Westenberg H G, van der Kleijn E, Oei T T, de Zeeuw R A
Clin Pharmacol Ther. 1978 Mar;23(3):320-8. doi: 10.1002/cpt1978233320.
The concentration-time curves of carbamazepine (CBZ) and its metabolite (carbamazepine-10,11-epoxide; CBZ-epoxide) were determined in patients undergoing long-term antiepileptic drug treatment with the use of plasma and saliva data. Plasma and saliva samples were assayed concurrently for each patient by liquid chromatography. There was excellent linear correlation between CBZ levels in saliva and plasma (r = 0.991, p less than 0.001) over a large concentration range. The saliva/plasma ratio for CBZ concentration was 0.26 +/- 0.01 (SD). Since CBZ binding to plasma proteins is in the order of 76%, saliva CBZ concentration seems to reflect the unbound fraction of the drug in plasma. CBZ-epoxide has not been detected in saliva. The pharmacokinetic parameters of CBZ-epoxide were determined in 6 patients. The pharmacokinetic parameters of CBZ obtained from saliva concentrations were in excellent agreement with those obtained from plasma concentrations. Thus, CBZ determination in saliva is convenient for controlling blood levels in patients as well as for studying pharmacokinetics. The half-life, the relative body clearance of CBZ, and the metabolite concentration during steady-state, expressed as percent the parent compound, appear to be significantly different in patients on single and combined drug therapy.
利用血浆和唾液数据，测定了接受长期抗癫痫药物治疗患者的卡马西平（CBZ）及其代谢物（卡马西平-10,11-环氧化物；CBZ-环氧化物）的浓度-时间曲线。通过液相色谱法对每位患者的血浆和唾液样本进行同步检测。在较大浓度范围内，唾液和血浆中的CBZ水平之间存在极好的线性相关性（r = 0.991，p < 0.001）。CBZ浓度的唾液/血浆比值为0.26±0.01（标准差）。由于CBZ与血浆蛋白的结合率约为76%，唾液中CBZ浓度似乎反映了药物在血浆中的游离部分。在唾液中未检测到CBZ-环氧化物。在6名患者中测定了CBZ-环氧化物的药代动力学参数。从唾液浓度获得的CBZ药代动力学参数与从血浆浓度获得的参数非常一致。因此，测定唾液中的CBZ对于控制患者的血药水平以及研究药代动力学都很方便。在接受单一药物治疗和联合药物治疗的患者中，CBZ的半衰期、相对体内清除率以及稳态时代谢物浓度（以母体化合物的百分比表示）似乎有显著差异。
