摘要:

We evaluated the efficacy, development of adverse effects, and possible correlation between the plasma concentration of carbamazepine (CBZ) and its major metabolite, carbamazepine-10,11-epoxide (CBZ-E), in a group of epileptic patients in whom selective increases in CBZ doses were made. Eighteen patients with refractory partial epilepsy participated in an open trial. Five were on monotherapy and 13 on poly therapy. All the patients were on CBZ before the trial and had plasma levels within the therapeutic range (17–42 μmol/L). After a baseline period, CBZ doses were progressively increased either to reach a 50% reduction in seizure frequency for 2 months or until side effects appeared. Thirty-nine percent of the patients had a 50% decline in seizure frequency, but only 17% improved for >6 months. Mild or moderate side effects were observed in 78% of the patients. Side effects were correlated with CBZ plasma levels but not with CBZ-E plasma levels. Correlation between CBZ and CBZ-E plasma levels were found in the monotherapy group, but not in the polytherapy group. Our results confirm that higher doses of CBZ can successfully be used in some patients with refractory partial epilepsy. Furthermore, the plasma level of CBZ-E does not seem to be a useful indicator of toxicity in CBZ-treated ambulatory epileptic patients.

ISSN:0163-4356    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The aim of our study was to find a therapeutic range for the serum concentration of zuclopenthixol (S-Zu) in chronic schizophrenic patients. S-Zu was measured in 17 patients and dosage reduction was suggested by the laboratory if S-Zu exceeded 15 nmol/L. The clinical symptoms and side effects were evaluated blindly using the Brief Psychiatric Rating Scale (BPRS) and the UKU rating scale, respectively. S-Zu and ratings were repeated 6, 12, and 24 weeks after the final dosage adjustments. In 7 of 10 patients with S-Zu >15 nmol/L the dosage was reduced by 20–67%. After dosage reduction the S-Zu was below 15 nmol/L in 10 of the 17 patients. The mean BPRS score and the side effects, evaluated by the UKU scale, were reduced in patients in whom the dosage was reduced. It is suggested that S-Zu in the range 5–15 nmol/L may serve as a preliminary therapeutic range for S-Zu.

ISSN:0163-4356    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Erythromycin is a strong inhibitor of cytochrome P450 [CYP3A4] and has a potentially dangerous interaction with midazolam and triazolam. The possible interaction between erythromycin and a short-acting benzodiazepine, temazepam, was investigated in a double-blind, randomized crossover study. Ten healthy volunteers received 500 mg erythromycin or placebo orally three times a day for 6 days followed by a challenge dose of 20 mg temazepam. Plasma samples were collected for the determination of temazepam, oxazepam, and erythromycin, and psychomotor effects were measured during the 24 h after intake of temazepam. Erythromycin did not change the pharmacokinetics or pharmacodynamics of temazepam to a statistically significant degree. The metabolic fate of temazepam and its almost complete bioavailability explain the lack of interaction. Temazepam, unlike midazolam or triazolam, can thus be prescribed in the usual doses for patients receiving erythromycin.

ISSN:0163-4356    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Prior authors had hypothesized (but not clearly found) an increased apparent volume of distribution (Vd) for gentamicin in neonates undergoing extracorporeal membrane oxygenation (ECMO). We chose to study the question in our own clinical setting. To develop population pharmacokinetic models of the drug, we used the nonparametric expectation and maximization population modeling method and data from 11 neonates who received gentamicin on ECMO, including 6 infants who received gentamicin both on and off ECMO for severe respiratory failure. We found an increased Vdfor gentamicin on ECMO and attributed much of the difference from prior investigations to our use of an explicitly determined laboratory assay error pattern for the measured serum concentrations rather than using constant weighting of the serum level data points. For six infants, while on ECMO their median Vdwas 0.748 L/kg compared with a median Vdof 0.471 L/kg after ECMO was discontinued. The median clearance of gentamicin in the six infants while undergoing ECMO was 0.239 L/h compared with 0.350 L/h after ECMO was discontinued. The median half-time (T1/2) was 9.24 h while on ECMO compared with 3.87 h when off ECMO. We conclude that while undergoing ECMO, neonates have a higher volume of distribution for gentamicin, a lower clearance, and a much longer half-life. Based on these results, for attainment of the desired peak-and-trough plasma gentamicin concentrations for infants undergoing ECMO (i.e., 5–8 and <2.0 μg/ml, respectively), we now recommend a loading dose of ∼4.3 mg/kg of gentamicin and a maintenance dose of ∼3.7 mg/kg to be given at dosing intervals of 18–24 h, followed by monitoring of serum concentrations and appropriate dose adjustments thereafter. To attain alternative goals, the model provides different loading and maintenance doses.

ISSN:0163-4356    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

A limited sampling strategy for determination of the area under the plasma concentration versus time curve (AUC) of methotrexate (MTX) in patients with rheumatoid arthritis (RA), treated with weekly oral doses, has been validated. Stepwise linear regression analysis was used for optimal inclusion of data points in mathematical models to estimate AUC. A new plot for evaluation of the accuracy and precision of the estimated AUC values was introduced in the present study. By plotting the ratio of determined/estimated AUC values versus estimated AUC values, the influence of number of sampling points on the precision and accuracy of estimated AUC values was easily validated. Our results show that AUC values of MTX in RA patients can be estimated from a single plasma sample at 3 h or preferably, due to increased precision, by additional samplings at 5 and 1 h. A further increase of the number of sampling points increased the precision of the AUC estimates only to a minor extent. The accuracy of the estimated AUC values was independent of the number of sampling points. A limited sampling procedure can now be used for further studies on the relationship between MTX levels and its effects.

ISSN:0163-4356    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

A detailed questionnaire was distributed to the 30 Australian laboratories known to provide cyclosporin-A (CsA) therapeutic drug monitoring (TDM) services with a view to evaluating the range of approaches to such monitoring. Replies were received from all 30 laboratories. The data suggested there was a wide discordance in approaches to CsA TDM due to the fact that laboratories appeared to have adopted individual approaches to this service, both in method selection(s) and proposed therapeutic range(s). In many cases, patients served were shown to travel to more distant centers for their graft, returning to their home city/town for longer term management. Hence, services of several laboratories were involved during their clinical care. A strong mandate was received from respondents for development of national guidelines for the monitoring of CsA and other immunosuppressant drugs in order to avoid such discrepancies in the future. The approaches to external analytical quality assurance (QA) and, to a lesser extent, internal quality control (QC) were generally inadequate.

ISSN:0163-4356    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Cyclosporin-A (CsA) therapeutic drug monitoring plays an integral role in therapeutic management of immunosuppressed patients, including those with organ transplants. This communication, prepared by an Australian team, presents recommendations for the routine monitoring of CsA, including blood sampling methodological approaches and interpretation of results generated. The consensus approach described is intended to address the diversity of attitudes to CsA monitoring demonstrated in a recent national survey of Australian laboratories that provide CsA analyses.

ISSN:0163-4356    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Two methods for the quantitative determination of imipramine (IMI) and desipramine (DMI) by fluorescence polarization immunoassay (FPIA) are described. One immunoassay allows for the accurate quantification of imipramine in the presence of desipramine, while the other allows for the accurate quantification of desipramine in the presence of imipramine.

ISSN:0163-4356    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The stability of indocyanine green (ICG) in human serum after storage at −20 and −70°C for an extended time was studied. Serum samples were fortified with ICG at 6.5, 2.0 and 0.3 μg ml−1aliquoted, and frozen at −20 or −70°C. The analytic methodology used an internal standard and separation on a reverse phase liquid chromatographic column with UV detection at 240 nm. Samples were prepared for analysis by protein precipitation with acetonitrile. The assay was stability indicating as shown by the complete loss of the ICG peak upon storage at −20°C for 8 weeks. ICG was not stable, as determined by a t test, for 1 week in human serum when stored at −20°C. Storage at −70°C improved stability but the ICG concentration began to fall steadily after 4 weeks of storage.

ISSN:0163-4356    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

A gas-liquid chromatographic method for the simultaneous measurement in serum of bupivacaine, lidocaine, and their main metabolites, 2,6-pipecolylxylidide (PPX) and monoethylglycine xylidide (MEGX), respectively, is described. The procedure involves a one-step extraction and injection of the extract into a gas chromatograph equipped with a capillary column and nitrogen phosphorus detector under constant temperature conditions. Recovery of all components averaged 94%, with the lowest detection limit of 15 ng/ml for the four drugs. The precision within-series coefficients of variation ranged from 7.7% for bupivacaine, 8.6% for lidocaine, 10.2% for MEGX, and 15.8% for PPX. The interday coefficients ranged from 0.7 to 6.5%. Concomitant use of caffeine and carbamazepine may interfere with MEGX and bupivacaine determination, respectively. For this reason, in patients receiving one of these two drugs (or ingesting foods and beverages containing caffeine), the described method is not recommended.

ISSN:0163-4356    

出版商:OVID    

年代:1994

数据来源: OVID