• Toxicological Research
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• v.21 no.4
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• pp.319-323
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• 2005

The aim of the present study was to evaluate systemic bioavailability of surfactin and to determine its pharmacokinetic profiles. The stability of surfactin to pH, temperature and protease was evaluated. Surfactin was resistant to high temperature, a wide range of pH and the action of hydrolytic enzymes. The pharmacokinetic natures of surfactin which were shown the short half-life, rapid clearance and poor bioavailability. The results of study should provide preliminary data of surfactin for further dose-finding studies and for the design of application forms. It is also be important to a context of the safety of surfactin.

• Biomolecules & Therapeutics
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• v.3 no.2
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• pp.97-103
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• 1995

The purpose of this study was to determine pharmacokinetic parameters of BR-28702-2, a new antineoplastic agent which is the conjugate of nucleotide and phospholipid, and to compare them with those of ara-C. Male rats were cannulated in the left femoral vein and received a single i.v. bolus dose of either BR-28702-2 or ara-C. BR-28702-2 was also administered i.p. and plasma samples were analyzed by reversedphase HPLC. The t$_{1}$2($\beta$)/ of ara-C(1.22 hr.) was significantly smaller than that of BR-28702-2(4.420 hr.). The absolute bioavailability of BR-28702-2 after i.p. injection was 1.125%. This lower bioavailability, together with previous reports that marked antineoplastic activity was observed when given i.p., indicates that BR-28702-2 would act as a depot system to release active moieties. Further works, therefore, need to be done to characterize active metabolites.

• Journal of Pharmaceutical Investigation
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• v.27 no.4
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• pp.323-329
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• 1997

Ipriflavone is non-hormonal antiosteoporotic drug which inhibits bone resorption by reducing recruitment and/or differentiation of osteoclasts, and stimulates proliferation and differentiation of osteoblast, and also enhances calcitonin secretion in the presence of estrogen. Although some kinds of immediately-released preparation of ipriflavone are available in commercial market, in present study, we tried to formulate sustained-release tablet using coating method with hydrophobic and hydrophilic coating materials. In vitro dissolution test was applied to evaluate sustained-release patterns of several test preparations (Test tablet A, B and C) designed using different preparation method or different compositions. From the results of dissolution test, test tablet A which showed suitable dissolution profile was selected as the candidate of new product. Pharmacokinetic evaluation of test drug, ipriflavone sustained-release tablets, was conducted in 6 beagle dogs weighing $11.5{\pm}0.5\;Kg$ compared with $Theobon^{\circledR}$ tablet, immediately-released tablet (Kukjae Pharm. Co.) as reference drug. Two products were randomly administered to 6 beagle dogs, and after 1 week, cross-over study was conducted. From the present study, AUC and $T_{max}$ of test product were significantly different from those of reference product (p<0.05), respectively$(AUC\;:\;3646.28{\pm}472.56\;vs\;3646.28{\pm}472.56\;ng{\cdot}hr/ml,\;T_{max}\;:\;4.33{\pm}1.03\;vs\;1.42{\pm}0.38\;hr)$. But $C_{max}$ was not significantly different between two products (p>0.05) $(\;512.52{\pm}48.18\;vs\;443.97{\pm}140.53\;ng/ml)$. From the results of pharmacokinetic evaluations, it was noted that absorption amount of test product was increased, but absorption rate was delayed and $C_{max}$ of two products were not changed. And it was concluded that redesign of the sustained-release preparation which has a lower content of iprifavone rather than test tablet A must be considered.

• Journal of Pharmaceutical Investigation
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• v.35 no.6
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• pp.437-443
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• 2005

A rapid, selective and sensitive reversed-phase HPLC method for the determination of a major metabolite of terfenadine, fexofenadine, in human serum was developed, validated, and applied to the pharmacokinetic study of terfenadine. Fexofenadine and internal standard, haloperidol were extracted from human serum by liquid-liquid extraction with acetonitrile and analyzed on a $Symmetry^{TM}$ C8 column with the mobile phase of 1% triethylamine phosphate (pH 3.7)-acetonitrile (67:33, v/v, adjusted to pH 5.6 with triethylamine). Detection wavelength of 230 nm for excitation, 280 nm for emission and flow rate of 1.0 mL/min were fixed for the study. The assay robustness for the changes of mobile phase pH, organic solvent content, and flow rate was confirmed by $3^{3}$ factorial design using a fixed fexofenadine concentration (50 ng/mL) with respect to its peak area and retention time. In addition, the ruggedness of this method was investigated at three different laboratories using same quality control (QC) samples. This method showed linear response over the concentration range of 10-500 ng/mL with correlation coefficients greater than 0.999. The lower limit of quantification using 0.5 mL of serum was 10 ng/mL, which was sensitive enough for the pharmacokinetic studies of terfenadine. The overall accuracy of the quality control samples ranged from 95.70 to 114.58% for fexofenadine with overall precision (% C.V.) being 3.53-14.39%. The relative mean recovery of fexofenadine for human serum was 90.17%. Stability studies (freeze-thaw, short-term, extracted serum sample and stock solution) showed that fexofenadine was stable during storage, or during the assay procedure in human serum. However, the storage at $-70^{\circ}C$ for 4 weeks showed that fexofenadine was not stable. The peak area and retention time of fexofenadine were not significantly affected by the changes of mobile phase pH, organic solvent content, and flow rate under the conditions studied. This method showed good ruggedness (within 15% C.V.) and was successfully used for the analysis of fexofenadine in human serum samples for the pharmacokinetic studies of orally administered Tafedine tablet (60 mg as terfenadine) at three different laboratories, demonstrating the suitability of the method.

• Journal of Pharmaceutical Investigation
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• v.35 no.4
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• pp.265-271
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• 2005

A rapid, selective and sensitive reversed-phase HPLC method for the determination of etodolac in human serum was developed, validated, and applied to the pharmacokinetic study of etodolac. Etodolac and internal standard, ibuprofen were extracted from human serum by liquid-liquid extraction with hexane/isopropanol (95:5, v/v) and analyzed on a Luna C18(2) column with the mobile phase of 1% aqueous acetic acid-acetonitrile (4:6, v/v). Detection wavelength of 227 nm and flow rate of 1.0 mL/min were fixed for the study. The assay robustness for the changes of mobile phase pH, organic solvent content, and flow rate was confirmed by $3^3$ factorial design using a fixed etodolac concentration $(1\;{\mu}g/mL)$ with respect to its peak area and retention time. And also, the ruggedness of this method was investigated at three different laboratories using same quality control (QC) samples. This method showed linear response over the concentration range of $0.05-40\;{\mu}g/mL$ with correlation coefficients greater than 0.999. The lower limit of quantification using 0.5 mL of serum was 0.05 ${\mu}g/mL$, which was sensitive enough for pharmacokinetic studies. The overall accuracy of the quality control samples ranged from 92.00 to 110.00% for etodolac with overall precision (% C.V.) being 1.08-10.11%. The percent recovery for human serum was in the range of 76.73-115.30%. Stability studies showed that etodolac was stable during storage, or during the assay procedure in human serum. The peak area and retention time of etodolac were not significantly affected by the changes of mobile phase pH, organic solvent content, and flow rate under the conditions studied. This method showed good ruggedness (within 15% C.V.) and was successfully used for the analysis of etodolac in human serum samples for the pharmacokinetic studies of orally administered Lodin XL tablet (400 mg as etodolac) at three different laboratories, demonstrating the suitability of the method.

• Journal of Pharmaceutical Investigation
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• v.35 no.6
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• pp.423-429
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• 2005

A selective and sensitive reversed-phase HPLC method for the determination of fenoprofen in human serum was developed, validated, and applied to the pharmacokinetic study of fenoprofen calcium. Fenoprofen and internal standard, ketoprofen, were extracted from human serum by liquid-liquid extraction with diethyl ether and analyzed on a Luna C18(2) column with the mobile phase of acetonitrile-3 mM potassium dihydrogen phosphate (32:68, v/v, adjusted to pH 6.6 with phosphoric acid). Detection wavelength of 272 nm and flow rate of 0.25 mL/min were fixed for the study. The assay robustness for the changes of mobile phase pH, organic solvent content, and flow rate was confirmed by $3^{3}$ factorial design using a fixed fenoprofen concentration $(2\;{\mu}g/mL)$ with respect to its peak area and retention time. And also, the ruggedness of this method was investigated at three different laboratories using same quality control (QC) samples. This method showed linear response over the concentration range of $0.05-100\;{\mu}g/mL$ with correlation coefficients greater than 0.999. The lower limit of quantification using 1 mL of serum was $0.05\;{\mu}g/mL$, which was sensitive enough for pharmacokinetic studies. The overall accuracy of the quality control samples ranged from 92.27 to 109.20% for fenoprofen with overall precision (% C.V.) being 5.51-11.71 %. The relative mean recovery of fenoprofen for human serum was 81.7%. Stability (freeze-thaw, short and long-term) studies showed that fenoprofen was not stable during storage. But, extracted serum sample and stock solution were allowed to stand at ambient temperature for 12 hr prior to injection without affecting the quantification. The peak area and retention time of fenoprofen were not significantly affected by the changes of mobile phase pH, organic solvent content, and flow rate under the conditions studied. This method showed good ruggedness (within 15% C.V.) and was successfully used for the analysis of fenoprofen in human serum samples for the pharmacokinetic studies of orally administered Fenopron tablet (600 mg as fenoprofen) at three different laboratories, demonstrating the suitability of the method.

• Journal of Pharmaceutical Investigation
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• v.36 no.2
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• pp.89-95
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• 2006

A selective and sensitive reversed-phase HPLC method for the determination of pentoxifylline in human serum was developed, validated, and applied to the pharmacokinetic study of pentoxifylline. Pentoxifylline and internal standard, chloramphenicol, were extracted from the serum by liquid-liquid extraction with dichloromethane and analyzed on a Luna CI8(2) column with the mobile phase of acetonitrile-0.034 M phosphoric acid (25:75, v/v, adjusted to pH 4.0 with 10 M NaOH). Detection wavelength of 273 nm and flow rate of 0.8 mL/min were used. This method showed linear response over the concentration range of 10-500 ng/mL with correlation coefficients greater than 0.999. The lower limit of quantification using 0.5 mL of the serum was 10 ng/mL, which was sensitive enough for pharmacokinetic studies of pentoxifylline. The overall accuracy of the quality control samples ranged from 89.3 to 92.7% for pentoxifylline with overall precision (% C.V.) being 4.1-9.2%. The relative mean recovery of pentoxifylline for human serum was 105.8%. Stability (stock solution, short and long-term) studies showed that pentoxifylline was not stable during storage. But three freeze-thaw cycles and extracted serum samples were stable. This method showed good ruggedness (within 15% C.V.) and was successfully applied for the analysis of pentoxifylline in human serum samples for the pharmacokinetic studies of orally administered $Trental^{\circledR}$ tablet (400 mg pentoxifylline), demonstrating the suitability of the method.

• Journal of Pharmaceutical Investigation
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• v.36 no.1
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• pp.45-51
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• 2006

A rapid, selective and sensitive reversed-phase HPLC method for the determination of dipyridamole in human serum was developed, validated, and applied to the pharmacokinetic study of dipyridamole. Dipyridamole and internal standard, loxapine, were extracted from human serum by liquid-liquid extraction with diethyl ether and analyzed on a Nova Pak $C_{I8}$ column with the mobile phase of 40 mM ammonium acetate:methanol:acetonitrile (35:35:30)(v/v/v, pH 7.8). Detection wavelength of 280 nm and flow rate of 1.0 mL/min were fixed for the study. The assay robustness for the changes of mobile phase pH, organic solvent content, and flow rate was confirmed by $3^3$ factorial design using a fixed dipyridamole concentration (50 ng/mL) with respect to its peak area and retention time. And also, the ruggedness of this method was investigated at three different laboratories using same quality control (QC) samples. This method showed linear response over the concentration range of 2-2000 ng/mL with correlation coefficients greater than 0.999. The lower limit of quantification using 0.5 mL of serum was 2 ng/mL, which was sensitive enough for pharmacokinetic studies of dipyridamole. The overall accuracy of the quality control samples ranged from 103.94 to 105.86% for dipyridamole with overall precision (% C.V.) being 4.60-11.49%. The relative mean recovery of dipyridamole for human serum was 97.64%. Stability studies showed that dipyridamole was stable during storage, or during the assay procedure in human serum. The peak area and retention time of dipyridamole were not significantly affected by the changes of mobile phase pH, organic solvent content, and flow rate under the conditions studied. This method showed good ruggedness (within 15% C.V.) and was successfully used for the analysis of dipyridamole in human serum samples for the pharmacokinetic studies of orally administered Dimor tablet (75 mg as dipyridamole) at three different laboratories, demonstrating the suitability of the method.

• Journal of Pharmaceutical Investigation
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• v.36 no.1
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• pp.23-29
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• 2006

A rapid, selective and sensitive reversed-phase HPLC method for the determination of promethazine in human serum was developed, validated, and applied to the pharmacokinetic study of promethazine. Promethazine and internal standard, chlorpromazine, were extracted from human serum by liquid-liquid extraction with n-hexane containing 0.8% isopropanol and analyzed on a Capcell Pak CN column with the mobile phase of acetonitrile-0.2 M potassium dihydrogen phosphate (42:58, v/v, adjusted to pH 6.0 with 1 M NaOH). Detection wavelength of 251 nm and flow rate of 0.9 mL/min were fixed for the study. The assay robustness for the changes of mobile phase pH, organic solvent content, and flow rate was confirmed by $3^{3}$ factorial design using a fixed promethazine concentration (10 ng/mL) with respect to its peak area and retention time. In addition, the ruggedness of this method was investigated at three different laboratories using same quality control (QC) samples. This method showed linear response over the concentration range of 1-40 ng/mL with correlation coefficients greater than 0.999. The lower limit of quantification using 1 mL of serum was 1 ng/mL, which was sensitive enough for pharmacokinetic studies. The overall accuracy of the quality control samples ranged from 96.15 to 105.40% for promethazine with overall precision (% C.V.) being 6.70-11.22%. The relative mean recovery of promethazine for human serum was 63.54%. Stability (freeze-thaw and short-term) studies showed that promethazine was stable during storage, or during the assay procedure in human serum. However, the storage at $-80^{\circ}C$ for 4 weeks showed that promethazine was not stable. Extracted serum sample and stock solution were not allowed to stand at ambient temperature for 12 hr prior to injection. The peak area and retention time of promethazine were not significantly affected by the changes of mobile phase pH, organic solvent content, and flow rate under the conditions studied. This method showed good ruggedness (within 15% C.V.) and was successfully used for the analysis of promethazine in human serum samples for the pharmacokinetic studies of orally administered Himazin tablet (25 mg as promethazine hydrochloride) at three different laboratories, demonstrating the suitability of the method.

• 한국약용작물학회:학술대회논문집
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• 2008.11a
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• pp.433-434
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• 2008