Neuvonen P J
Int J Clin Pharmacol Ther Toxicol. 1985 Apr;23(4):226-32.
The bioavailability and central side effects of five carbamazepine tablets with different rates of absorption were investigated in nine healthy volunteers in a randomized cross-over study using single doses of 400 mg. There were seven-fold differences in the peak times (Tmax), 1.5-fold differences in the peak serum concentrations (Cmax) but no significant differences in the total bioavailability (AUC0-96 h) of these tablets. On the tablets with the slowest absorption the serum concentrations were still, 24 h after the ingestion, more than 90% of the Cmax. Central side effects (dizziness, ataxia) were significantly (p less than 0.01) more common when a brand of tablets with a rapid absorption was used. These tablets were characterized by a rapid dissolution in vitro in 0.1 N HCl. The total bioavailability of carbamazepine does not decrease despite moderate prolongation of the absorption phase. The pure AUC-data alone are inadequate to characterize the clinical equivalency of carbamazepine products. Formulations with a slow absorption may be preferable: central side effects are less common and serum concentrations more constant.
在一项随机交叉研究中，对9名健康志愿者单剂量服用400毫克的5种吸收速率不同的卡马西平片的生物利用度和中枢副作用进行了研究。这些片剂的达峰时间（Tmax）有7倍的差异，血药峰浓度（Cmax）有1.5倍的差异，但总生物利用度（AUC0 - 96小时）无显著差异。服用吸收最慢的片剂后，24小时时血清浓度仍超过Cmax的90%。使用吸收迅速的某品牌片剂时，中枢副作用（头晕、共济失调）显著更常见（p小于0.01）。这些片剂的特点是在体外0.1 N HCl中溶解迅速。尽管吸收期适度延长，但卡马西平的总生物利用度并未降低。仅靠单纯的AUC数据不足以表征卡马西平产品的临床等效性。吸收缓慢的制剂可能更可取：中枢副作用较少见，血清浓度更稳定。
