摘要:

Using equilibrium dialysis and incubation experiments, we determined the binding of moricizine to human plasma, isolated plasma proteins, and erythrocytes. The mean (% ± SD) plasma protein binding at various moricizine concentrations ranged from 81.2 ± 2.1 to 89.9 ± 2.1%. There was no apparent relationship between drug concentration and extent of binding in pooled plasma over the concentration range tested. However, protein concentration-dependent binding was observed with albumin and α1-acid glycoprotein (α1-AGP). The unbound fraction of moricizine fell from 61 to 19% and from 70 to 17% with increasing albumin (5 and 50 g/L, respectively) and α1-AGP (0.2 and 1.2 g/L) concentrations. The binding of moricizine to β-lipoprotein (5 g/L) was 70.6 ± 3.1% and to γ-globulin (12 g/L) was 13.6 ± 3.3%. Moricizine partitioned into erythrocytes, showing an erythrocyte/plasma drug concentration ratio of 1.325 ± 0.070 and erythrocyte/buffer ratio of 8.561 ± 0.620. An estimation could be made that 57% of total drug in whole blood was associated with erythrocytes, 39% bound to plasma proteins, and 4% was free. The results of this study demonstrated that erythrocytes, albumin, and α1-AGP were the major binding components in blood.

ISSN:0163-4356    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Roxithromycin is a semisynthetic macrolide antibiotic having similar in vitro antibacterial profile and potency to erythromycin but possibly greater in vivo potency. The single and multiple oral dose pharmacokinetics of roxithromycin and erythromycin were studied in 12 healthy volunteers. Plasma concentrations of the two compounds were measured by a sensitive and specific high-performance liquid chromatographic method using electrochemical detection. After single doses, roxithromycin 150 mg gave a Cmax3.3-fold higher and an area under the curve (AUC) 16.2-fold higher than erythromycin 250 mg. The half-life for roxithromycin was 12.42 ± 3.94 h compared with 1.53 ± 0.42 h for erythromycin. On multiple dosing, the AUC over a dosing interval for erythromycin (250 mg, six hourly doses) was increased 2.3-fold compared with the single dose, whereas that for roxithromycin (150 mg, 12 hourly) was decreased by 25.4%. Because of these opposing changes during chronic dosing, the average plasma roxithromycin concentration over the dosing interval was 2.6-fold higher than that for erythromycin, which was a smaller excess than would have been predicted from the single dose data. The results suggest that roxithromycin exerts less inducing and inhibiting effects on human cytochrome P450 than erythromycin. Roxithromycin has a favorable pharmacokinetic profile suitable for twice daily dosing and may have a lower potential than erythromycin for cytochrome P450-mediated drug interactions.

ISSN:0163-4356    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Therapeutic drug monitoring (TDM) is commonly employed to optimize the dosing of certain drugs, including digoxin, aminoglycosides, theophylline, and phenytoin. Studies were reviewed in order to (a) evaluate the effect of TDM on the occurrence of toxic drug reactions (TDRs) and (b) identify factors that may modify or invalidate the relationship. In 14 studies, monitored patients suffered fewer toxic drug reactions than nonmonitored patients (odds ratio = 0.35, 95% confidence interval, 0.13 to 0.89). The average effect size was larger in studies that utilized a control group for comparisons rather than a before-and-after study design. TDM appeared to be most beneficial for patients taking theophylline or digoxin. Issues that must be addressed in future TDM service evaluations include (a) study design, (b) adverse patient selection, (c) insufficient sample size, (d) incomplete or inconsistent description of the TDM service, and (e) incomplete, inconsistent, or absent description of criteria for reporting TDRs.

ISSN:0163-4356    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

This study describes an aminoglycoside dosing service in a community hospital. Between 95 and 98% of all aminoglycoside doses are calculated by staff pharmacists using traditional pharmacokinetic equations. All patients dosed by the pharmacy are then monitored by clinical pharmacists who make necessary dosage modifications following serum peak and trough levels. After the first year of this service, it was determined that a slight change in the volume of distribution equation would allow the pharmacy to calculate maintenance doses that would more accurately result in estimated serum peak and trough levels. Physicians are pleased with this service and professional job satisfaction is experienced by the pharmacists. Therapeutic drug monitoring is an important component of patient care and can be implemented in community hospitals. Other pharmacy departments are encouraged to establish similar services.

ISSN:0163-4356    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Although current immunoassay kits for digoxin supposedly have antibodies of high specificity, serum digoxin levels in patients taking spironolactone suggest that spironolactone interferes with the determination. In vitro determinations of digoxin performed on blank serum spiked with spironolactone and its metabolite canrenone showed that contrary to the belief gained from reading the manuals of some diagnostic immunoassay kits, spironolactone significantly influences digoxin determinations.

ISSN:0163-4356    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The stability of phenytoin in blood collected in plain and serum separator tubes (SSTs) was investigated under simulated storage and transport conditions. The drug was generally more stable in plain collection tubes than in SSTs. No degradation occurred in plain red-top tubes or in refrigerated SSTs, but clinically significant degradation was present in SSTs stored at room temperature (25°C) and at elevated temperature (32°C) 24 h after collection. The mean loss was 17.9% at 25°C and 25.9% at 32°C. It is recommended that if blood is to be transported or stored in SSTs, the samples be refrigerated unless assay can be performed within 8 h.

ISSN:0163-4356    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Felbamate is an investigational antiepileptic drug (AED) in clinical trials. A high-performance liquid chromatographic method for the simultaneous analysis of felbamate, phenytoin (PHT), 5-(p-hydroxyphenyl)-5-phenylhydantoin, carbamazepine (CBZ), carbamazepine-10,11-epoxide, and carbamazepine-10,11-diol in serum was developed by a mobile phase optimization technique. Capacity factors for the compounds of interest and 12 other AEDs and metabolites were determined with mixtures of methanol, acetonitrile, or tetrahydrofuran and a 0.01Mammonium phosphate buffer, pH 6.5, on a reversed-phase C8column. An optimized mobile phase composition was determined that could separate the compounds of interest and three internal standards in <15 min. Serum was extracted with CH2Cl2/ethyl acetate (2:1) after addition of three internal standards. The method was validated for within-day and between-day precision and accuracy for the six compounds. Coefficients of variation were generally <10% at all concentrations and <5% in the typical therapeutic range for each compound. The lower limit of detection was estimated at 0.2 μg/ml for CBZ and its metabolites and 0.5 μg/ml for felbamate and PHT. For felbamate, the lowest point on the standard curve was 1.88 μg/ml with a between-day variability of 10.3%. The assay was used to determine the serum concentrations of PHT and CBZ and its metabolites in a subject before, during, and after felbamate therapy.

ISSN:0163-4356    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

A simple, sensitive, and reproducible high-performance liquid chromatrography assay is described for the simultaneous determination of dextromethophan, dextrorphan, 3-hydroxymorphinan, and 3-methoxymorphinan in plasma and urine. A conventional solvent-solvent extraction procedure was used for the isolation of the analytes from plasma and urine samples. The compounds were separated on a cyano column (150 x 4.6 mm, 5-μm particle size) using a mobile phase of acetonitrile/triethylamine/distilled water (17:0.06:82.94, vol/vol), pH 3.0, and then were measured by fluorescence detection. Calibration curves in the range 2–200 ng/ml for plasma and 0.05–10 μg/ml for urine were linear and passed through the origin. The precision and accuracy were >90% and the lowest detectable concentrations were 0.5 ng/ml for 3-hydroxymorphinan and 3-methoxymorphinan and 1 ng/ml for dextromethorphan and dextrophan in plasma. The utility of this method is demonstrated in a preliminary study of dextromethorphan metabolism and pharmacokinetics in man.

ISSN:0163-4356    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Captopril is an orally active inhibitor of angiotensin-converting enzyme. A rapid, accurate, and sensitive high-performance chromatography (HPLC) method is described for measuring plasma concentrations of captopril. Captopril was stabilized by forming an adduct withp-bromophenacyl bromide. This adduct was measured by HPLC using a C-18 reverse-phase column and monitoring the column effluent by ultraviolet absorption at 260 nm. The method proved to be linear in the clinical range of 10–1,000 ng/ml. The plasma levels of captopril in a young patient given a small oral dose were determined by this method.

ISSN:0163-4356    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The effect of a hypocaloric, low protein diet on theophylline kinetics was studied in a 70-year-old man with chronic obstructive pulmonary disease who lost 6.2 kg of weight. Total systemic clearance, unbound clearance, and intrinsic hepatic clearance fell dramatically. Theophylline elimination half-life rose from 8.4 to 17.1 h. Therefore, a diet deficient in both calories and protein can significantly impair theophylline clearance and prolong theophylline elimination half-life.

ISSN:0163-4356    

出版商:OVID    

年代:1990

数据来源: OVID