• YAKHAK HOEJI
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• v.51 no.2
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• pp.133-139
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• 2007

A simple and sensitive HPLC-MS method for quantitation of 10${\alpha}$-methoxy-9,10-dihydrolysergol (MDL), the main metabolite of nicergoline, in human plasma was developed and the bioavailability parameters of MDL was assessed in Korean healthy male volunteers. Clomipramine was used as an internal standard. MDL and internal standard in plasma sample were extracted using ethyl acetate. A centrifuged upper layer was then evaporated and reconstituted with mobile phase of 10 mM ammonium acetate-acetonitrile (10 : 90, v/v). The reconstituted samples were injected into a Zorbax SB-C8 column (2.1${\times}$150 mm,5 ${\mu}$m) at a flow-rate of 0.3 ml/min. Using MS with selected ion monitoring (SIM) mode, MDL and clomipramine were detected without severe interference from human plasma matrix. MDL produced a protonated molecular ion ([M+H]$^+$) at m/z 287. Internal standard produced a protonated molecular ion ([M+H]$^+$) at m/z 315. A linear relationship for MDL was found in the range of 2.5${\sim}$100 ng/ml. The lower limit of quantitation (LLOQ) was 2.5 ng/ml with acceptable precision and accuracy. The intra- and inter-day validation for all coefficients of variation (R.S.D.%) were found less than 15%. Main pharmacokinetic parameters of 30 mg of nicergoline were revealed as follows: AUC$_t$ 321.1${\pm}$64.5 ng${\cdot}$hr/ml, C$_{max}$, 51.2${\pm}$25.3 ng/ml, T$_{max}$ 3.6${\pm}$1.5 hr, K$_{el}$ 0.12${\pm}$0.07 hr$^{-1}$ and t$_{1/2}$ 7.6${\pm}$3.4 hr. Inter subject variations and race differences were shown in comparison with the published data in the literature.

• Health Policy and Management
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• v.21 no.2
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• pp.249-262
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• 2011

Since May 1st in 2008, the products of ginkgo biloba extract have had to be used with the patient's out-of-pocket payment due to reimbursement restriction guidelines. This study aims to analyze the policy effects of reimbursement restriction on pharmaceutical expenditures using interrupted time series(ITS) analysis. We retrieved monthly NHI claims data for the period between May, 2005 and December 2009. The ingredients identified as a substitute for ginkgo biloba have similar indications based on the similar pharmacological activities. The effects of changes in reimbursement scope were evaluated both for all relevant pharmaceuticals within the same therapeutic class and for 2 separate groups : ginkgo biloba's and its substitutes. According to the study results, restrictions on reimbursement scope resulted in savings of the drug expenditures in the targeted therapeutic class. Direct restriction on ginkgo biloba was associated with a decrease in expenditure level by 60.1% and changes in trend from an average increase rate of 1.4% to an average decrease rate of 1.5% for the therapeutic class, with a dramatic decrease in expenditure level(-191.5%) for ginkgo biloba itself, but with an increased expenditure level(+50.1%) and changes in trend from an average increase rate of 2.0% to an average decrease rate of 1.0% for the substitute group. Further policy to restrict nicergoline was associated with additional decrease in expenditure level for the therapeutic class. Additionally, we could identify the balloon effect - a new policy squeezing one part results in bulging out elsewhere. After the restriction of ginkgo biloba, the utilization of and expenditures on its substitutes increased significantly. In conclusion, we demonstrated that consecutively introduced policies effectively reduced overall expenditures on the therapeutic class of interest. Some ingredients played as a substitute while others did not. Further studies need to be conducted to identify which factors determine a substitute.