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Akira Hishida - One of the best experts on this subject based on the ideXlab platform.
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Pharmacokinetics of Panipenem/betamipron in patients with end-stage renal disease
Journal of Infection and Chemotherapy, 2005Co-Authors: Naro Ohashi, Toshihiko Uematsu, Satoru Nagashima, Mitsutaka Kanamaru, Naoyuki Tajima, Akashi Togawa, Akira HishidaAbstract:Panipenem/betamipron (Carbenin), a parenteral carbapenem antibiotic, is used for the treatment of severe and intractable bacterial infections caused by gram-positive and gram-negative bacteria. Because 30% of Panipenem and most of the betamipron are excreted in the urine in an unchanged form, renal function is the important determinant of the dosage regimen of Panipenem/betamipron. In this study, the pharmacokinetics of Panipenem/betamipron were investigated in patients with end-stage renal disease (ESRD) undergoing hemodialysis treatment to establish an appropriate dose regimen. We further attempted to predict the in vivo clearance in patients undergoing hemodialysis based on the in vitro dializability. The pharmacokinetics of Panipenem/betamipron were investigated in eight patients after a 1-h intravenous infusion of Panipenem/betamipron (500 mg/500 mg). The in vitro extraction ratios of Panipenem/betamipron through a high-flux dialyzer were obtained, and compared with those obtained in vivo. The clearances of Panipenem in patients were 9.53 ± 1.26 l/h with hemodialysis, and 2.92 ± 0.238 l/h without hemodialysis. In contrast, those of betamipron were 4.18 ± 0.643 l/h and 0.615 ± 0.511 l/h, respectively. The clearance of Panipenem with hemodialysis were predicted well from in vitro extraction ratios, while that of betamipron was overestimated about 1.4-fold, probably due to high plasma protein binding and the binding difference between patients and healthy subjects. After comparing the pharmacokinetic behavior of Panipenem in patients with ESRD and that of a surrogate marker of efficacy, we recommend that these patients be treated with 500 mg/500 mg of Panipenem/betamipron once daily, which gives a similar clinical result in a patient with normal renal function.
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pharmacokinetics of Panipenem betamipron in patients with end stage renal disease
Journal of Infection and Chemotherapy, 2005Co-Authors: Naro Ohashi, Toshihiko Uematsu, Satoru Nagashima, Mitsutaka Kanamaru, Naoyuki Tajima, Akashi Togawa, Akira HishidaAbstract:Panipenem/betamipron (Carbenin), a parenteral carbapenem antibiotic, is used for the treatment of severe and intractable bacterial infections caused by gram-positive and gram-negative bacteria. Because 30% of Panipenem and most of the betamipron are excreted in the urine in an unchanged form, renal function is the important determinant of the dosage regimen of Panipenem/betamipron. In this study, the pharmacokinetics of Panipenem/betamipron were investigated in patients with end-stage renal disease (ESRD) undergoing hemodialysis treatment to establish an appropriate dose regimen. We further attempted to predict the in vivo clearance in patients undergoing hemodialysis based on the in vitro dializability. The pharmacokinetics of Panipenem/betamipron were investigated in eight patients after a 1-h intravenous infusion of Panipenem/betamipron (500 mg/500 mg). The in vitro extraction ratios of Panipenem/betamipron through a high-flux dialyzer were obtained, and compared with those obtained in vivo. The clearances of Panipenem in patients were 9.53 ± 1.26 l/h with hemodialysis, and 2.92 ± 0.238 l/h without hemodialysis. In contrast, those of betamipron were 4.18 ± 0.643 l/h and 0.615 ± 0.511 l/h, respectively. The clearance of Panipenem with hemodialysis were predicted well from in vitro extraction ratios, while that of betamipron was overestimated about 1.4-fold, probably due to high plasma protein binding and the binding difference between patients and healthy subjects. After comparing the pharmacokinetic behavior of Panipenem in patients with ESRD and that of a surrogate marker of efficacy, we recommend that these patients be treated with 500 mg/500 mg of Panipenem/betamipron once daily, which gives a similar clinical result in a patient with normal renal function.
Naoyuki Tajima - One of the best experts on this subject based on the ideXlab platform.
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Population Pharmacokinetic Analysis of Panipenem/Betamipron in Patients with Various Degrees of Renal Function
Chemotherapy, 2006Co-Authors: Naoyuki Tajima, Hitoshi Ishizuka, Hideo NaganumaAbstract:Background: Although plasma concentrations of Panipenem were elevated and the risk of adverse events would increase in patients with renal impairment, a precise dosage regimen for p
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population pharmacokinetic analysis of Panipenem betamipron in patients with various degrees of renal function
Chemotherapy, 2006Co-Authors: Naoyuki Tajima, Hitoshi Ishizuka, Hideo NaganumaAbstract:Background: Although plasma concentrations of Panipenem were elevated and the risk of adverse events would increase in patients with renal impairment, a precise dosage regimen for p
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Pharmacokinetics of Panipenem/betamipron in patients with end-stage renal disease
Journal of Infection and Chemotherapy, 2005Co-Authors: Naro Ohashi, Toshihiko Uematsu, Satoru Nagashima, Mitsutaka Kanamaru, Naoyuki Tajima, Akashi Togawa, Akira HishidaAbstract:Panipenem/betamipron (Carbenin), a parenteral carbapenem antibiotic, is used for the treatment of severe and intractable bacterial infections caused by gram-positive and gram-negative bacteria. Because 30% of Panipenem and most of the betamipron are excreted in the urine in an unchanged form, renal function is the important determinant of the dosage regimen of Panipenem/betamipron. In this study, the pharmacokinetics of Panipenem/betamipron were investigated in patients with end-stage renal disease (ESRD) undergoing hemodialysis treatment to establish an appropriate dose regimen. We further attempted to predict the in vivo clearance in patients undergoing hemodialysis based on the in vitro dializability. The pharmacokinetics of Panipenem/betamipron were investigated in eight patients after a 1-h intravenous infusion of Panipenem/betamipron (500 mg/500 mg). The in vitro extraction ratios of Panipenem/betamipron through a high-flux dialyzer were obtained, and compared with those obtained in vivo. The clearances of Panipenem in patients were 9.53 ± 1.26 l/h with hemodialysis, and 2.92 ± 0.238 l/h without hemodialysis. In contrast, those of betamipron were 4.18 ± 0.643 l/h and 0.615 ± 0.511 l/h, respectively. The clearance of Panipenem with hemodialysis were predicted well from in vitro extraction ratios, while that of betamipron was overestimated about 1.4-fold, probably due to high plasma protein binding and the binding difference between patients and healthy subjects. After comparing the pharmacokinetic behavior of Panipenem in patients with ESRD and that of a surrogate marker of efficacy, we recommend that these patients be treated with 500 mg/500 mg of Panipenem/betamipron once daily, which gives a similar clinical result in a patient with normal renal function.
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pharmacokinetics of Panipenem betamipron in patients with end stage renal disease
Journal of Infection and Chemotherapy, 2005Co-Authors: Naro Ohashi, Toshihiko Uematsu, Satoru Nagashima, Mitsutaka Kanamaru, Naoyuki Tajima, Akashi Togawa, Akira HishidaAbstract:Panipenem/betamipron (Carbenin), a parenteral carbapenem antibiotic, is used for the treatment of severe and intractable bacterial infections caused by gram-positive and gram-negative bacteria. Because 30% of Panipenem and most of the betamipron are excreted in the urine in an unchanged form, renal function is the important determinant of the dosage regimen of Panipenem/betamipron. In this study, the pharmacokinetics of Panipenem/betamipron were investigated in patients with end-stage renal disease (ESRD) undergoing hemodialysis treatment to establish an appropriate dose regimen. We further attempted to predict the in vivo clearance in patients undergoing hemodialysis based on the in vitro dializability. The pharmacokinetics of Panipenem/betamipron were investigated in eight patients after a 1-h intravenous infusion of Panipenem/betamipron (500 mg/500 mg). The in vitro extraction ratios of Panipenem/betamipron through a high-flux dialyzer were obtained, and compared with those obtained in vivo. The clearances of Panipenem in patients were 9.53 ± 1.26 l/h with hemodialysis, and 2.92 ± 0.238 l/h without hemodialysis. In contrast, those of betamipron were 4.18 ± 0.643 l/h and 0.615 ± 0.511 l/h, respectively. The clearance of Panipenem with hemodialysis were predicted well from in vitro extraction ratios, while that of betamipron was overestimated about 1.4-fold, probably due to high plasma protein binding and the binding difference between patients and healthy subjects. After comparing the pharmacokinetic behavior of Panipenem in patients with ESRD and that of a surrogate marker of efficacy, we recommend that these patients be treated with 500 mg/500 mg of Panipenem/betamipron once daily, which gives a similar clinical result in a patient with normal renal function.
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Quantitative Evaluation of Effect of Renal Failure on the Pharmacokinetics of Panipenem in Rats
Biological & pharmaceutical bulletin, 2005Co-Authors: Naoyuki Tajima, Masako Soma, Hitoshi Ishizuka, Hideo NaganumaAbstract:The pharmacokinetics of Panipenem in experimental renal failure animal models was investigated in order to identify the appropriate covariates affecting the pharmacokinetic behavior. Panipenem and betamipron were administered intravenously to rats with a variety of renal failures, such as nephritis induced by glycerol, gentamicin, uranium and antiserum against glomerular basement membrane as well as 5/6 subtotal nephrectomy. Panipenem in plasma and urine was determined and pharmacokinetic analysis was performed using a one-compartment open model. The elimination half-life prolonged and total body clearance, renal clearance (CLR) and renal excretion ratio were decreased according to the renal function, i.e. control>glycerol>anti-GBM=gentamicin>nephrectomy=uranium in order. However, distribution volume was consistent in all models. CLR showed strong positive correlation with the glomerular filtration rate in spite of a weak correlation with the reciprocal of blood urea nitrogen. However, no obvious correlation was observed with secretory clearance of N-1-methylnicotinamide. This preliminary information based on animal model might be useful for designing pharmacokinetic studies in special population at early stage of new drug development.
Takaaki Hasegawa - One of the best experts on this subject based on the ideXlab platform.
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Panipenem does not alter the pharmacokinetics of the active metabolite of irinotecan SN-38 and inactive metabolite SN-38 glucuronide (SN-38G) in rats.
Anticancer research, 2011Co-Authors: Ayako Kato, Jun Ueyama, Fumie Abe, Kazuo Hotta, Ikuto Tsukiyama, Taeyuki Oshima, Fumio Kondo, Hiroko Saito, Takaaki HasegawaAbstract:The present study has investigated the effect of Panipenem, a widely used antibiotic, on the pharmacokinetics of an active metabolite of irinotecan (CPT-11), 7-ethyl-10-hydroxy-camptothecin (SN-38) and SN-38 glucuronide (SN-38G) produced by uridine-diphosphate glucuronosyltransferase (UGT) 1A isoform-mediated glucuronidation in rats. Rats received a 1 h infusion with Panipenem at a loading dose of 10 mg/kg and a maintenance dose of 15 mg/min/kg once a day for 5 days. When the effect of pretreatment with Panipenem on glucuronidation activities of substrates for hepatic UGT1A isoforms was investigated using substrates 4-methylumbelliferone (4MU), estradiol and SN-38, the rate of 4MU glucuronide formation was significantly increased, but that of estradiol glucuronide formation was unchanged. However, the rate of SN-38G formation showed a tendency to increase. One hour after the final infusion of Panipenem or saline, SN-38 (2 mg/kg) was administered intravenously in rats with or without bile duct cannulation. Pretreatment with Panipenem had no effect on the plasma concentration-time curves and biliary excretion of SN-38 and SN-38G in rats with and without bile duct cannulation. There were also no significant differences in the relative extent of glucuronidation of SN-38 to SN-38G (AUC(2 h, SN-38G)/AUC(2 h, SN-38)) between Panipenem-treated and untreated rats. These findings suggest that pretreatment with Panipenem does not alter the pharmacokinetics of SN-38 and SN-38G, suggesting the possibility that Panipenem can be used safely for cancer patients undergoing irinotecan chemotherapy.
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Possible mechanism by which the carbapenem antibiotic Panipenem decreases the concentration of valproic acid in plasma in rats.
Antimicrobial agents and chemotherapy, 1998Co-Authors: Saori Kojima, Masayuki Nadai, Kiyoyuki Kitaichi, Li Wang, Toshitaka Nabeshima, Takaaki HasegawaAbstract:There is evidence indicating that the carbapenem antibiotic Panipenem decreases plasma concentrations of valproic acid (VPA) in epileptic patients during VPA therapy. The mechanism for Panipenem-induced changes in the pharmacokinetics of VPA was investigated in rats with and without bile duct cannulation. The effect of Panipenem on the pharmacokinetics of diclofenac, which undergoes extensive enterohepatic recirculation, was also examined. VPA (50 mg/kg of body weight) or diclofenac (10 mg/kg of body weight) was administered intravenously under the steady-state plasma Panipenem concentration of 4 μg/ml, which had been achieved by a constant infusion rate. Panipenem decreased the plasma VPA concentrations in rats without bile duct cannulation but did not change the volume of the initial space and protein binding of VPA. However, Panipenem had no effect on the plasma VPA concentrations and the biliary excretion of VPA in rats with bile duct cannulation. The secondary increase in plasma diclofenac concentration observed in the absence of Panipenem was diminished in the presence of Panipenem. These findings suggest that Panipenem decreases plasma VPA concentrations by suppressing its enterohepatic recirculation, probably due to a Panipenem-induced decrease in the numbers of enteric bacteria.
Naro Ohashi - One of the best experts on this subject based on the ideXlab platform.
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Pharmacokinetics of Panipenem/betamipron in patients with end-stage renal disease
Journal of Infection and Chemotherapy, 2005Co-Authors: Naro Ohashi, Toshihiko Uematsu, Satoru Nagashima, Mitsutaka Kanamaru, Naoyuki Tajima, Akashi Togawa, Akira HishidaAbstract:Panipenem/betamipron (Carbenin), a parenteral carbapenem antibiotic, is used for the treatment of severe and intractable bacterial infections caused by gram-positive and gram-negative bacteria. Because 30% of Panipenem and most of the betamipron are excreted in the urine in an unchanged form, renal function is the important determinant of the dosage regimen of Panipenem/betamipron. In this study, the pharmacokinetics of Panipenem/betamipron were investigated in patients with end-stage renal disease (ESRD) undergoing hemodialysis treatment to establish an appropriate dose regimen. We further attempted to predict the in vivo clearance in patients undergoing hemodialysis based on the in vitro dializability. The pharmacokinetics of Panipenem/betamipron were investigated in eight patients after a 1-h intravenous infusion of Panipenem/betamipron (500 mg/500 mg). The in vitro extraction ratios of Panipenem/betamipron through a high-flux dialyzer were obtained, and compared with those obtained in vivo. The clearances of Panipenem in patients were 9.53 ± 1.26 l/h with hemodialysis, and 2.92 ± 0.238 l/h without hemodialysis. In contrast, those of betamipron were 4.18 ± 0.643 l/h and 0.615 ± 0.511 l/h, respectively. The clearance of Panipenem with hemodialysis were predicted well from in vitro extraction ratios, while that of betamipron was overestimated about 1.4-fold, probably due to high plasma protein binding and the binding difference between patients and healthy subjects. After comparing the pharmacokinetic behavior of Panipenem in patients with ESRD and that of a surrogate marker of efficacy, we recommend that these patients be treated with 500 mg/500 mg of Panipenem/betamipron once daily, which gives a similar clinical result in a patient with normal renal function.
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pharmacokinetics of Panipenem betamipron in patients with end stage renal disease
Journal of Infection and Chemotherapy, 2005Co-Authors: Naro Ohashi, Toshihiko Uematsu, Satoru Nagashima, Mitsutaka Kanamaru, Naoyuki Tajima, Akashi Togawa, Akira HishidaAbstract:Panipenem/betamipron (Carbenin), a parenteral carbapenem antibiotic, is used for the treatment of severe and intractable bacterial infections caused by gram-positive and gram-negative bacteria. Because 30% of Panipenem and most of the betamipron are excreted in the urine in an unchanged form, renal function is the important determinant of the dosage regimen of Panipenem/betamipron. In this study, the pharmacokinetics of Panipenem/betamipron were investigated in patients with end-stage renal disease (ESRD) undergoing hemodialysis treatment to establish an appropriate dose regimen. We further attempted to predict the in vivo clearance in patients undergoing hemodialysis based on the in vitro dializability. The pharmacokinetics of Panipenem/betamipron were investigated in eight patients after a 1-h intravenous infusion of Panipenem/betamipron (500 mg/500 mg). The in vitro extraction ratios of Panipenem/betamipron through a high-flux dialyzer were obtained, and compared with those obtained in vivo. The clearances of Panipenem in patients were 9.53 ± 1.26 l/h with hemodialysis, and 2.92 ± 0.238 l/h without hemodialysis. In contrast, those of betamipron were 4.18 ± 0.643 l/h and 0.615 ± 0.511 l/h, respectively. The clearance of Panipenem with hemodialysis were predicted well from in vitro extraction ratios, while that of betamipron was overestimated about 1.4-fold, probably due to high plasma protein binding and the binding difference between patients and healthy subjects. After comparing the pharmacokinetic behavior of Panipenem in patients with ESRD and that of a surrogate marker of efficacy, we recommend that these patients be treated with 500 mg/500 mg of Panipenem/betamipron once daily, which gives a similar clinical result in a patient with normal renal function.
Chul Won Jung - One of the best experts on this subject based on the ideXlab platform.
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Panipenem Versus Cefepime as Empirical Monotherapy in Adult Cancer Patients with Febrile Neutropenia: A Prospective Randomized Trial
Japanese journal of clinical oncology, 2008Co-Authors: Ki Tae Kwon, Hae Suk Cheong, Ji-young Rhee, Seong Yeol Ryu, Sang Taek Heo, Chi Sook Moon, Ki-hyun Kim, Chul Won JungAbstract:Objective: To compare the efficacy and safety of Panipenem/betamipron with cefepime as empirical monotherapy for adult cancer patients with febrile neutropenia, a randomized, open-label, comparative trial was performed. Methods: All enrolled patients were randomly assigned to receive either Panipenem or cefepime. All febrile episodes were classified as microbiologically defined infection (MDI), clinically defined infection (CDI) or unexplained fever (UF). Clinical responses to antibiotic therapy were defined as success, initial response but regimen modified or failure. Results: A total of 116 patients were enrolled: 55 patients in the Panipenem group and 61 patients in the cefepime group. Demographic and clinical characteristics were similar in the two groups (P . 0.05). In the final evaluation, the success rate for the Panipenem group (89.1%) was similar to that of the cefepime group (91.8%) (non-inferiority, P ¼ 0.002, 95% confidence interval: 213.48%, 10.35%). Of the 18 bacterial isolates, nine (50%) were grampositive and nine (50%) were gram-negative. The prevalence of adverse events in the Panipenem group (23.6%) were similar to those in the cefepime group (23.0%) (P ¼ 0.93). All of the adverse events were well tolerated and transient. Conclusions: Although larger studies are necessary, Panipenem appeared to be as effective and safe as cefepime for empirical monotherapy in the treatment of adult cancer patients with febrile neutropenia.
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Original Article Panipenem Versus Cefepime as Empirical Monotherapy in Adult Cancer Patients with Febrile Neutropenia: A Prospective Randomized Trial
2007Co-Authors: Ki Tae Kwon, Hae Suk Cheong, Ji-young Rhee, Seong Yeol Ryu, Sang Taek Heo, Chi Sook Moon, Ki-hyun Kim, Chul Won JungAbstract:Objective: To compare the efficacy and safety of Panipenem/betamipron with cefepime as empirical monotherapy for adult cancer patients with febrile neutropenia, a randomized, open-label, comparative trial was performed. Methods: All enrolled patients were randomly assigned to receive either Panipenem or cefe-pime. All febrile episodes were classified as microbiologically defined infection (MDI), clini-cally defined infection (CDI) or unexplained fever (UF). Clinical responses to antibiotic therapy were defined as success, initial response but regimen modified or failure. Results: A total of 116 patients were enrolled: 55 patients in the Panipenem group and 61 patients in the cefepime group. Demographic and clinical characteristics were similar in the two groups (P. 0.05). In the final evaluation, the success rate for the Panipenem group (89.1%) was similar to that of the cefepime group (91.8%) (non-inferiority, P 0.002, 95% confidence interval: 213.48%, 10.35%). Of the 18 bacterial isolates, nine (50%) were gram-positive and nine (50%) were gram-negative. The prevalence of adverse events in the panipe
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Panipenem Versus Cefepime as Empirical Monotherapy in Adult Cancer Patients with Febrile Neutropenia: A Prospective Randomized Trial
2007Co-Authors: Ki Tae Kwon, Hae Suk Cheong, Ji-young Rhee, Seong Yeol Ryu, Sang Taek Heo, Chi Sook Moon, Ki-hyun Kim, Chul Won JungAbstract:Objective: To compare the efficacy and safety of Panipenem/betamipron with cefepime as empirical monotherapy for adult cancer patients with febrile neutropenia, a randomized, open-label, comparative trial was performed. Methods: All enrolled patients were randomly assigned to receive either Panipenem or cefe-pime. All febrile episodes were classified as microbiologically defined infection (MDI), clini-cally defined infection (CDI) or unexplained fever (UF). Clinical responses to antibiotic therapy were defined as success, initial response but regimen modified or failure. Results: A total of 116 patients were enrolled: 55 patients in the Panipenem group and 61 patients in the cefepime group. Demographic and clinical characteristics were similar in the two groups (P. 0.05). In the final evaluation, the success rate for the Panipenem group (89.1%) was similar to that of the cefepime group (91.8%) (non-inferiority, P 0.002, 95% confidence interval: 213.48%, 10.35%). Of the 18 bacterial isolates, nine (50%) were gram-positive and nine (50%) were gram-negative. The prevalence of adverse events in the panipe
