Bass J, Miles M V, Tennison M B, Holcombe B J, Thorn M D
Burroughs Wellcome, Research Triangle Park, North Carolina.
Epilepsia. 1989 May-Jun;30(3):364-9. doi: 10.1111/j.1528-1157.1989.tb05310.x.
In a randomized, two-period crossover clinical study, eight normal male volunteers received two separate 500-mg doses of carbamazepine (CBZ) suspension 1 week apart. One dose was administered orally after an overnight fast, and the other was administered by nasogastric feeding tube during a continuous enteral feeding infusion. Serial serum CBZ concentrations were determined by high-performance liquid chromatography (HPLC) to assess the effects of the enteral feeding on CBZ absorption. Noncompartmental methods were used to estimate pharmacokinetic data. One volunteer experienced a mild hypersensitivity reaction after his first CBZ dose and was withdrawn from the study. The other subjects tolerated both doses very well, although most experienced mild drowsiness or lightheadedness. Serum CBZ concentrations were lower during enteral feeding administration, but the differences were statistically significant only at 8 h (p = 0.044). Changes in pharmacokinetic data were not significant, although the decrease in maximum serum concentration approached significance (p = 0.052). The relative bioavailability of CBZ suspension with enteral feeding administration was 90.1% of that during fasting. There was a strong correlation between CBZ dose (mg/kg) and Cmax after oral administration (r = 0.97, Y = 1.88X - 4.49, p less than 0.001) but not during enteral feeding administration. Although absorption of CBZ suspension was generally slower and slightly diminished during nasogastric feeding, this interaction may lessen unwanted side effects.
在一项随机、两阶段交叉临床研究中,8名正常男性志愿者间隔1周分别接受了两剂500毫克的卡马西平(CBZ)混悬液。一剂在禁食过夜后口服,另一剂通过鼻胃饲管在持续肠内喂养输注期间给药。通过高效液相色谱法(HPLC)测定系列血清CBZ浓度,以评估肠内喂养对CBZ吸收的影响。采用非房室方法估算药代动力学数据。一名志愿者在首次服用CBZ后出现轻度过敏反应,退出了研究。其他受试者对两剂药物耐受性良好,尽管大多数人经历了轻度嗜睡或头晕。肠内喂养给药期间血清CBZ浓度较低,但差异仅在8小时时有统计学意义(p = 0.044)。药代动力学数据变化不显著,尽管最大血清浓度的降低接近显著水平(p = 0.052)。肠内喂养给药时CBZ混悬液的相对生物利用度为禁食期间的90.1%。口服给药后CBZ剂量(mg/kg)与Cmax之间存在强相关性(r = 0.97,Y = 1.88X - 4.49,p小于0.001),但在肠内喂养给药期间不存在。尽管在鼻胃喂养期间CBZ混悬液的吸收通常较慢且略有减少,但这种相互作用可能会减轻不良副作用。