为轻度或中度。结论：在健康日本志愿者中，单次服用400μg FBT片剂后的芬太尼生物利用度与同时服用两片200μg FBT片剂后的生物利用度生物等效。不良事件为轻度或中度。
