摘要:

A simple, rapid, and reliable procedure for the determination of ethylene glycol (EG) and other diol compounds utilizing direct injection of diluted serum on a unique wide-bore capillary column containing a highly polar stationary phase (Nukol column) is presented. The method uses 1,4-butanediol as the internal standard (IS) and resolves propylene glycol, EG, 1,3-butanediol, and diethylene glycol. The within-run precision of the method yielded at 27.5 mg/L EG, CV = 9.4% (n = 10) and at 222 mg/L EG, CV = 7.3% (n = 10). Absolute recovery of EG at 222 mg/L was 95.9 ± 7.1% (n = 10). At the limit of quantitation, 27.5 mg/L EG, the absolute recovery was 115 ± 13.1% (n = 10). The method was free of interference from common volatile intoxicants, organic acid metabolites, and polar drugs. However, valproic acid was not completely resolved from the IS. The Nukol column has demonstrated an extended column lifetime and versatility for analysis of other polar compounds.

ISSN:0163-4356    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Attempts to investigate relationships between plasma levels of neuroleptics and therapeutic outcome in schizophrenic patients have been hampered due to such factors as the chemical nature of these drugs, their metabolism, and the very heterogeneous nature of the disease states. Two clinical studies are described that investigate the relationship between plasma levels of fluphenazine (FLU) and its metabolites and therapeutic outcome in schizophrenic patients. In the first of these studies the levels of FLU and fluphenazine sulfoxide (FLUSO) in schizophrenics receiving either 5 or 25 mg of fluphenazine decanoate (FLUD) intramuscularly every 2 weeks were monitored. Patients given 25 mg of FLUD required 3 months to reach plasma level steady state. The results suggest that such patients, when being switched from the oral to the depot formulation of FLU, should continue to receive oral supplementation during the 1st 3 months after conversion. The relationship between log-transformed plasma levels at 26 and 38 weeks with subsequent psychotic exacerbation was investigated with the use of logistic regression and survival analysis. Both demonstrated significant relationships between FLU plasma levels and a risk of psychotic exacerbation at 26 and 38 weeks. The possibility of any correlations between neurological side effects and plasma concentrations were also investigated, with statistically significant correlations between FLU levels and akinesia found at 2 and 26 weeks. In the second of these studies the levels of FLU, FLUSO, 7-hydroxyfluphenazine (7-OHFLU), and fluphenazineN4‘-oxide (FLUNO) in schizophrenics receiving 5, 10, or 20 mg of oral fluphenazine dihydrochloride daily for 4 weeks were monitored. The relationships between log-transformed plasma levels, disabling side effects, and global improvement were examined by logistic regression for the 4-week period. The study showed a significant correlation between increases in both plasma levels and disabling side effects such that at a plasma level of 2.7 ng/ml, approximately 90% of acutely ill patients experienced disabling side effects. Conversely, the study also showed that at a plasma level of 0.67 ng/ml, 48% of patients experienced improvement without the development of disabling side effects. When relationships between metabolite levels, disabling side effects, and global improvement were examined by logistic regression, a stronger correlation between disabling side effects and FLUNO levels than between side effects and FLU levels was found. No correlations between disabling side effects and plasma levels of FLUSO or 7-OHFLU were observed. These studies illustrate the usefulness of measuring plasma levels of neuroleptic drugs.

ISSN:0163-4356    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Accurate and early diagnosis of the cause of renal transplant dysfunction is important in successful patient management. Controversy exists as to whether a cyclosporine-specific or -nonspecific method is more predictive of clinical events. In an attempt to answer this question, all episodes of acute renal dysfunction were reviewed in 322 stable renal transplant recipients over a 20-month period. To diagnose the cause of each episode of renal dysfunction, an analysis was made of patient demographics; weight; serum creatinine; cyclosporine dose; cyclosporine level, using a specific method—high-performance liquid chromatography (HPLC)—and a nonspecific method—fluorescent polarization immunoassay (FPIA); changes in cyclosporine dose; renal biopsy; and response to any therapeutic intervention. There were 138 patients, who developed 279 episodes of renal dysfunction. Causes of renal dysfunction were cyclosporine-related (n = 103), acute rejection (n = 63), extracellular fluid volume depletion (n = 27), other (n = 59), and unknown (n = 27). The mean HPLC cyclosporine level was significantly different in patients with acute cyclosporine toxicity (p< 0.001) and patients with acute rejection (p< 0.001) when compared to those with stable renal function; the mean FPIA cyclosporine levels were not significantly different between the three groups. However, a larger percentage of patients with rejection were subtherapeutic when measured by HPLC, while a higher proportion of patients with nephrotoxicity were above the therapeutic range measured by FPIA. These results indicate that parent cyclosporine is most important for immuno-suppressive activity and suggests that cyclosporine metabolites may play a role in toxicity.

ISSN:0163-4356    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Therapeutic drug monitoring is used for the immunosuppressant drug, cyclosporin, even though it is often unclear what concentration should be targetted. At St. Vincent's Hospital, Sydney, a polyclonal, whole blood immunoassay is used to measure cyclosporin and metabolites. The objective of the present study was to audit how the concentration results produced by the laboratory were actually used to adjust dosage. Each transplantation unit was asked about their policy for dosage adjustment and which therapeutic range was used. The audit criteria were considered to be passed if the action taken based on a concentration result was (a) predictable based solely on the concentration and its relationship to the stated therapeutic range (e.g., dosage increased if concentration was below therapeutic range) or (b) based on clinical considerations (e.g., dosage decreased because of increased serum creatinine). Data were collected for the actions taken following 347 concentration results over a 6-week period. Audit criteria were fulfilled for 246 (71%) of the results. The majority of the cyclosporin concentrations (75%) were determined for the cardiopulmonary unit; 66% of these fulfilled audit criteria. Approximately two-thirds of all the cyclosporin concentrations requested were followed up by appropriate action based on stated therapeutic ranges or documented clinical reasons.

ISSN:0163-4356    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

We studied the effect of multiple oral doses of moricizine on the pharmacokinetics of theophylline in healthy male subjects. Twelve subjects initially received two single oral doses of theophylline, one in the form of immediate-release Aminophyllin on day 1 and the other in the form of controlled-release Theo-Dur on day 3. Multiple oral doses of moricizine (Ethmozine, 250 mg every 8 h) began on day 5 and continued for 18 days. While receiving moricizine, the subjects were again given the two formulations of theophylline in the same order on days 19 and 21. Theophylline pharmacokinetic profiles were obtained over 36 h after all theophylline administrations. Multiple-dose moricizine administration significantly decreased (p< 0.0005) theophylline area under the curve by 32 and 36% after Aminophyllin and Theo-Dur, respectively. Theophyllinet1/2was also significantly decreased (p< 0.02) by concomitant moricizine dosing. Moricizine had no apparent effect on theophylline absorption after Aminophyllin, based on the lack of changes in the maximum plasma concentration (Cmax) and the time to reachCmax;however, moricizine administration did decrease (p< 0.0005) theCmaxof theophylline after Theo-Dur. We conclude that these pharmacokinetic changes are most likely due to enzyme induction mediated by moricizine. Consequently, concomitant use of moricizine and theophylline may necessitate the administration of more frequent and higher doses of theophylline.

ISSN:0163-4356    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

In this study, we used solid-phase extraction with Sep-Pak and a liquid-liquid extraction with methylene chloride as two primary methods of extracting FK506 from plasma. The extracts were either analyzed directly by enzyme-linked immunosorbent assay (ELISA) or subjected to high-performance liquid chromatography (HPLC) separation and different fractions were analyzed by ELISA. Serial blood samples were obtained from four kidney transplant patients and four patients who underwent liver transplantation, from day 1 until day 30–35 posttransplantation. There was no significant difference in the FK506 plasma concentration as measured by all four methods in normal transplant patients. However, in liver transplant patients, the solid-phase extraction method gave higher FK506 concentrations than the methylene chloride extraction during the early postoperative period. The concentrations measured after methylene chloride extraction were higher than that after HPLC-ELISA. This higher FK506 concentration measured by direct ELISA could be attributed to possible cross-reacting metabolites that were present in the plasma of patients with abnormal liver functions. Once liver function returns to normal, all four methods give identical plasma concentrations for FK506.

ISSN:0163-4356    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The development of inexpensive in-house reagents for the assay of carbamazepine in serum, using a commercially available derivative and antiserum is described. They were adapted for use on the Abbott TDx as direct replacements for commercial reagents. Comparison with a high-performance liquid chromatography method is discussed together with an evaluation of their performance in an external quality control scheme. They proved robust and reliable and reagent costs were reduced to around 3p per test.

ISSN:0163-4356    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

A specific and sensitive radioimmunoassay (RIA) for the measurement of SQ 33,600 in biological fluids has been developed. The assay utilizes a SQ 33,600 polyclonal antibody, [125I]iodohistamine-SQ 33,600 radiolabel, and standards in serum. Satisfactory zero binding and sensitivity were obtained after an overnight incubation at 4° C. Separation of the antibody-bound and free radiolabel was achieved by employing polyethylene glycol-goat anti-rabbit γ-globulin (PEG-GARG) separant. A quantitative recovery in serum and urine of the exogenous analyte was obtained at all concentrations of SQ 33,600 tested. Intra-assay coefficients of variation (CVs) were 6.19 and 5.57% for the low and high controls, respectively. Interassay CVs were 6.64 and 6.06% for the low and medium controls, respectively. Results from the parallelism studies were acceptable for both serum and urine samples. Comparison of results from samples which were assayed by RIA and high-performance liquid chromatography (HPLC) demonstrated a significant correlation (r= 0.994; HPLC = 1.09 RIA + 57.98; n = 45). The present RIA has been successfully used to assay clinical specimens from pharmacokinetic studies.

ISSN:0163-4356    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

This assay method allows a simultaneous determination of imipramine, desipramine, their 2-hydroxylated metabolites, and imipramine-N-oxide in 0.5 ml of plasma or 0.1 ml of urine within 35 min by an ion-paired, reversed phase (C18) high-performance liquid chromatography (HPLC) with electrochemical detection. The analytes are extracted from alkalinized plasma or urine with 5 ml of a 90/10 mixture (by vol) of diethyl ether/2-propanol, back-extracted into 0.5 ml of 0.1 mol/L phosphoric acid. Urine samples are enzymatically treated with β-glucuronidase/arylsulfatase before extraction. The electrochemical detection is performed with a glassy carbon electrode set at +0.85 V against the Ag/AgCl reference electrode. Recoveries for the analytes and the internal standard (propericiazine) from plasma or urine ranged from 66.4 to 105.7% with coefficients of variation (CVs) of <6.8%. The intra- and interassay CVs for the analytes were <17.4% in plasma and <14.2% in urine. The limits of determination (a signal-to-noise ratio of 3) for imipramine, desipramine, 2-hydroxyimipramine, 2-hydroxydesipramine, and imipramine,-N-oxide were 0.5, 0.3, 0.02, 0.02, and 1.0 μg/L, respectively. Only four of the 23 psychotropic drugs, which might be coadministered with imipramine or desipramine, were considered to be the possible sources to interfere with the assay. We evaluated clinical applicability of this method by determining plasma concentration- and urinary excretion-time courses of the respective analytes in an extensive and a poor metabolizer of the debrisoquine/sparteine-type oxidation after a single oral dose of imipramine HCI (25 mg). The present method appears to be suitable not only for the therapeutic drug monitoring of imipramine and its active metabolites but also for studying the pharmacogenetically related metabolism of imipramine or desipramine.

ISSN:0163-4356    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The control of bovine trypanosomiasis in Africa continues to rely heavily on the chemoprophylactic drug isometamidium (ISMM) chloride. However, despite many years of use, no methods are available that are sufficiently sensitive to measure drug levels in treated cattle. An enzyme-linked immunosorbent assay (ELISA) for the detection of ISMM in the serum of treated cattle has been developed and evaluated. Liquid-phase ISMM (sample) competes with solid-phase bound ISMM-protein conjugate for biotinylated sheep anti-ISMM IgG. The specific IgG is detected by streptavidin-peroxidase, using tetramethylbenzidine for colour development. Assay calibration is by four-parameter logistic curve-fitting. Factors contributing to absorbance variance were considered in assay optimization and improvement of precision and the lower limit of detection (∼0.1 ng/ml in serum). The ELISA was shown to detect serum ISMM for several months after treatment of cattle in a trypanosomiasis endemic country. The potential uses of this assay include the development of rational prophylactic drug regimens, and the indirect detection of drug-resistant trypanosomes.

ISSN:0163-4356    

出版商:OVID    

年代:1993

数据来源: OVID