摘要:

SummaryA high-performance liquid chromatography method has been developed for simultaneous determination of doxapram and its metabolites including keto-doxapram, the main and only active metabolite. The aim of the study was to evaluate this microtechnique and to report the cases involving severe adverse effects to determine toxic plasma levels in neonates. The method was found to be selective, and showed a good baseline separation of doxapram and metabolites. Recovery, linearity, intraday/interday precision, and limit of detection determined in aqueous solutions and in spiked plasma were satisfactory. The assay is simple, rapid, and plasma-sparing, which represents a true advantage in managing neonates. Case analysis was performed in two consecutive periods: 124 preterm infants in the first period and 173 in the second period. Severe toxic effects were observed in 4 cases in the first period, with doxapram plus keto-doxapram levels 9 mg/L. In the second period, only one case was observed. High-range plasma concentrations were significantly less frequent in the second period than in the first one. The authors conclude that measuring doxapram plus keto-doxapram in plasma may be of interest to avoid severe toxic effects in preterm neonates treated with doxapram.

ISSN:0163-4356    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

SummaryThe authors evaluated a new Cassette Serum Barbiturates fluorescence polarization immunoassay (FPIA) on the COBAS INTEGRA. The assay was calibrated with secobarbital standards at 0, 0.5, and 4.0 &mgr;g/mL. The assay range was 0.030 to 80 &mgr;g/mL using an automatic 1/20 postdilution feature. Precision was established for two COBAS INTEGRA instruments for ten days by assaying secobarbital target concentrations ranging from 0.125 to 2.2 &mgr;g/mL. The coefficients of variation (CV) for the above target concentrations for the first instrument ranged from 2.7% to 8.3%, and for a second instrument, 3.8 to 8.3%. Seven clinically elevated bilirubin samples were spiked with 0.46 and 1.77 &mgr;g/mL secobarbital. Bilirubin interference was less than 10.9 and less than 7.9%, respectively. The average recovery ranged from 85% to 94%. The mean difference in recovery in serum versus plasma was ≤3%. Fifty-two clinical samples were analyzed for butalbital, pentobarbital, secobarbital, and phenobarbital by GC/MS, and the results were compared to the new Cassette Serum Barbiturates FPIA. The diagnostic sensitivity and specificity were 95% and 100%, respectively. Both FPIA and GC/MS assays are clinically efficacious for monitoring serum barbiturates.

ISSN:0163-4356    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

SummaryA simple, rapid, sensitive, and reproducible high-performance liquid chromatographic (HPLC) method for simultaneous determination of the antiepileptic drugs (ethosuximide, primidone, lamotrigine, phenobarbital, phenytoin, and carbamazepine) and two metabolites (carbamazepine-diol and carbamazepine-epoxide) in human plasma is described. The procedure involves extraction of the drugs from human plasma (100 &mgr;L) with ether using 9-hydroxymethyl-10-carbamyl acridan as an internal standard. The extract was evaporated and reconstituted with mobile phase and then injected onto the chromatograph. The drugs and the internal standard were eluted from a Supelcosil LC-18 stainless steel column at ambient temperature with a mobile phase consisting of a 0.01M phosphate buffer/methanol/acetonitrile (65/18/17, v/v/v) adjusted to a pH of 7.5 with phosphoric acid and a flow rate of 1 mL/min. The effluent was monitored at 220 nm. Quantitation was achieved by using peak area ratio of each drug to the internal standard. The intraassay and interassay coefficients of variation (CV) ranged from 2.43% to 6.25% and from 3.02% to 5.85%, respectively. The absolute (extraction) and relative (analytical) recoveries for the drugs ranged from 70.7% to 104.4% and from 88.3% to 106.1%, respectively. Stability tests showed that the drugs were stable in plasma for at least 4 weeks when stored at −20°C. The method was applied clinically for monitoring the AEDs in epileptic patients.

ISSN:0163-4356    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

SummaryTopiramate (TPM) reportedly binds in a saturable manner to erythrocytes but minimally to plasma proteins. Two studies were performed to evaluate this distribution phenomenon. In all studies, TPM was measured with a newly developed, optimized procedure that uses octyldecyl (C-18) solid phase sorbents disks/packed cartridges and a DB-1 methylsilicone capillary gas chromatography (GC) column. Between-run precision coefficients of variation (CVs) (n= 16) ranged from 3.6%–5.6% at concentrations from 3.0 to 15 &mgr;g/mL, with low limit of detection of 0.2 to 0.3 &mgr;g/mL. For the distribution studies, drug-free whole-blood specimens from five healthy adult volunteers were supplemented with TPM and used to test the influence of TPM concentration and HCT differences on the plasma/blood (P/B) distribution ratio of TPM. In study A, TPM concentration was varied (1–15 &mgr;g/mL) and HCT remained constant (40% ± 5%). In study B, TPM (3 &mgr;g/mL) was added to blood specimens comprising a range of HCT values (20%–40%). Study A results were: mean TPM P/B ratios: 0%, 14.2% ± 5%, 44.2% ± 4%, 76% ± 5.5% at 1, 3, 5, 15 &mgr;g/mL, respectively. Data between each group were statistically different (p < 0.001). Study B results were: mean TPM P/B ratio: 17.3% ± 7.3%, 27.5% ± 10.1%, 39.8% ± 8% and 56.1% ± 8.8% at HCT values of 40%, 32%, 26.5%, 20%, respectively. The TPM P/B ratio was significantly inversely correlated to HCT (r= −905, p < 0.001). TPM P/B partitioning was not temperature-dependent. Researchers concluded that the saturable binding of TPM to RBC is significant and is correlated to HCT. As a result, TPM in the plasma fraction of whole blood will increase when HCT decreases and as total TPM concentration in whole blood increases.

ISSN:0163-4356    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

SummaryThe effect of the new antidepressant reboxetine on the activity of the cytochrome P450 (CYP) 2D6 isoenzyme was investigated in 10 healthy volunteers using dextromethorphan as a model CYP2D6 substrate. Each volunteer received a single 30 mg oral dose of dextromethorphan on three different occasions separated by an interval of at least 4 weeks: a) in a control session; b) after 1 week of treatment with reboxetine, 8 mg/day; and c) after 1 week of treatment with paroxetine (an inhibitor of CYP2D6 activity) 20 mg/day. Urine was collected over the next 8 hours for the determination of the dextromethorphan/dextrorphan metabolic ratio. All subjects were classified as extensive metabolizers (EM) with a dextromethorphan/dextrorphan ratio <0.3. There were no notable changes in the urinary dextromethorphan/dextrorphan ratio in the reboxetine phase as compared to the control session. By contrast, there was a statistically significant increase in the metabolic ratio in the paroxetine phase (p < 0.001), with 4 subjects switching to poor metabolizer (PM) phenotype. These results suggest that reboxetine is unlikely to cause clinically significant interactions with substrates of CYP2D6.

ISSN:0163-4356    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

SummaryA 35-year-old man with schizophrenia was successfully treated with clozapine at a daily oral dose of 700–725 mg for more than 7 consecutive years. Two weeks after abrupt cessation of chronic heavy cigarette smoking, he suddenly developed tonic clonic seizures followed by stupor and coma. After 2 days of intensive care, the patient recovered completely but could not recall the episode. Clozapine therapy was reinstituted and could be carried out successfully at 425 mg daily, i.e., at an approximately 40% reduction of the daily dose before he stopped smoking. The sudden cessation of smoking most likely caused a rise in plasma concentrations of clozapine and/or clozapine metabolites resulting in the seizure episode. A likely mechanism is that the heavy smoking had induced cytochrome P450-1A2, the main enzyme involved in the metabolism of clozapine.

ISSN:0163-4356    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0163-4356    

出版商:OVID    

年代:1999

数据来源: OVID