ISSN:0163-4356    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

A method for rapid assessment of hepatic function in cirrhotics based on the formation of the lidocaine metabolite, monoethylglycinexylidide (MEGX), was evaluated. The formation kinetics and urinary excretion patterns of MEGX clearly distinguished cirrhotics (n= 12) from healthy volunteers (n= 16). In a prospective study, we compared the prognostic value of the MEGX test with that of traditional parameters in transplant candidates. Patients who underwent transplantation during follow-up were excluded. The study included 58 adult patients with biopsy-proven posthepatitic or biliary cirrhosis. During the follow-up period of 120 days, 10 of 58 patients died of their liver disease. At the time of inclusion, we recorded MEGX formation, indocyanine green (ICG) half-life, caffeine clearance, and the Child-Pugh score. These variables were subjected as covariates to a survival analysis (Cox proportional hazards regression model). The results of the MEGX and the ICG test were significantly related to the 120-day survival. In the stepwise analysis, none of the parameters evaluated contributed to a further significant improvement of our predictive ability when added to the values of ICG (improvement:p< 0.0005) and MEGX (improvement:p< 0.0005). These findings suggest that the ICG and MEGX tests were the best short-term prognostic indicators. The easy handling favors the MEGX test over the ICG test as a tool for assessment of hepatic function and short-term prognosis in transplant candidates with cirrhosis.

ISSN:0163-4356    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Plasma levels and cumulative urine excretion of 6-mercaptopurine (6-MP) were measured using a specific and sensitive high-performance liquid chromatographic assay in seven children with acute lymphoblastic leukemia (ALL) as well as in one healthy volunteer. The dose of 6-MP varied in the range of 25–75 mg/m2of body surface area and was administered with a standard breakfast. A 4− to 11-fold variation between individuals was found in the pharmacokinetic parameters: peak concentration, time to reach peak, area under the plasma concentration-time curve (AUC), and fraction of dose excreted in the urine. Three repeated determinations in one individual revealed that AUC also varied more than sixfold following an overnight fast. In three individuals, the reducing agents glutathione (10 mg/kg) and ascorbic acid (15 mg/kg) were coadministered with 6-MP to evaluate their possible role in the protection of 6-MP from oxidation and degradation in the intestinal lumen. No consistent effect was observed, however, on the AUCs of either of these agents. A clear relationship was found between AUCs and the 24-h urinary excretion of unchanged drug (r= 0.9381), indicating that determinations of 6-MP in the urine may replace the painful procedure of repeated blood sampling. Further studies are necessary to determine the factors contributing to the unpredictable plasma levels following oral doses of 6-MP and to determine the value of pharmacokinetic monitoring in ALL patients.

ISSN:0163-4356    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Free and total carbamazepine (CBZ) and carbamazepine-epoxide (CBZ-EP) plasma levels were obtained on 113 patients with epilepsy (18–61 years old) controlled on either monotherapy or coadministration with either phenobarbital (PB), phenytoin (PHT), valproic acid (VPA), or all three. A subset of patients were administered tetradeuterium labeled CBZ to evaluate the effects of autoinduction and coadministration of VPA on the kinetics of CBZ and its metabolite CBZ-EP. Polytherapy had variable effect on free and total CBZ plasma levels compared to monotherapy. Coadministered PHT (co-PHT), or all three anticonvulsants together (PHT, PB, and VPA: co-AEDs) decreased free and total CBZ plasma levels. No change was noted for coadministered VPA (co-VPA). Compared to monotherapy the free and total CBZ-EP levels increased with co-VPA, less with coadministered PB (co-PB), and no change with co-PHT or co-AEDs. Protein binding of CBZ and CBZ-EP was not affected by any antiepileptic drugs studied. The free and total CBZ-EP/CBZ ratio was tripled with co-VPA or co-AED's, and doubled with co-PHT or co-PB. Isotope labeling did not demonstrate any differences in half-life (t1/2), plasma clearance (Cl), or volume of distribution (Vd). Compared to naive controls, monotherapy and co-VPA decreased CBZt1/2 by 50%, and more than doubled the CBZClwithout a significant change in theVd. Autoinduction is one explanation for these changes with chronic CBZ therapy. With the addition of VPA to chronic CBZ therapy no change was noted on thet1/2,Cl, Vd, or mean CBZ plasma level, but the CBZ-EP plasma level more than quadrupled. This suggests a decrease in CBZ-EP clearance. These data support the autoinduction phenomena for chronic CBZ therapy and the concept of VPA inhibiting carbamazepine-epoxide metabolism.

ISSN:0163-4356    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Immunoreactive digoxin-like activity was observed in Chinese medicine, KYUSHIN tablet, taken popularly in Japan without prescription. The antibodies used in the assays of digoxin reacted with Chan-su, the major effective component of KYUSHIN, which contained cardiotonic steroids with similar chemical structure as digoxin. One tablet of KYUSHIN had digoxinlike immunoreactivity equivalent to 1.9, 1.5, and 72μg of digoxin measured by three different commercial kits. These different equivalences may be attributed to differences in cross-reactivity of the antibody used in the immunoassays. Two healthy volunteers took two KYUSHIN tablets three times a day, a typical dose, and digoxin-like immunoreactivity reached almost 0.4 μg/L in 0.5 day. Therapeutic drug monitoring should be interpreted carefully in patients taking Chinese medicines, many of which contain the Chan-su component.

ISSN:0163-4356    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Our objective was to evaluate the effectiveness of a computer program to predict daily prothrombin time (PT) response to warfarin therapy using prospectively collected data. The program's predictive performance (precision) and accuracy (bias) were evaluated using fraction mean absolute error and fraction mean error, respectively. We analyzed data from 40 patients using from zero to nine PT feedbacks. The fraction mean absolute error varied from 0.058 to 0.13. The program utilized a pharamocokinetic/pharmacodynamic Bayesian forecasting system to predict prothrombin response.

ISSN:0163-4356    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Drug concentration monitoring (DCM) has become a widely used tool in clinical medicine. However, optimal benefit from this service is most likely if there is close adherence to specific guidelines governing the initiation of, interpretation of, and clinical response to each DCM request. This study was designed to identify deficiencies in the clinical utilization of the DCM service at St. Vincent's Hospital, Sydney, and to test the effect of an intervention process designed to correct these deficiencies. Audit criteria describing appropriate indications for DCM, clinical data required to interpret DCM results, and actions to be taken in response to a result outside the therapeutic range were used to assess the performance of DCM. The results obtained from the baseline survey were used to devise educational material for the resident medical staff and to assist in the revision of the DCM request form. There was a clinically and statistically significant increase in the number of DCM results that satisfied the audit criteria after the intervention process.

ISSN:0163-4356    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

A new set of guidelines for the administration of gentamicin was developed by estimating steady-state peak and trough gentamicin concentrations for simulated patients with known weights and creatinine clearances. The most appropriate doses to achieve target peak concentrations of 5–10 mg/L and troughs of

ISSN:0163-4356    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Accessing patient's veins for drug level sampling is not always feasible. The use of capillary sampling techniques is often utilized when venous access is hampered. In the therapeutic monitoring of patients, unexpected drug level results often occur that can be caused by a number of different factors. The possibility that differences in assay results might occur if samples were collected by capillary stick vs. venous phlebotomy was examined by simultaneous sampling in 18 patients. Although correlation was very high (0.999) and percentage differences fairly low (range of 0 to 15.4%), a statistical difference was noted in the sampling methods. The precision was 6.5 ± 6.58% and there was a slight negative bias (-3.76%), with capillary samples less than venous samples. Although there were statistical differences for the drugs studied in the concentration ranges evaluated, capillary samples should provide fairly small errors when compared to venous samples.

ISSN:0163-4356    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Highly specific and sensitive antisera for fluphenazine-N4‘-oxide (FLUNO) were obtained from New Zealand white rabbits immunized with a bovine serum albumin conjugate of 7-(3-carboxypropionyl)propchlorperazine-N4’-oxide. One of the antisera was used to develop a radioimmunoassay (RIA) procedure that enabled for the first time the determination of steady-state plasma levels of FLUNO, an active metabolite, in patients treated with oral or intramuscular (i.m.) fluphenazine (FLU). This method has sufficient sensitivity to quantitate accurately 20 pg of FLUNO in 200 μl of plasma extract with a coefficient of variation of less than 8%. The antiserum had negligible cross-reactivity (N-deshydroxyethyl-FLU. To confirm that the developed RIA procedure specifically quantitated FLUNO, FLUNO was selectively reduced to FLU by sodium dithionite in plasma samples from patients. A good correlation (r2= 0.9646) was observed between the total FLU level and the sum of FLU and FLU equivalent to FLUNO determined separately in the same plasma. The steady-state plasma concentrations of FLUNO in patients receiving a daily oral dose of 5 to 20 mg of FLU dihydrochloride ranged from 13 to 378% of that of FLU, whereas this value ranged from 10 to 214% in plasma samples from patients treated with a biweekly intramuscular (i.m.) dose of 5 mg of FLU decanoate.

ISSN:0163-4356    

出版商:OVID    

年代:1990

数据来源: OVID