Aim To develop a sensitive and accurate HPLC method for the determination of fleroxacin in human plasma, and study its pharmacokinetics in healthy subjects. Methods The analytes were isolated fi＇om plasma by simple p...Aim To develop a sensitive and accurate HPLC method for the determination of fleroxacin in human plasma, and study its pharmacokinetics in healthy subjects. Methods The analytes were isolated fi＇om plasma by simple protein precipitation with methanol, separated on a Diamonsil C18 column by isocratic elution with the mobile phase consisted of 1% triethylamine at pH 4.8 （adjusted with phosphoric acid） and acetonitrile （80/20, V/V） at a flow rate of 1.0 mL.min^-1 and analyzed by fluorescence detector with an excitation at 290 nm and emission 458 nm. The pharmacokinetic study of fleroxacin was performed according to a double period crossover design. Results The weighted （1/x） calibration curve was linear over the plasma concentration range of 0.025 - 8.00 μg.mL^-1 The inter- and intra-day precisions （RSD/%） were no more than 5.16%, and the method accuracies and extraction recoveries at three concentrations ranged firom 99.1% to 100.9%, and 86.7% to 92.0%, respectively. Following oral administration at a dose of 400 mg fleroxacin, the main pharmacokinetic parameters for test and reference capsules were Cmax5.08 ± 0.78 and 5.38 ± 1.40 μg.mL^-1, tmax 1.72 ±0.79 and 1.82 ± 0.78 h, t1/2 11.68 ± 1.27 and 11.38 ± 1.51 h^-1, AUC0-∞ 78.44 ± 11.44 and 76.53 ± 13.24 μg.mL^-1.h, respectively. Conclusion The method is sensitive and accurate, and suitable for human pharmacokinetic study of fleroxacin.展开更多
Aim To investigate the pharmacokinetics of levosimendan administered as intravenous injection in Chinese healthy volunteers. Methods Twelve subjects were randomly divided into three groups. Each subject in the group 1...Aim To investigate the pharmacokinetics of levosimendan administered as intravenous injection in Chinese healthy volunteers. Methods Twelve subjects were randomly divided into three groups. Each subject in the group 1 was administered at a single dose of 6 μg·kg^-1 levosimendan by intravenous bolus injection within 10 min, and then followed by intravenous infusion for 4 h at a dose per minute of 0.05 μg·kg^-1·min^-1. Similarly, each subject in the group 2 （or group 3） was given by intravenous bolus injection at a dose of 12 μg·kg^-1 （or 18 μg·kg^-1） followed by an infusion at a dose of 0.10 μg·kg^-1·min^-1 （or 0.15 μg·kg^-1·min^-1） levosimendan. Blood samples were collected at 0 （prior to dosing）, 0.17, 0.5, 1, 2, 3, 4, 4.25, 4.5, 4.75, 5, 5.5, 6, 7, 8 and 10 h after administrations. Levosimendan concentrations in plasma were measured by LC-MS/MS method. The pharmacokinetic parameters were calculated using a software Drug and Statistic （version 2.0）. Results After administrations of levosimendan at various dose levels, the half-life （t1/2） values were 1.50 ± 0.35, 1.64 ± 0.25 and 1.54 ± 0.39 h; the maximal concentrations after injections （Co） were 9.54 ± 3.90, 15.95 ± 7.84 and 28.46 ± 10.74 ng·mL^-1; the areas under concentration-time （AUCo-t （t=7.8）） were 33.63± 9.34,54.39 ± 15.34 and 78.36 ± 23.74 ng ·mL^-1·h, respectively. Conclusion The C0 and A UC0-tvalues of levosimendan exhibited a dose-dependent manner, respectively. No differences in the pharmacokinetic parameters were observed between male and female Chinese subjects.展开更多
Aim To assess the safety and tolerance of adefovir dipivoxil （ADV） in Chinese healthy volunteers. Methods A total of 52 healthy volunteers, 26 males and 26 females, aged from 19 to 26 were enrolled in the study. For...Aim To assess the safety and tolerance of adefovir dipivoxil （ADV） in Chinese healthy volunteers. Methods A total of 52 healthy volunteers, 26 males and 26 females, aged from 19 to 26 were enrolled in the study. Forty-two subjects were randomized into 5, 10, 20, 40, and 60 mg dose groups （6 - 10 subjects in each） matched by sex and weight for single-dose trial. Ten subjects were orally given 10 mg of ADV tablets once daily for 7 d for multiple-dose trial. Physical examination, vital signs examination, electrocardiography, type-B ultrasonography, chest fluoroscopy, routine blood test, routine urine test, coagulation tests, and blood biochemical test were conducted on schedule and statistically evaluated. Results Asthenia frequently occurred in multiple-dose trial, nausea, abdominal pain, and diarrhea occurred in both single- and multiple-dose trials. ALT, bilirubin, CK, and LDH were slightly elevated. All adverse reactions and laboratory abnormalities were mild, and the frequency and severity were not related to doses. Conclusion ADV is safe and well tolerated in Chinese healthy volunteers at dose of 5 - 60 mg oncedaily or 10 nag once daily for 7 d. The recommended oral dosage regimen is 10 mg once daily. Attention should be paid to renal and liver functions, CK, AMY and LDH, if we take ADV for a long period of time.展开更多
文摘Aim To develop a sensitive and accurate HPLC method for the determination of fleroxacin in human plasma, and study its pharmacokinetics in healthy subjects. Methods The analytes were isolated fi＇om plasma by simple protein precipitation with methanol, separated on a Diamonsil C18 column by isocratic elution with the mobile phase consisted of 1% triethylamine at pH 4.8 （adjusted with phosphoric acid） and acetonitrile （80/20, V/V） at a flow rate of 1.0 mL.min^-1 and analyzed by fluorescence detector with an excitation at 290 nm and emission 458 nm. The pharmacokinetic study of fleroxacin was performed according to a double period crossover design. Results The weighted （1/x） calibration curve was linear over the plasma concentration range of 0.025 - 8.00 μg.mL^-1 The inter- and intra-day precisions （RSD/%） were no more than 5.16%, and the method accuracies and extraction recoveries at three concentrations ranged firom 99.1% to 100.9%, and 86.7% to 92.0%, respectively. Following oral administration at a dose of 400 mg fleroxacin, the main pharmacokinetic parameters for test and reference capsules were Cmax5.08 ± 0.78 and 5.38 ± 1.40 μg.mL^-1, tmax 1.72 ±0.79 and 1.82 ± 0.78 h, t1/2 11.68 ± 1.27 and 11.38 ± 1.51 h^-1, AUC0-∞ 78.44 ± 11.44 and 76.53 ± 13.24 μg.mL^-1.h, respectively. Conclusion The method is sensitive and accurate, and suitable for human pharmacokinetic study of fleroxacin.
文摘Aim To investigate the pharmacokinetics of levosimendan administered as intravenous injection in Chinese healthy volunteers. Methods Twelve subjects were randomly divided into three groups. Each subject in the group 1 was administered at a single dose of 6 μg·kg^-1 levosimendan by intravenous bolus injection within 10 min, and then followed by intravenous infusion for 4 h at a dose per minute of 0.05 μg·kg^-1·min^-1. Similarly, each subject in the group 2 （or group 3） was given by intravenous bolus injection at a dose of 12 μg·kg^-1 （or 18 μg·kg^-1） followed by an infusion at a dose of 0.10 μg·kg^-1·min^-1 （or 0.15 μg·kg^-1·min^-1） levosimendan. Blood samples were collected at 0 （prior to dosing）, 0.17, 0.5, 1, 2, 3, 4, 4.25, 4.5, 4.75, 5, 5.5, 6, 7, 8 and 10 h after administrations. Levosimendan concentrations in plasma were measured by LC-MS/MS method. The pharmacokinetic parameters were calculated using a software Drug and Statistic （version 2.0）. Results After administrations of levosimendan at various dose levels, the half-life （t1/2） values were 1.50 ± 0.35, 1.64 ± 0.25 and 1.54 ± 0.39 h; the maximal concentrations after injections （Co） were 9.54 ± 3.90, 15.95 ± 7.84 and 28.46 ± 10.74 ng·mL^-1; the areas under concentration-time （AUCo-t （t=7.8）） were 33.63± 9.34,54.39 ± 15.34 and 78.36 ± 23.74 ng ·mL^-1·h, respectively. Conclusion The C0 and A UC0-tvalues of levosimendan exhibited a dose-dependent manner, respectively. No differences in the pharmacokinetic parameters were observed between male and female Chinese subjects.
文摘Aim To assess the safety and tolerance of adefovir dipivoxil （ADV） in Chinese healthy volunteers. Methods A total of 52 healthy volunteers, 26 males and 26 females, aged from 19 to 26 were enrolled in the study. Forty-two subjects were randomized into 5, 10, 20, 40, and 60 mg dose groups （6 - 10 subjects in each） matched by sex and weight for single-dose trial. Ten subjects were orally given 10 mg of ADV tablets once daily for 7 d for multiple-dose trial. Physical examination, vital signs examination, electrocardiography, type-B ultrasonography, chest fluoroscopy, routine blood test, routine urine test, coagulation tests, and blood biochemical test were conducted on schedule and statistically evaluated. Results Asthenia frequently occurred in multiple-dose trial, nausea, abdominal pain, and diarrhea occurred in both single- and multiple-dose trials. ALT, bilirubin, CK, and LDH were slightly elevated. All adverse reactions and laboratory abnormalities were mild, and the frequency and severity were not related to doses. Conclusion ADV is safe and well tolerated in Chinese healthy volunteers at dose of 5 - 60 mg oncedaily or 10 nag once daily for 7 d. The recommended oral dosage regimen is 10 mg once daily. Attention should be paid to renal and liver functions, CK, AMY and LDH, if we take ADV for a long period of time.
