To assess the influence of cyclosporin A (CsA) and tacrolimus (FK506) on mycophenolic acid (MPA) and correlation analysis of the pharmacokinetic parameters and patient characteristics, clinical outcome in Chinese kidn...To assess the influence of cyclosporin A (CsA) and tacrolimus (FK506) on mycophenolic acid (MPA) and correlation analysis of the pharmacokinetic parameters and patient characteristics, clinical outcome in Chinese kidney transplant recipients, the pharmacokinetics of 1000 mg mycophenolate mofetil (MMF) twice daily was measured by high-performance liquid chro- matography (HPLC). PKS (Pharmaceutical Kinetics Software) 1.0.2 software package was used for the calculation of pharma- cokinetic parameters. The mean Cmax, tmax, and AUC(0?12)were (21.88±10.52) μg/ml, (1.20±0.95) h, and (52.546±13.215) μg·h/ml, respectively. The level of AUC(0?12) in the FK506 group was significantly higher than that in the CsA group. MPA appeared not to be affected by renal function. MPA AUC(0?12) showed statistically significant difference according to the patient’s gender.展开更多
Background: Mycophenolate Mofetil (MMF) is widely used in organ transplant patients to avoid calcineurine inhibittor-associated side effects. Therapeutic monitoring of MMF is up to now perform by using trough level me...Background: Mycophenolate Mofetil (MMF) is widely used in organ transplant patients to avoid calcineurine inhibittor-associated side effects. Therapeutic monitoring of MMF is up to now perform by using trough level measurements (measurements before drug administration). The present study was designed to characterize potential differences in MMF absorption kinetics between patients with allogenic kidney transplantation [kidney Tx] and simultaneous pancreas kidney transplantation [PK Tx], which might for example occur due to diabetic gastrointestinal atony. Methods: A total of 64 pharmacokinetic profiles were prospectively studied in 44 adult kidney Tx and 20 PK Tx patients. To calculate AUC by the trapezoidal rule, mycophenolic acid (MPA) levels were measured in EDTA-plasma by an EMIT assay at 0, 0.5, 1, 2, 3, 4 6, and 12h after oral MMF administration between postoperative day 14 to 28 instable patients. Results: Substantial differences between kidney Tx and PK Tx patients were evident concerning: donor age, recipient age, number of mismatches, and kidney function (serum creatinine). Despite these dissimilarities pharmacokinetic absorption profiles did not significantly differ between patient groups as measured by AUC, C2, maximum MPA concentration (Cmax), and time until maximum absorption (Tmax). Astonishingly, concomitant cyclosporine and tacrolimus medication did not influence adsorption profiles. Only MPA concentrations 6h post administration correlated closely with AUC in both patient groups, whereas trough levels failed to be predictive for AUC. Conclusions: In our study population, MMF absorption kinetics did not differ between kidney and PK Tx patients and did not seem influenced by concomitant immunosuppressive medication. Therefore, MPA measurements during the absorption phase could be useful to better estimate AUC in patients with kidney Tx and PK Tx.展开更多
The aim of the research was to investigate the pharmacokinetics(PK) of enteric-coated mycophenolate sodium(EC-MPS) by quantification of the active metabolite of mycophenolic acid(MPA)after multiple escalating oral dos...The aim of the research was to investigate the pharmacokinetics(PK) of enteric-coated mycophenolate sodium(EC-MPS) by quantification of the active metabolite of mycophenolic acid(MPA)after multiple escalating oral doses in Han kidney transplant recipients. A total of 28 Han postoperative kidney transplant recipients were given a multiple-dose of 540, 720 or 900 mg of EC-MPS two times a day in combination with tacrolimus for 6 days. Blood specimens were collected at each time point from0 to 12 h after EC-MPS administration. MPA plasma concentrations were measured by UPLC–UV. The relationship between the EC-MPS dose and its PK parameters was assessed. In the range from 540 to900 mg, C_(max) and AUC_(0–12h) did not increase with dose escalation. The AUC_(0–12h), C_(max), C_0 and T_(max) for the 540 720 and 900 mg doses were not significantly different, respectively(P 40.05). AUC_0–12 h and C_(max) were increased less than proportionally with increasing EC-MPS dose levels. Inter-individual variability in AUC_(0–12h), C_(max) and C_0 were considerable. Nonlinear PK relationships were found from the doses of 540–900 mg of EC-MPS.展开更多
目的:观察肾移植术后不同时间麦考酚酸暴露量的变化,为肾移植术后麦考酚吗乙酯剂量的调整提供理论依据。方法:16例首次肾移植患者,均于肾移植术后24小时内给予麦考酚吗乙酯(mycophenolate mofetil,MMF)1.5g/d治疗,长期应用。于术后第7...目的:观察肾移植术后不同时间麦考酚酸暴露量的变化,为肾移植术后麦考酚吗乙酯剂量的调整提供理论依据。方法:16例首次肾移植患者,均于肾移植术后24小时内给予麦考酚吗乙酯(mycophenolate mofetil,MMF)1.5g/d治疗,长期应用。于术后第7日、第28日、第90日测定其服药前、服药后半小时及服药后2小时的麦考酚酸的血药浓度,采用Shaw简易公式计算对应的麦考酚酸血药浓度-时间曲线下面积(the area under the drug concentration in the plasma versurs time curve,AUC)并比较其差异。结果:术后第7日、第28日、第90日的麦考酚酸AUC分别为(32±9)(mg/L).h、(41±10)(mg/L).h和(47±13)(mg/L).h,比较差异均有统计学意义(均为P<0.05)。结论:在术后3个月内连续服用同等剂量(1.5g/d)MMF的情况下,麦考酚酸AUC逐渐升高,在术后第90日达到(47±13)(mg/L).h,已超过能有效预防急性排斥反应的AUC。提示应在用药的90日内监测麦考酚酸AUC,并及时减少用量,以免发生严重的不良反应。展开更多
基金Project (No. 20040462) supported by the Foundation of EducationBureau of Zhejiang Province, China
文摘To assess the influence of cyclosporin A (CsA) and tacrolimus (FK506) on mycophenolic acid (MPA) and correlation analysis of the pharmacokinetic parameters and patient characteristics, clinical outcome in Chinese kidney transplant recipients, the pharmacokinetics of 1000 mg mycophenolate mofetil (MMF) twice daily was measured by high-performance liquid chro- matography (HPLC). PKS (Pharmaceutical Kinetics Software) 1.0.2 software package was used for the calculation of pharma- cokinetic parameters. The mean Cmax, tmax, and AUC(0?12)were (21.88±10.52) μg/ml, (1.20±0.95) h, and (52.546±13.215) μg·h/ml, respectively. The level of AUC(0?12) in the FK506 group was significantly higher than that in the CsA group. MPA appeared not to be affected by renal function. MPA AUC(0?12) showed statistically significant difference according to the patient’s gender.
文摘Background: Mycophenolate Mofetil (MMF) is widely used in organ transplant patients to avoid calcineurine inhibittor-associated side effects. Therapeutic monitoring of MMF is up to now perform by using trough level measurements (measurements before drug administration). The present study was designed to characterize potential differences in MMF absorption kinetics between patients with allogenic kidney transplantation [kidney Tx] and simultaneous pancreas kidney transplantation [PK Tx], which might for example occur due to diabetic gastrointestinal atony. Methods: A total of 64 pharmacokinetic profiles were prospectively studied in 44 adult kidney Tx and 20 PK Tx patients. To calculate AUC by the trapezoidal rule, mycophenolic acid (MPA) levels were measured in EDTA-plasma by an EMIT assay at 0, 0.5, 1, 2, 3, 4 6, and 12h after oral MMF administration between postoperative day 14 to 28 instable patients. Results: Substantial differences between kidney Tx and PK Tx patients were evident concerning: donor age, recipient age, number of mismatches, and kidney function (serum creatinine). Despite these dissimilarities pharmacokinetic absorption profiles did not significantly differ between patient groups as measured by AUC, C2, maximum MPA concentration (Cmax), and time until maximum absorption (Tmax). Astonishingly, concomitant cyclosporine and tacrolimus medication did not influence adsorption profiles. Only MPA concentrations 6h post administration correlated closely with AUC in both patient groups, whereas trough levels failed to be predictive for AUC. Conclusions: In our study population, MMF absorption kinetics did not differ between kidney and PK Tx patients and did not seem influenced by concomitant immunosuppressive medication. Therefore, MPA measurements during the absorption phase could be useful to better estimate AUC in patients with kidney Tx and PK Tx.
基金supported by the youth fund of The First Affiliated Hospital of Zhengzhou University
文摘The aim of the research was to investigate the pharmacokinetics(PK) of enteric-coated mycophenolate sodium(EC-MPS) by quantification of the active metabolite of mycophenolic acid(MPA)after multiple escalating oral doses in Han kidney transplant recipients. A total of 28 Han postoperative kidney transplant recipients were given a multiple-dose of 540, 720 or 900 mg of EC-MPS two times a day in combination with tacrolimus for 6 days. Blood specimens were collected at each time point from0 to 12 h after EC-MPS administration. MPA plasma concentrations were measured by UPLC–UV. The relationship between the EC-MPS dose and its PK parameters was assessed. In the range from 540 to900 mg, C_(max) and AUC_(0–12h) did not increase with dose escalation. The AUC_(0–12h), C_(max), C_0 and T_(max) for the 540 720 and 900 mg doses were not significantly different, respectively(P 40.05). AUC_0–12 h and C_(max) were increased less than proportionally with increasing EC-MPS dose levels. Inter-individual variability in AUC_(0–12h), C_(max) and C_0 were considerable. Nonlinear PK relationships were found from the doses of 540–900 mg of EC-MPS.
文摘目的:观察肾移植术后不同时间麦考酚酸暴露量的变化,为肾移植术后麦考酚吗乙酯剂量的调整提供理论依据。方法:16例首次肾移植患者,均于肾移植术后24小时内给予麦考酚吗乙酯(mycophenolate mofetil,MMF)1.5g/d治疗,长期应用。于术后第7日、第28日、第90日测定其服药前、服药后半小时及服药后2小时的麦考酚酸的血药浓度,采用Shaw简易公式计算对应的麦考酚酸血药浓度-时间曲线下面积(the area under the drug concentration in the plasma versurs time curve,AUC)并比较其差异。结果:术后第7日、第28日、第90日的麦考酚酸AUC分别为(32±9)(mg/L).h、(41±10)(mg/L).h和(47±13)(mg/L).h,比较差异均有统计学意义(均为P<0.05)。结论:在术后3个月内连续服用同等剂量(1.5g/d)MMF的情况下,麦考酚酸AUC逐渐升高,在术后第90日达到(47±13)(mg/L).h,已超过能有效预防急性排斥反应的AUC。提示应在用药的90日内监测麦考酚酸AUC,并及时减少用量,以免发生严重的不良反应。
