Adusumalli V E, Gilchrist J R, Wichmann J K, Kucharczyk N, Sofia R D
Department of Biochemistry, Wallace Laboratories, Cranbury, New Jersey 08512.
Epilepsia. 1992 Sep-Oct;33(5):955-60. doi: 10.1111/j.1528-1157.1992.tb02206.x.
The relative bioavailability and pharmacokinetics of felbamate (FBM) after a single oral dose and after 10 once-daily oral doses of 60 mg/kg were investigated in adult and pediatric dogs of both sexes. The pediatric and adult dogs were aged 4-6 weeks and 1-2 years, respectively. Analysis of variance (ANOVA) was performed on the bioavailability parameters among all groups and between the first and last doses. No sex-related differences in bioavailability and pharmacokinetic parameters were observed. The bioavailability of FBM in pediatric dogs was significantly less as compared with that in adult dogs. Rapid overall elimination of the drug in pediatric dogs appears to be responsible for the lower bioavailability. The bioavailability of FBM after the last dose was also significantly lower than after the first dose for both age groups. No major differences in the rate constant of FBM absorption (ka) and volume of distribution at steady state (VSS) were observed between the two age groups. As with other clinically useful antiepileptic drugs (AEDs), higher doses of FBM may be required in pediatric populations to achieve optimum drug levels, assuming that age-related changes in FBM disposition will also be confirmed in humans.
在成年和幼年雄性及雌性犬中，研究了单次口服剂量以及每日一次口服10剂60mg/kg非氨酯（FBM）后的相对生物利用度和药代动力学。幼年犬和成年犬的年龄分别为4 - 6周和1 - 2岁。对所有组之间以及首剂和末剂之间的生物利用度参数进行方差分析（ANOVA）。未观察到生物利用度和药代动力学参数存在性别相关差异。与成年犬相比，幼年犬中FBM的生物利用度显著降低。幼年犬中药物的快速整体消除似乎是生物利用度较低的原因。两个年龄组末次给药后FBM的生物利用度也显著低于首次给药后。两个年龄组之间在FBM吸收速率常数（ka）和稳态分布容积（VSS）方面未观察到重大差异。与其他临床有用的抗癫痫药物（AEDs）一样，假设FBM处置的年龄相关变化在人类中也得到证实，那么在儿科人群中可能需要更高剂量的FBM以达到最佳药物水平。
