Vetulani J, Melzacka M, Adamus A, Danek L
Arch Int Pharmacodyn Ther. 1983 Oct;265(2):180-91.
The pharmacokinetics of morphine were studied in various tissues of rats subjected to a single dose treatment (SDT, 30 mg/kg), constant dose treatment (CDT, 30 mg/kg daily for 8 days) and increasing dose treatment (IDT, twice daily, raising from an initial dose 20 mg/kg to the final 300 mg/kg). After CDT the elimination of morphine was slow and the drug was present in tissues in detectable amounts for over 24 hr, the area under the curve (AUC) values in the central nervous system increased significantly as compared with SDT. After IDT the elimination of morphine was rapid and the AUC values were decreased several times; in most of the tissues no detectable amount of morphine was present 24 hr after the last dose. The data indicate that morphine pharmacokinetics change after chronic treatment and depend on dosage schedule and that plasma concentration of morphine may not reflect the drug level in tissues, particularly in the central nervous system.
在接受单次剂量治疗（SDT，30毫克/千克）、恒定剂量治疗（CDT，每日30毫克/千克，持续8天）和递增剂量治疗（IDT，每日两次，初始剂量20毫克/千克，最终剂量300毫克/千克）的大鼠的各种组织中研究了吗啡的药代动力学。CDT后，吗啡的消除缓慢，药物在组织中可检测量存在超过24小时，与SDT相比，中枢神经系统中的曲线下面积（AUC）值显著增加。IDT后，吗啡的消除迅速，AUC值下降了几倍；在大多数组织中，最后一剂后24小时未检测到吗啡。数据表明，慢性治疗后吗啡药代动力学发生变化，取决于给药方案，并且吗啡的血浆浓度可能无法反映组织中的药物水平，特别是在中枢神经系统中。
