Department of Pharmaceutics, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, 110016, Liaoning Province, PR China.
Biopharm Drug Dispos. 2012 Jan;33(1):30-8. doi: 10.1002/bdd.1772. Epub 2012 Feb 8.
The effect of dosing time on the bioavailability of carbamazepine immediate-release (IR) tablets was investigated when administered to beagle dogs who were fasting, with co-administration of food (Co-food), and 0.5 h before food and 2 h after food. The study was conducted using a single dose of 200 mg (tablets/solution) with a 2 week washout period in a crossover design. Food intake significantly increased the rate and extent of tablet absorption. The C(max) (µg·ml⁻¹, 8.13/3.65) and t(max) (h, 1.83/0.92) were increased more than two-fold and the AUC₀₋₂₄ (µg·h·ml⁻¹, 20.09/8.19) was 2.5 times that of the values obtained under fasting conditions. The bioavailability of the tablets under fasting conditions was 91.2%, but increased to 223.5%, 182.8% and 148.4% in the Co-food, 0.5 h before food and 2 h after food groups, respectively (p < 0.05). Although there was no significant difference in the C(max) or AUC₀₋₂₄ between the treatments with food, the absorption appeared to be reduced to some extent when the tablets were given 2 h after food. The oral bioavailability of CBZ IR tablets was significantly affected by the timing of the food intake. This is maybe favored by the fluctuations in the level of bile salts with the timing of food intake. To obtain acute therapy for a drug with narrow therapeutic window, attention should be given to the dosing time and food intake interactions.
当给予禁食、与食物同时给予（Co-food）以及食物前 0.5 小时和食物后 2 小时的比格犬时，研究了给药时间对卡马西平速释（IR）片剂生物利用度的影响。该研究采用 200mg 单剂量（片剂/溶液），在交叉设计中具有 2 周洗脱期。食物摄入显著增加了片剂吸收的速率和程度。Cmax（µg·ml⁻¹，8.13/3.65）和 tmax（h，1.83/0.92）增加了两倍以上，AUC₀₋₂₄（µg·h·ml⁻¹，20.09/8.19）是禁食条件下获得的值的 2.5 倍。在禁食条件下，片剂的生物利用度为 91.2%，但在 Co-food、食物前 0.5 小时和食物后 2 小时组中分别增加到 223.5%、182.8%和 148.4%（p<0.05）。虽然食物处理之间的 Cmax 或 AUC₀₋₂₄ 没有显著差异，但当片剂在食物后 2 小时给予时，吸收似乎在某种程度上减少。卡马西平 IR 片剂的口服生物利用度受到食物摄入时间的显著影响。这也许是由于胆汁盐水平随食物摄入时间的波动而受到影响。为了获得狭窄治疗窗药物的急性治疗，应注意给药时间和食物摄入的相互作用。
