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1.
Clin Exp Nephrol ; 13(2): 123-129, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19057979

ABSTRACT

BACKGROUND/AIMS: The present study evaluated the clinical efficacy and pharmacokinetics of microemulsion cyclosporine A (ME-CyA) with modification from postprandial to preprandial administration in adult patients with refractory nephrotic syndrome. METHODS: We investigated 19 patients with refractory nephrotic syndrome who had been switched from the postprandial administration of ME-CyA to preprandial administration. The pharmacokinetics of ME-CyA were also evaluated before and 6 months after switching from postprandial to preprandial administration by serial measurement of the blood CyA concentration in 10 patients. RESULTS: This study showed that 16 of 19 patients (84%) displayed an improvement in their clinical condition or continued to maintain remission after switching from post- to preprandial administration. In particular among 14 patients with minimal change nephrotic syndrome (MCNS) in this study, 13 patients maintained or achieved remission under preprandial ME-CyA administration. Only three of 10 patients with postprandial administration showed a peak concentration> 500 ng/ml within 1-2 h after administration, while with preprandial administration, nine of 10 patients showed this good absorption profiles. This effectiveness of preprandial administration seems to be dependent on the improved pharmacokinetics with the increase of area under the curve from 0-4 h (AUC(0-4)) and peak concentration. There were no statistical differences in the mean daily doses of ME-CyA between both administration periods. No ME-CyA-induced nephrotoxicity or other harmful events were encountered throughout the study. CONCLUSION: The preprandial administration of ME-CyA results in a good pharmacokinetic profile and is useful for management of refractory nephrotic syndrome in adults, particularly in patients with MCNS.


Subject(s)
Cyclosporine/administration & dosage , Cyclosporine/pharmacokinetics , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/pharmacokinetics , Intestinal Absorption , Nephrosis, Lipoid/drug therapy , Administration, Oral , Adolescent , Adult , Aged , Cyclosporine/blood , Emulsions , Humans , Immunosuppressive Agents/blood , Middle Aged , Postprandial Period , Young Adult
2.
J Clin Pharmacol ; 46(1): 59-68, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16397285

ABSTRACT

Population pharmacokinetics (PK) of a sodium channel-blocking antiarrhythmic, pilsicainide, was studied using the nonlinear mixed-effects modeling technique in 91 patients with cardiac arrhythmias (80 suspected Brugada syndrome [BrS] and 11 with atrial fibrillation) who received an intravenous infusion of 10 mg of the drug. Population pharmacodynamic (PD) analysis was also performed using an effect compartment model. PD responses were assessed by changes in electrocardiogram (ECG) pattern (BrS-like elevation of ST-segment) and conduction parameters. The final PK model showed that gender (values were 50% lower in women than in men) and creatinine clearance were significant (P < .01) covariates of weight-normalized systemic clearance of pilsicainide. Patients who showed a BrS-like ECG pattern after the drug administration also showed a significantly (P < .01) greater prolongation in His-Purkinje conduction compared to the remaining patients. In conclusion, female gender, renal dysfunction, and the drug-induced BrS-like ECG morphology may be associated with augmented ECG responses to pilsicainide.


Subject(s)
Anti-Arrhythmia Agents/pharmacokinetics , Arrhythmias, Cardiac/metabolism , Lidocaine/analogs & derivatives , Sodium Channel Blockers/pharmacokinetics , Adult , Aged , Anti-Arrhythmia Agents/therapeutic use , Arrhythmias, Cardiac/diagnosis , Arrhythmias, Cardiac/drug therapy , Atrial Fibrillation/drug therapy , Atrial Fibrillation/metabolism , Bundle-Branch Block/diagnosis , Bundle-Branch Block/metabolism , Creatinine/urine , Electrocardiography/drug effects , Female , Heart Conduction System/drug effects , Humans , Kidney/metabolism , Lidocaine/pharmacokinetics , Lidocaine/therapeutic use , Male , Middle Aged , Models, Biological , Sex Factors , Sodium Channel Blockers/therapeutic use
3.
Yakugaku Zasshi ; 125(3): 307-14, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15738630

ABSTRACT

Diazepam is commonly used as premedicant for endoscopic procedures. Wide interindividual differences have been observed in the residual cognitive effects of the drug after gastrointestinal endoscopy. Our aim was to clarify the major factors, including pharmacokinetic factors, contributing to this wide variation in residual cognitive effect after gastrointestinal endoscopy in the study. Sixty-one outpatients undergoing gastrointestinal endoscopy participated in the study. Cognitive effects were evaluated in the diazepam group (n=52) by the digit symbol substitution test (DSST) twice before and 30 min after an intravenous administration of 5 mg diazepam; in the intervening time gastrointestinal endoscopy was performed. Plasma concentrations of diazepam were determined by HPLC. The control group (n=9) was tested by DSST in the same manner. The cognitive effects according to the change in DSST score was significantly decline in the diazepam group compared with the control group (by 0.2 versus -4.6; P=0.014). This prospective study confirmed that cognition was significantly impaired after gastrointestinal endoscopy by premedication to subjects with 5 mg diazepam. There were very wide variations in change in DSST score. However we could not identify the independent variables that best predicted DSST score difference in a multiple regression analysis for age, plasma albumin level, and plasma diazepam concentration 30 min after intravenous administration. We should pay attention to patients' individual states in cognitive performance following gastrointestinal endoscopy after single-dose diazepam.


Subject(s)
Anti-Anxiety Agents/adverse effects , Cognition Disorders/chemically induced , Diazepam/adverse effects , Endoscopy, Gastrointestinal , Outpatients , Adult , Aged , Alleles , Anti-Anxiety Agents/administration & dosage , Anti-Anxiety Agents/blood , Aryl Hydrocarbon Hydroxylases/genetics , Cognition Disorders/diagnosis , Cytochrome P-450 CYP2C19 , Diazepam/administration & dosage , Diazepam/blood , Female , Genotype , Humans , Infusions, Intravenous , Male , Middle Aged , Mixed Function Oxygenases/genetics , Preanesthetic Medication , Prospective Studies
4.
Pharmacotherapy ; 25(1): 52-8, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15767220

ABSTRACT

STUDY OBJECTIVE: To compare the absorption profile of cyclosporine after preprandial administration with that after postprandial administration, and to determine which administration time resulted in a more stable absorption profile and the timing of the drug concentration that was the most reliable marker for monitoring drug absorption. DESIGN: Prospective analysis. SETTING: University teaching hospital in Japan. PATIENTS: Sixteen patients with refractory nephrotic syndrome. INTERVENTION: Thirteen patients received cyclosporine after breakfast (postprandial group) and eight received the drug 30 minutes before breakfast (preprandial group). MEASUREMENTS AND MAIN RESULTS: Blood cyclosporine concentration was measured 5 times serially: before administration (C 0 ) and at 1-hour intervals until 4 hours after administration of cyclosporine (C 1 -C 4 ). Also, area under the concentration-time curve from 0-4 hours (AUC 0-4 ) was calculated. Of the 13 patients in the postprandial group, six (46%) showed fair absorption and exhibited a peak concentration at C 1 or C 2 (high-absorption pattern); seven (54%) showed poor absorption and did not reach the peak concentration within the 4-hour period (low-absorption pattern). Five of the seven patients with the low-absorption pattern were switched from postprandial to preprandial administration. All patients in the preprandial administration group showed a high-absorption pattern and reached the peak cyclosporine concentration at C 1 . The C 2 value showed the best correlation with AUC 0-4 in both groups, and the C 0 parameter did not correlate with AUC 0-4 in either group. CONCLUSION: Preprandial administration provided a more stable absorption profile of cyclosporine compared with postprandial administration. From the correlation with AUC 0-4 , we concluded that C 2 , and not C 0 , is a reliable marker for monitoring cyclosporine exposure.


Subject(s)
Cyclosporine/pharmacokinetics , Fasting , Nephrotic Syndrome/diagnosis , Nephrotic Syndrome/drug therapy , Postprandial Period , Severity of Illness Index , Absorption , Area Under Curve , Cyclosporine/administration & dosage , Cyclosporine/metabolism , Drug Administration Schedule , Hospitals, University , Humans , Middle Aged , Nephrotic Syndrome/physiopathology , Prospective Studies , Time Factors
5.
Jpn J Antibiot ; 55(1): 77-88, 2002 Feb.
Article in Japanese | MEDLINE | ID: mdl-11977923

ABSTRACT

Complication by secondary infection is observed in not only bacterial pleurisy but also other pleurisy, and the appropriate administration of antibacterial agents is necessary. It is very important to secure a smooth penetration of systemically administered antibacterial agents to pleural effusion in infection therapy. In this study, we investigated the pharmacokinetics of a carbapenem antibiotic, meropenem (MEPM), in blood and pleural effusion in patients with an accumulation of pleural effusion caused by pleurisy, who underwent placement of an indwelling thoracic drain and received intravenous drip administration of MEPM for pneumonia or other respiratory tract infection. The blood pharmacokinetic parameters of MEPM after an intravenous drip administration of 0.5 g MEPM in six patients were: area under the blood concentration-time curve (AUCx), 37.9 +/- 6.2 (hr.mg/L); volume of distribution (Vd), 27.3 +/- 4.4 (L); total clearance (CLtotal), 13.4 +/- 1.8 (L/hr); elimination half life (t1/2), 0.50 +/- 0.08 (hr-1); and elimination rate constant (kel), 1.42 +/- 0.22 (hr). The pharmacokinetic parameters in pleural effusion were: AUCx, 35.7 +/- 7.1 (hr.mg/L); mean retention time (MRT), 5.00 +/- 3.25 (hr); variance of retention time (VRT), 29.9 +/- 44.6 (hr2); kel, 0.34 +/- 0.27 (hr-1); and t1/2, 3.14 +/- 2.36 (hr). The penetration rate calculated from the ratio of pleural concentration to blood concentration in each patient was 46.5 +/- 26.1%, showing good penetration comparable or superior to those of other antibacterial agents previously reported. From these results, it was suggested that MEPM was rapidly penetrated to the pleural effusion and was retained for a more prolonged time in the pleural effusion than in the blood of patients with accumulated pleural effusion, and it suggested the usefulness of MEPM in antibacterial therapy for patients with pleurisy causing accumulation of pleural effusion.


Subject(s)
Pleural Effusion/metabolism , Pleurisy/metabolism , Thienamycins/pharmacokinetics , Aged , Female , Humans , Male , Meropenem , Middle Aged , Thienamycins/administration & dosage
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