Aim To study the pharmacokinetics of oxiracetam after single and multipleintravenous administrations in healthy volunteers. Method A HPLC method was used to determine theserum concentration of oxiracetam after intrave...Aim To study the pharmacokinetics of oxiracetam after single and multipleintravenous administrations in healthy volunteers. Method A HPLC method was used to determine theserum concentration of oxiracetam after intravenous single dose and daily dose of 2 000 mg for 7 din ten Chinese healthy volunteers. Pharmacokinetic analysis was carried out using Drug And Statisticsoftware. Results The AUC_(0-12), AUC_(0-∞), K_e, t_(1/2), MRT after a single dose of 2 000 mgoxiracetam were 256.26 ± 16.84 μg·mL^(-1)·h, 276.74 ±18.11 μg·mL^(-1)·h, 0.18 ±0.03 h^(-1),3.84±0.64 h, and 4.39 10.39 h, and after multiple doses of oxiracetam were 259.36 ±25.43μg·mL^(-1)·h, 285.59 ±27.38 μg·mL^(-1)·h, 0.17 ±0.04 h^(-1), 4.14 ± 0.82 h, and 4.87 ±0.69 h, respectively. Conclusion The pharmacokinetic parameters of oxiracetam do not differremarkably after single and multiple intravenous administration and there is accumulation in serumafter 2 000 mg multiple intravenous administration once a day fof 7 d.展开更多
The intravenous formulation of levetiracetam (LEV)has been available in clinical practice worldwide for several years,but not in China.In the present study,we aimed to evaluate the bioequivalence of intravenous and or...The intravenous formulation of levetiracetam (LEV)has been available in clinical practice worldwide for several years,but not in China.In the present study,we aimed to evaluate the bioequivalence of intravenous and oral LEV (tablet), an antiepileptic drug,in healthy Chinese volunteers.Two randomized,single-dose (1500mg),open-label,2-period crossover trials were conducted as follows:study A,15-min infusion;study B,45-min infusion.A total of 22healthy men participated in study A,and 24healthy men and woman were enrolled in study B.In study A,blood samples were collected after termination of each treatment.In study B,samples were collected after oral or after the start of the intravenous administration.Safety and the ratio of intravenous/oral LEV for AUC 0-t and Cmax were evaluated.The 90% confidence intervals of Cmax and AUC0-t ratios for LEV 1500-mg tablets versus 15-min intravenous administration were outside the bioequivalence limits (80.00%-125.00%). For LEV 45-min intravenous administration,bioequivalence versus 1500-mg tablets was within the range for Cmax and AUC 0-t. The most frequently adverse event (AE)was somnolence.A total of eight subjects experienced nine mild AEs in study A, and 19subjects experienced 29mild AEs in study B.Intravenous infusions (15 and 45 min)of 1500-mg LEV were as well tolerated as the oral tablet.Bioequivalence was demonstrated by 45-min infusions.Therefore,direct conversion from oral to intravenous LEV 1500 mg (45-min infusion),or vice versa,was possible.展开更多
In the present study, we aimed to investigate the optimal dosage regimens of piperacillin/tazobactam in patients with chronic kidney disease according to their different classes of renal function based on bacterial re...In the present study, we aimed to investigate the optimal dosage regimens of piperacillin/tazobactam in patients with chronic kidney disease according to their different classes of renal function based on bacterial resistance. A total of 2700 simulationswere applied based on a published population pharmacokinetic and pharmacodynamic model using nonlinear mixed effects modeling (NONMEM) software. Permissible optimal dosage regimens were defined as those associated with a less than 10% of patients whose probabilities of target attainment (PTA) were not attain target. For patients with mild to moderate renal injury, 4/0.5 g of piperacillin/tazobactam every 12 h in 30 min intermittent infusion could attain the target. If the MIC (minimum inhibitory concentration) for the pathogen was 8 mg/L or 16 mg/L, either an 8-h or 6-h dosing interval or extended 2–6 h infusion regimen had to be used to achieve the outcome of the therapy. Regarding MIC was up to above 32 mg/L, a high dose of piperacillin (12–24 g/d) in continuous infusion was the only approach that could achieve the effective target in patients with renal dysfunction. A low dose with extended 4–6 h infusion regimen was recommended for patients with severe renal injury. Our study identified permissible optimal piperacillin/tazobactam dosage regimens for patients with renal dysfunction with an MIC up to 64 mg/L. The findings of this study would be helpful for precise administration of piperacillin/tazobactam in clinical practice.展开更多
文摘Aim To study the pharmacokinetics of oxiracetam after single and multipleintravenous administrations in healthy volunteers. Method A HPLC method was used to determine theserum concentration of oxiracetam after intravenous single dose and daily dose of 2 000 mg for 7 din ten Chinese healthy volunteers. Pharmacokinetic analysis was carried out using Drug And Statisticsoftware. Results The AUC_(0-12), AUC_(0-∞), K_e, t_(1/2), MRT after a single dose of 2 000 mgoxiracetam were 256.26 ± 16.84 μg·mL^(-1)·h, 276.74 ±18.11 μg·mL^(-1)·h, 0.18 ±0.03 h^(-1),3.84±0.64 h, and 4.39 10.39 h, and after multiple doses of oxiracetam were 259.36 ±25.43μg·mL^(-1)·h, 285.59 ±27.38 μg·mL^(-1)·h, 0.17 ±0.04 h^(-1), 4.14 ± 0.82 h, and 4.87 ±0.69 h, respectively. Conclusion The pharmacokinetic parameters of oxiracetam do not differremarkably after single and multiple intravenous administration and there is accumulation in serumafter 2 000 mg multiple intravenous administration once a day fof 7 d.
文摘The intravenous formulation of levetiracetam (LEV)has been available in clinical practice worldwide for several years,but not in China.In the present study,we aimed to evaluate the bioequivalence of intravenous and oral LEV (tablet), an antiepileptic drug,in healthy Chinese volunteers.Two randomized,single-dose (1500mg),open-label,2-period crossover trials were conducted as follows:study A,15-min infusion;study B,45-min infusion.A total of 22healthy men participated in study A,and 24healthy men and woman were enrolled in study B.In study A,blood samples were collected after termination of each treatment.In study B,samples were collected after oral or after the start of the intravenous administration.Safety and the ratio of intravenous/oral LEV for AUC 0-t and Cmax were evaluated.The 90% confidence intervals of Cmax and AUC0-t ratios for LEV 1500-mg tablets versus 15-min intravenous administration were outside the bioequivalence limits (80.00%-125.00%). For LEV 45-min intravenous administration,bioequivalence versus 1500-mg tablets was within the range for Cmax and AUC 0-t. The most frequently adverse event (AE)was somnolence.A total of eight subjects experienced nine mild AEs in study A, and 19subjects experienced 29mild AEs in study B.Intravenous infusions (15 and 45 min)of 1500-mg LEV were as well tolerated as the oral tablet.Bioequivalence was demonstrated by 45-min infusions.Therefore,direct conversion from oral to intravenous LEV 1500 mg (45-min infusion),or vice versa,was possible.
基金Peking University Third Hospital research funding(Grant No.7476-01)
文摘In the present study, we aimed to investigate the optimal dosage regimens of piperacillin/tazobactam in patients with chronic kidney disease according to their different classes of renal function based on bacterial resistance. A total of 2700 simulationswere applied based on a published population pharmacokinetic and pharmacodynamic model using nonlinear mixed effects modeling (NONMEM) software. Permissible optimal dosage regimens were defined as those associated with a less than 10% of patients whose probabilities of target attainment (PTA) were not attain target. For patients with mild to moderate renal injury, 4/0.5 g of piperacillin/tazobactam every 12 h in 30 min intermittent infusion could attain the target. If the MIC (minimum inhibitory concentration) for the pathogen was 8 mg/L or 16 mg/L, either an 8-h or 6-h dosing interval or extended 2–6 h infusion regimen had to be used to achieve the outcome of the therapy. Regarding MIC was up to above 32 mg/L, a high dose of piperacillin (12–24 g/d) in continuous infusion was the only approach that could achieve the effective target in patients with renal dysfunction. A low dose with extended 4–6 h infusion regimen was recommended for patients with severe renal injury. Our study identified permissible optimal piperacillin/tazobactam dosage regimens for patients with renal dysfunction with an MIC up to 64 mg/L. The findings of this study would be helpful for precise administration of piperacillin/tazobactam in clinical practice.
