Kanamoto I, Nakagawa T, Horikoshi I, Koizumi T, Tazawa K, Fujimaki M
Department of Hospital Pharmacy, Toyama Medical and Pharmaceutical University, Japan.
J Pharmacobiodyn. 1988 Mar;11(3):141-5. doi: 10.1248/bpb1978.11.141.
Two kinds of dosage forms of commercially available suppositories containing ketoprofen (KP), fatty suppositories (FS) and gelatin capsulated suppositories (GCS), were administered to patients immediately after anal surgery, and results obtained were compared. No difference was found in each corresponding pharmacokinetic parameter of the two dosage forms. However, when these parameters were compared with those from healthy subjects, significant differences were found in the values of peak level (Cmax), peak time (Tmax) and terminal phase half-life (t1/2). Cmax decreased by one half, and Tmax and t1/2 increased two and four times longer, respectively, those from healthy subjects. The absorption rate constant (ka) in patients was significantly (p less than 0.01) smaller than that in healthy subjects. However, the distribution volume/bioavailability (Vd/F), elimination rate constant (kel), and area under the curve (AUC) differed only slightly. Consequently, the flip-flop phenomena could be seen in the time profiles of plasma KP concentration of patients. These results suggested that the rectal suppository of KP should be administered with care, especially in the patients operated on under spinal anesthesia.
将两种市售含酮洛芬（KP）的栓剂剂型，即脂肪栓剂（FS）和明胶胶囊栓剂（GCS），在患者肛门手术后立即给药，并比较所得结果。两种剂型各自相应的药代动力学参数未发现差异。然而，当将这些参数与健康受试者的参数进行比较时，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。Cmax降低了一半，Tmax和t1/2分别比健康受试者延长了两倍和四倍。患者的吸收速率常数（ka）显著（p小于0.01）低于健康受试者。然而，分布容积/生物利用度（Vd/F）、消除速率常数（kel）和曲线下面积（AUC）仅略有差异。因此，在患者血浆KP浓度的时间曲线上可以看到反转现象。这些结果表明，KP直肠栓剂给药时应谨慎，尤其是在脊髓麻醉下接受手术的患者中。
