摘要:

Abstract(i)The urinary elimination of methoxyphenamine (MPA) and its metabolites in underivatized samples was examined after single and multiple oral administration to pregnant and non‐pregnant mice by GLC and GLC—MS.(ii)The major metaboliteO‐desmethylmethoxyphenamine (ODMP), along with lesser amounts ofN‐desmethylmethoxyphenamine (NDMP) and 2‐hydroxyamphetamine (2OH), were the only metabolites detected in urine extracts of pregnant and non‐pregnant mice. 5‐Hydroxymethoxyphenamine (5HMP) was not detected. Enzyme hydrolysis did not increase the recovery of either substrate or metabolites in either the pregnant or non‐pregnant animals. The results show that MPA metabolism in the Swiss—Webster mouse is distinctly different from that seen in man and other laboratory animals.(iii)The mean MPA:ODMP ratio in day‐6 urine from pregnant mice after a single dose was 0.31 ± 0.04. The NDMP:ODMP ratios were less than 0.10 in all samples. Non‐pregnant mice urine had equivalent amounts of MPA, NDMP, ODMP, and 2OH after multiple dosing.(iv)While multiple dosing and pregnancy did not alter either the urinary recovery or profile of the metabolites detected, there was a linear decrease in the MPA:ODMP ratio during gestation.(v)MPA was extensively metabolized to ODMP in the male mice, and the MPA:ODMP ratio of 0.41 was slightly higher than that observed in the pregnant an

ISSN:0142-2782    

DOI:10.1002/bdd.2510160102

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractThe pharmacokinetic behavior of glycyrrhizin in four patients with acute hepatitis (hepatitis group) and six patients with liver cirrhosis (cirrhosis group) receiving chronically an IV administration of a 120 mg dose once a day or once every other day of glycyrrhizin was investigated. The plasma concentration of glycyrrhizin declined monoexponentially in both groups. The elimination half‐life (t1/2) for glycyrrhizin in the hepatitis and cirrhosis groups varied significantly in the range of 2.7–7.6 h and 6.2–40.1 h, and the total body clearance (CLtot) in the range of 2.8–23.2 mL h−1kg−1and 1.4–12.9 mL h−1kg−1, respectively. Thet1/2for glycyrrhizin in the hepatitis and the cirrhosis groups was about twice and eight times that in normal subjects, respectively, as reported previously, and CLtotvalues were about 0.7 and 0.23 times that in normal subjects, respectively. There was significant correlation between the CLtotand hepatic function (asparatate aminotransferase and alanine aminotransferase in serum) in both patient groups. With improvement of the liver function, the CLtotfor glycyrrhizin increased from 2.8 ml h−1kg−1to 11.4 mL h−1kg−1, and thet1/2shortened from 7.6 h to 3.4 h. These findings indicated that the variation of pharmacokinetic behaviour of glycyrrhizin in both groups was closely related to the ext

ISSN:0142-2782    

DOI:10.1002/bdd.2510160103

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractThe dialyser clearance of a drug is the sum of two components: one diffusive, arising from the concentration gradient across the membrane, and the other convective, arising from the ultrafiltration of plasma water, produced by the increases in hydraulic pressure that the membrane undergoes.To demonstrate the importance of these clearnces during haemodialysis, this study analyses the influence of a drug's molecular weight on them.To this end, an experimental study of dialysisin vitrowas carried out to determine the clearances, in aqueous solution, of five drugs of increasing molecular weights (theophylline, quinidine, tobramycin, digoxin, and vancomycin), using two series of dialysers with the same type of membrane (Cuprophan®), differing in effective surface area and ultrafiltration coefficient.From the data obtained in this study, the importance of quantifying convective clearance during haemodialysis becomes apparent since if it is not taken into account errors of up to 20% and more may be made. This is particularly so if the drug is of high molecular weight and if a high filtration rate is being used

ISSN:0142-2782    

DOI:10.1002/bdd.2510160104

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractSix numerical integration algorithms based on linear and log trapezoidal methods as well as four cubic‐spline methods were proposed for estimation of area under the curve (AUC). These six different algorithms were implemented using IMSL/IDLTMcommand language and evaluated using data simulated under five different dosing conditions and two different sampling conditions. Comparisons between AUC estimations using these six different algorithms and the theoretical results were made in terms of both overall AUC values and the superimposability of the concentration‐time profiles. In well designed studies with ample data points, the algorithm based on IMSL/IDLTMfunction CSSHAPE with concavity preservation gave the best performance. In contrast, when the frequency of blood collection was limited, the algorithm based on the log trapezoidal rule proved to be stable with reasonable accuracy, and is recommended as the practical method for numerical interpolation and integration in pharmacokinetic studies. Algorithms based on the combination of the log trapezoidal rule and cubic‐spline methods using IMSL/IDLTMfunction CSSHAPE can be developed to enhance overall perfor

ISSN:0142-2782    

DOI:10.1002/bdd.2510160105

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractWe estimated the free fraction (fu) of cyclosporine (CyA) in the plasma from concentrations of CyA in urine (Cu) and plasma (Cp), urine flow rate (UF), and glomerular filtration rate in rabbits and in heart transplant patients. Following intravenous administration of CyA (5–30 mg kg−1) in ten NZW rabbits and oral administration of CyA (4.8–12.1 mg kg−1) in nine heart transplant patients, CyA concentrations in urine and plasma were measured by HPLC. The ratios ofCutoCpand UF data were fitted to a physiological model of renal clearance using NONMEM. The free fraction of cyclosporine in the rabbits and the heart transplant patients was 0.0122 and 0.14, respectively. Because of the relatively low permeability of CyA across the tubular epithelium, no apparent equilibrium betweenCuandCpat any urine flow rate was reached and, therefore, theCutoCpratio will not be equ

ISSN:0142-2782    

DOI:10.1002/bdd.2510160106

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

ISSN:0142-2782    

DOI:10.1002/bdd.2510160107

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

ISSN:0142-2782    

DOI:10.1002/bdd.2510160108

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY