摘要:

Summary: We performed two studies to assess the clinical utility of a Bayesian regression analysis computer program for phenytoin (PHT). In a randomized prospective study of 40 epileptic patients, the dosing program was significantly more accurate (p = 0.002) and less biased (p = 0.02) than a group of physicians at hitting a target PHT serum-concentration. Initial serum PHT concentrations that were not steady state were associated with the largest dosing errors by physicians but did not affect the accuracy of the dosing program. In a second study, we used the dosing program to predict 91 serum concentrations in 31 patients with PHT toxicity after the drug was stopped (initial concentration 26–69 mUg/ml). The program predicted serum concentrations with a mean error of 3.49 \pm 0.29 mUg/ml without significant tendency to over- or underpredict. We conclude that this dosing program may aid clinicians by improving dosing accuracy and predicting serum concentrations in patients with PHT toxicity.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Summary: Tiospirone has demonstrated preclinical activities that predict utility as an antipsychotic drug which lacks the potential to produce extrapyramidal side effects. Indeed, human safety trials after single and multiple dose administration did not reveal the presence of any neurological effects. Serum samples from these studies were obtained for radioreceptor assay to determine the level of dopamine binding activity present. After a single 75 mg dose of tiospirone, demonstrable levels of dopamine binding activity were present. A variety of time points were sampled during the multiple dose study wherein subjects received 60 mg, t.i.d. for 28 days. A comparison of levels of dopamine binding activity present in serum samples taken immediately prior to dosing on various days during the course of the study suggested that steady-state was achieved within seven days with repeated administration. No further rises were seen in the remainder of the study, suggesting that further accumulation of the drug did not occur. Furthermore, hourly monitoring on the last day of drug administration did not reveal any difference, relative to the first dose, in peak levels, time to peak level appearance, or rate of disappearance of dopamine binding activity. This suggests that active metabolites do not accumulate nor is there induction of drug metabolism. Plasma levels of tiospirone were also obtained by high-performance liquid chromatography assay at similar time points. With repeated drug administration plasma tiospirone concentrations also achieved a steady state. Statistically significant increases in plasma half-life and area under the time-concentration curve were observed between day 1 and 28. The levels of dopamine binding activity seen after tiospirone administration are comparable to those seen after administration of the clinically-effective antipsychotic haloperidol. Since haloperidol produces extrapyramidal side effects and, in this study, tiospirone did not, it is suggested that the lack of production of such effects by tiospirone is not due to rapid metabolism and absence of dopamine binding activity in serum. Rather, this profile probably reflects some other pharmacologic property of this novel molecule.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Summary: This study compared the analysis of whole blood cyclosporine concentrations measured by fluorescence polarization immunoassay (FPIA) and radioimmunoassay (RIA) polyclonal and monoclonal procedures. Fifteen orthotopic liver transplant patients with a mean age of 39 \pm 11.06 years were included in the study. One hundred thirteen levels were analyzed using FPIA, RIA polyclonal, and RIA monoclonal procedures. There was no difference statistically in comparing FPIA and RIA polyclonal results (p > 0.05). There was a statistical difference between FPIA and RIA monoclonal results (p = 0.0001). With use of least squares simple linear regression analysis, FPIA results showed good correlation with RIA polyclonal results (R2= 0.87). Poor correlation was shown between FPIA and RIA monoclonal results (R2= 0.51). In this study population, FPIA produced results 2.5% higher than the RIA polyclonal procedure.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Summary: Therapeutic drug monitoring (TDM) can be an effective way to improve care, but only if accurate medication and clinical information necessary to interpret results is available. A multidisciplinary team consisting of medical technologists, clinical pharmacists, and physician pharmacologists is described in detail. This service analyzes and interprets more than 20,000 concentrations per year, most of which are interpreted by specially trained medical technologists. A description of the interactions between members of the team is presented, including qualifications, selection, and training of medical technologists. The outcome of the TDM service from reporting of drug concentrations to daily quality assurance activities is described, as are the benefits of this model relative to other published, mostly pharmacy-based services. A case is made for the routine involvement of specially trained medical technologists in the collection of data and interpretation of drug concentrations.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Summary: The solubility and stability of amphotericin B in human serum in vitro was assessed using a sensitive high performance liquid chromatographic technique. The solubility of amphotericin B at concentrations ranging from 0.5 mUg/ml to 10 mUg/ml in human serum at pH 7.4, at 37dGC, and in 5% CO2(simulated in vivo conditions) showed no significant difference compared with the solubility at 23dGC in room air after a 1 h incubation period. Dissolution of the colloidal suspension at a concentration of 2 mUg/ml reached 81% in 3 min with a small increase in solubility by 60 min. Amphotericin B was very stable (<5% loss) in human serum at −20dGC for up to 14 days with only a 10% loss of drug at 6 months. In dimethylsulfoxide, however, losses at 6 months were >60%. We conclude that amphotericin B solubilizes, but not completely, from a colloidal form in human serum under simulated in vivo conditions at 37dGC and at 23dGC in room air over 1 hour. Additionally, amphotericin B is stable in frozen serum for 6 months.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Summary: A high-performance liquid chromatography (HPLC) procedure used to quantitate encainide and two of its active metabolites,O-desmethylencainide (ODE) and 3-methoxy-O-desmethylencainide (MODE), is described. All three compounds were simultaneously extracted from urine and serum using an octyl (C-8) solid-phase extraction column. The compounds were then separated by reverse-phase HPLC on a cyanopropylsilane column using ultraviolet detection at 260 nm. Serum samples were quantified over a concentration range of 25–400 ng/ml and urine over a range of 150–10,000 ng/ml. Total run time for the assay was <12 min. Within-day and between-day precision and relative error were <10% in serum and <13% in urine for all three compounds. The lower limit of quantitation was 10 ng/ml for encainide and ODE and 15 ng/ml for MODE. This HPLC procedure represents a quick and reliable method of measuring encainide and its major metabolites in both urine and serum, making the assay applicable as an aid for therapeutic drug monitoring of patients receiving encainide therapy.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Summary: The initiation of a liver transplant program in a pediatric hospital prompted the development of a high-performance liquid chromatography method for monitoring cyclosporine, which requires minimal amounts of blood and produces fast, reliable results. A protein-free filtrate is prepared by mixing 250 mUl of whole blood with 750 mUl of organic solvent (acetonitrile and methanol in the ratio of 9:1) containing the internal standard cyclosporine D. After centrifugation the supernatant is subjected to a quick clean-up using two types of disposable cartridges (C18 and silica Bond Elut), and the eluate is dried, reconstituted in equal parts of acetonitrile and water, and subjected to a final heptane wash to remove late eluting peaks. Chromatography is performed at 75dGC using a supelcosil C18 column (15 cm x 4.6 mm) with 3 mUm packing and a mobile phase of 77/23 of acetonitrile/phosphate buffer at pH 2.5. Flow rate is 0.6 ml/min, providing a chromatography time of 10 min. Absorbance is measured at 214 nm at a sensitivity setting of 0.01 absorbance units full scale. Recovery for cyclosporine A is between 92 and 104%, and the lower level of sensitivity is 15 mUg/L. Between-day precision provided coefficient of variation values <5% for a control serum of 150 mUg/L. The method is linear to 3,000 mUg/L. No interfering substances have been found. The method has proved to be consistent, reliable, and simple enough to be performed by all staff members. Column life for a system used daily is at least 3 months.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Summary:N-Desmethylmethsuximide (NDM), the active metabolite of the antiepileptic agent methsuximide, has been analyzed by gas-liquid chromatography and high-performance liquid chromatography (HPLC) in the past. This study compares methods using two commercially available immunoassays for ethosuximide, the enzyme multiplied immunoassay technique (EMIT) and fluorescence polarization immunoassay (FPIA), with an HPLC method for the measurement of NDM concentrations in serum. Within-day precision studies, utilizing low therapeutic (15.0 mg/L) and toxic (45.0 mg/L) NDM concentrations (n = 20), resulted in coefficients of variation (CVs) of 4.6 and 4.2%, respectively, for EMIT and 5.4 and 3.2%, respectively, for FPIA. Day-to-day precision studies (n = 10) resulted in CVs of 7.6 and 5.5%, respectively, for EMIT and 3.5 and 2.4%, respectively, for FPIA. No interference was observed from toxic concentrations of acetaminophen, caffeine, carbamazepine, methsuximide, phenobarbital, phensuximide, phenytoin, primidone, salicylate, and valproic acid in the EMIT and FPIA procedures. There was good linear correlation between EMIT and HPLC NDM determinations of 50 patient samples (r= 0.970; y = 0.96 x + 0.03), and a similar correlation between FPIA and HPLC NDM determinations in 48 patient samples (r= 0.975; y = 0.91 x + 1.24). Using ethosuximide reagents, both EMIT and FPIA systems can be adapted to reliably measure NDM serum concentrations.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Summary: Analysis of serum pentobarbital concentrations in 28 specimens from Reye's syndrome patients was conducted with modifications of three nonspecific immunoassay procedures originally designed to detect barbiturates in serum or urine. An adaptation of the urine enzyme-multiplied immunoassay technique (EMIT) Dupont aca barbiturate screen to the quantitation of serum pentobarbital is described. Replicate analysis of control specimens containing pentobarbital across a wide spectrum of concentrations revealed a between-day precision of <6%. Regression analysis revealed excellent agreement with a high-performance liquid chromatography (HPLC) method: (HPLC) = 0.98 (aca) – 0.07 (r = 0.97). Multiple linear regression analysis with a serum EMIT barbiturate screen and a urine fluorescence polarization immunoassay screen modified to quantitate pentobarbital in serum revealed excellent agreement among all methods, demonstrating that immunoassays offer a reliable approach to pentobarbital quantitation.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Summary: Pentoxifylline, a hemorheologic agent, and its metabolites are structurally similar to theophylline and other xanthines; therefore, they have the potential to interfere with serum assays for theophylline. Any false elevation of theophylline serum concentrations could have a significant impact on drug therapy decisions. Serum was obtained from six elderly subjects who had been taking 400 mg of pentoxifylline three times daily for at least six months. A serum assay using the TDx fluorescence polarization immunoassay failed to detect any measurable amount of theophylline. Normal doses of pentoxifylline and the resulting metabolites do not appear to interfere with the TDx method of serum assay for theophylline.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID