Tazawa K, Takemori S, Hirokawa S, Yamamoto K, Katsuki S, Arai H, Kasagi T, Katsuyama S, Fujimaki M
Second Department of Surgery, Toyama Medical and Pharmaceutical University, Japan.
Jpn J Surg. 1991 Nov;21(6):621-6. doi: 10.1007/BF02471046.
Two different preparations of commercially available suppositories containing Ketoprofen (KP) were administered to 49 patients immediately following anal surgery. The KP was prepared as either fatty suppositories (FS) or gelatin capsulated suppositories (GCS) and surgery was performed under either spinal (n = 37) or local anesthesia (n = 12). Similar results were observed in the kinetics of KP after both FS and GCS administration. The extent of bioavailability of the two dosage forms in the patient groups and control subjects (n = 10) were essentially equal. When the pharmacokinetic parameters of KP were compared between patient groups under spinal and local anesthesia, significant differences were found in the values of the peak level (C max), peak time (T max), and terminal phase half-life (t 1/2). The C max decreased by one-half, while the T max and t 1/2 increased twice and four times, respectively, in patient operated on under spinal anesthesia compared to those operated on under local anesthesia. The absorption rate constant (Ka) following spinal anesthesia was significantly less than that following local anesthesia or that of the healthy subjects (p less than 0.01). A "flip-flop" phenomena could be seen in the time profiles of plasma KP concentration following spinal anesthesia.
在49例患者肛门手术后，立即给予两种市售含酮洛芬（KP）的不同栓剂制剂。KP制备为脂肪栓剂（FS）或明胶胶囊栓剂（GCS），手术在脊髓麻醉（n = 37）或局部麻醉（n = 12）下进行。FS和GCS给药后KP的动力学观察到相似结果。两种剂型在患者组和对照组（n = 10）中的生物利用度程度基本相等。当比较脊髓麻醉和局部麻醉下患者组中KP的药代动力学参数时，发现峰浓度（Cmax）、达峰时间（Tmax）和终末相半衰期（t1/2）的值存在显著差异。与局部麻醉下手术的患者相比，脊髓麻醉下手术的患者Cmax降低一半，而Tmax和t1/2分别增加两倍和四倍。脊髓麻醉后的吸收速率常数（Ka）显著低于局部麻醉后或健康受试者的吸收速率常数（p小于0.01）。脊髓麻醉后血浆KP浓度的时间曲线中可观察到“翻转”现象。
