十二位志願者以單一口服方式服用三種不同劑量之Diphenidol，其排除半衰期（t1/2）分別各為5.95±3.23hr、6.29±0.3hr、7.36±3.06hr，經統計結果顯示其值並未因劑量增加而有所不同。將三個劑量所得之AUC及Cmax和劑量間做相關性的研究後，結果亦顯示此二參數均隨著劑量的增大呈線性增加，且劑量之高低與Tmax值大小並 無顯著差異。另外在建立體內動力學參數部分，十二位志願者以口服方式服用單一劑量25mg Diphenidol後，其AUC0~t 為562 ± 270 hr*ng/ml，Tmax 介於1.0和4 hr間，與國外文獻記載之數據1.5~3 hr相似。排除半衰期為6.29±2.16hr，此文獻記載 約4 hr稍長 ，也比Jos´e Herna´ndez.的研究報告上排除半衰期 3hr長約2倍。
由本研究結果所得Diphenidol於血中藥物濃度與口服藥物量呈線性動力學模式，因此在此線性範圍下，可根據劑量的變化來推算血中藥物濃度的改變程度。而本研究所得在台灣健康志願者所呈現之各項動力學參數數據，則可提供各臨床應用上之參考依據。 Background and Purpose: Diphenidol is an antiemtic agent in treatment of vomiting and vertigo. It has been reported to cause various adverse effects including hallucination, confusion and occasionally drowsiness. Since there was limited pharmacokinetic data of Diphenidol in the pervious literature, the purpose of our studies is to examine the pharmacokinetics of Diphenidol in Taiwanese subjects.
Methods: The relatiship between dose and pharmacokinetic parameter of Diphenidol was assessed in tweleve healthy Taiwanese after administration of single oral dose of 25, 50 and 75mg. A randomized balanced, parallel design was used. Moreover, in order to obtain pharmacokinetic parameters of Diphenidol in Taiwanese subjects, twelve healthy adult Taiwanese were randomized to receive a single dose of Diphenidol (25mg). Serial blood samples were taken up to 36 hr post-dose and plasma concentrations of Diphendol were determined by using LC/MS/MS.
Results: The linear pharmacokinetics behavior of Diphenidol was observed following oral administration of 25, 50, and 75 mg Diphenidol in Taiwanese subjects. The mean elimination half-life (t1/2) of Diphenidol were 5.95 ± 3.23,
6.29 ± 0.30 and 7.36 ± 3.06 hr for those doses, respectively. The peak plasma levels (Cmax) and the concentration-time curves (AUCs) data also showed dose-proportional response. The time to peak plasma concentration (Tmax) was similar regardless of the administered dose. Following oral administration of 25mg Diphenidol in tweleve Taiwanese subjects, the AUC0-∞ were 562 ± 270 hr*ng/ml and the Tmax were between 1 hr to 4 hr. The mean elimination half-life (t1/2) of Diphenidol were 6.29 ± 2.16 hr, which were higher than compared to the results obtained from Mexican population.
Conclusions: These findings suggest that the pharmacokinetic behavior of
Diphenidol is linear over the dose range studied. Pharmacokinetic parameters of
Diphenidol obtained in the present study can be utilized as reference for various clinical applications.