摘要:

There is an increased use of extracorporeal membrane oxygenation (ECMO) in the last 15 years for critically ill neonates. While receiving ECMO therapy, the critically ill infant needs various medications. We performed an in vitro study to evaluate the potential effect of the membrane oxygenator on drug extraction. Two closed ECMO circuits were set up at rates of 320 ml/min. One circuit was new and the other was used clinically for 5 days. Morphine at 8 ng/ml, gentamicin 10 μg/ml, vancomycin 40 μg/ml, phenobarbital 20 μg/ml, and phenytoin 20 μg/ml were injected into the circuit at 1-h intervals. Blood samples were drawn from the circuit at 10, 30, 60, and 240 minutes after injection. In the new circuit, drugs were eliminated as follows: vancomycin 36%, gentamicin 10%, phenobarbital 17%, phenytoin 43%, morphine 36%. In the used system, levels fell to a much smaller extent: vancomycin 11%, phenobarbital 6%, gentamicin 0%, phenytoin 0%, and morphine 16%. In a child receiving 20 μg/kg/h infusion of morphine, steady-state concentrations of 68.2 ng/ml fell to 11.6 ng/ml after changing the membrane. Our data indicate that the ECMO is associated with lowering of the concentrations of commonly used medications and that this process may depend partially on how new the membrane is. Before these changes may lead to new dosing guidelines for small children receiving ECMO, more experiments with new and used systems are warranted, as well as with different types of ECMO.

ISSN:0163-4356    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

To interpret blood levels of tricyclic antidepressants, we studied the distributions of amitriptyline and nortriptyline in human blood and explored their control by plasma factors. Each compound (300 ng/ml) was added to whole adult blood and to cord blood with decreased α-1-glycoprotein (AGP). Drugs (250 ng/ml) were also added to washed erythrocytes (RBCs) resuspended in autologous plasma or saline (hematocrit = 0.4) with or without AGP, albumin, or tris(2-butoxyethyl) phosphate (TBEP), used to displace AGP-bound drugs. Plasma AGP was determined in all adult blood donors (n = 17). With adult blood, plasma amitriptyline was 393 ± 52 ng/ml, RBC amitriptyline was 184 ± 33 ng/ml. Plasma and RBC nortriptyline were 199 ± 28 and 288 ± 39 ng/ml, respectively. With saline, cellular amitriptyline and nortriptyline were 81 ± 10 and 88 ± 6%, respectively. With plasma, cellular amitriptyline and nortriptyline were 25 ± 8 and 49 ± 10%, respectively. The corresponding cord blood values were 52 ± 12 and 62 ± 6%. Graded increments of AGP in saline reproduced the distribution pattern seen with increasing concentrations of plasma. Albumin did not influence drug distribution. TBEP markedly increased erythrocyte amitriptyline in adult but not in cord blood. Plasma AGP correlated positively (p= 0.031) with the RBC/plasma ratio of amitriptyline. Amitriptyline is predominantly distributed in plasma, nortriptyline in RBCs. This differential distribution is dose dependent and reflects the higher binding of amitriptyline to AGP when compared with nortriptyline. Interpretation of tricyclic antidepressant blood levels is clarified by obtaining assays from RBCs and plasma.

ISSN:0163-4356    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The present study attempted to characterize the distribution of cyclosporin A (CsA) among the lipoprotein fractions, very-low-, intermediate-, low-, and high-density (VLDL, IDL, LDL, and HDL, respectively) in the plasma of patients awaiting heart transplantation and the influence of plasma lipid constituents on the pharmacokinetics of CsA. Major fractions of a therapeutic concentration of CsA were found in HDL and in LDL. In addition, plasma lipid concentrations (total cholesterol, triglycerides, phospholipids, VLDL-cholesterol—TC, TG, PL, VLDLc, respectively) are positively correlated with the CsA distribution within the LDL fraction, and negatively correlated with the CsA distribution within the HDL fraction. Thus, the percentage of CsA in each type of lipoproteins was shown to vary with the lipid levels among individuals. A significant negative correlation was found between apparent distribution volume at steady state (Vss) in plasma and TC, PL, and LDLc and between the area under the curve measured in blood (AUCB) for whole blood and PL.

ISSN:0163-4356    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

In three groups (each n = 12) of unselected hospitalized patients treated either with digoxin, theophylline, or gentamicin routinely performed TDM measurement of trough steady-state plasma levels (+ peak levels in case of gentamicin) was combined with a pharmacokinetic study at steady state (multiple blood sampling during one dosing interval). Pharmacokinetic parameters (apparent volume of distribution Vd, total plasma clearance CL) needed for individualization of dosage were evaluated by the Bayesian approach and a model-(in)dependent pharmacokinetic program (TOPFIT). Comparison of both methods revealed some small differences in the pharmacokinetic parameters for all three drugs. Mean deviations of the Bayesian estimates from the pharmacokinetic calculations of the three drugs ranged between 20 and 38% for Vdand between 13 and 22% for CL, indicating that the Bayesian approach provided reliable pharmacokinetic estimates for individualizing drug dosage under routine conditions. Therefore, it is suggested that routine TDM combined with Bayesian-based analyses can be regarded as an alternative to pharmacokinetic studies in clinically relevant populations.

ISSN:0163-4356    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Theophylline assays performed in a children's hospital were audited, focusing particularly on distribution of plasma concentration values, interpretation of the assay result, appropriateness of the advice conveyed to the physician, and the response to this advice. Assays performed by a multidisciplinary therapeutic drug monitoring (TDM) service during a 1-month period in 1988 and again in 1992 were chosen for review. Theophylline concentration in plasma was quantified by fluorescence polarization immunoassay. Medical technologists interpreted results and made specific recommendations concerning dose changes and/or need for follow-up assays on 48.5 (1988 survey) and 37.9% (1992 survey) of results. Review of these recommendations revealed that only ∼1% could have been improved or were incorrect. Physician compliance with dose change recommendations was similar in both surveys (X2= 0.16,p= 0.7), with recommendations being followed on 75.9(1988) and 73.3% (1992) of occasions. Compliance with recommendations for ordering additional samples at specific times also was similar between the two surveys (X2= 2.06,p= 0.15), with recommendations being followed on 75 (1988) and 87.2% (1992) of occasions. Overall, combining the data for both surveys, (a) significantly more out-patients than in-patients (69.2 versus 27.8%, respectively) were subtherapeutic, (b) significantly fewer out-patients than in-patients (27.6 versus 70.2%, respectively) were within the therapeutic range (X2= 33.7,p< 0.001), but (c) numbers (2–4%) of potentially toxic results within the two groups were similar.

ISSN:0163-4356    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Using an in vitro pharmacokinetic model, area under the curve (AUC) estimates from an osmotic continuous-withdrawal device were compared to AUC estimates by a conventional trapezoidal method. Ten experiments were done under two different conditions: (a) half-life of 1 h (n= 5) and (b) half-life of 2 h (n= 5). Sampling was done for 6 and 12 h, respectively. The AUC estimates from the two methods were highly correlated (r= 0.948,p< 0.0001). The mean coefficient of variation was 9.5% (n= 10), and mean AUC values were not statistically different by analysis of variance (p= 0.4). The sampling device sampled at 0.121 ± 0.011 ml/h; the mean volume was 0.79 ± 0.03 and 1.34 ± 0.02 ml over 6 and 12 h, respectively. Continuous sampling provided a reasonable estimation of AUC, required only one analytical sample, and sampled at a consistent zero-order rate.

ISSN:0163-4356    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

To establish the usefulness of fluorescence detection to quantify urinary concentrations of dextromethorphan and dextrorphan for oxidation phenotyping, we determined the molar concentration ratio of dextromethorphan to dextrorphan in 38 subjects by UV and fluorescence detection. Dextromethorphan and dextrorphan concentrations were quantified after overnight hydrolysis of urine samples and organic solvent extraction with heptane and butanol. The compounds were separated by high-performance liquid chromatography using a phenyl column and a mobile phase consisting of acetonitrile and an aqueous mixture of 0.01Mheptane sulfonic acid and 0.01Mphosphate buffer. The eluents were detected in series by a UV detector (280 nm) and fluorescence detector (excitation 280 nm and emission 310 nm). The dextromethorphan to dextrorphan molar concentration ratio by UV and fluorescence detection was highly correlated (r= 0.997) and not statistically different (p= 0.1036). However, increased sensitivity with fluorescence detection enabled detection of lower dextromethorphan and dextrorphan concentrations when compared with UV detection. Fluorescence detection was able to detect dextromethorphan as low as 0.02 μg/ml, which may be helpful in phenotyping individuals with extremely rapid metabolism of dextromethorphan. Fluorescence detection also produced chromatograms with significantly less interference and allows a more accurate quantitation of dextromethorphan and dextrorphan concentrations.

ISSN:0163-4356    

出版商:OVID    

年代:1993

数据来源: OVID

ISSN:0163-4356    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

An expedient and specific liquid chromatographic method for a concurrent measurement of fluoxetine (FLU), norfluoxetine (NFLU), amitriptyline (AMI), nortriptyline (NTRIP), imipramine (IMI), and desipramine (DES) is described. Using a mixture of acetonitrile:methanol:0.056Mammonium acetate:1Mammonium hydroxide (100:10:4.5:2.6, by volume) as mobile phase, the compounds along with doxepin (DOX) (internal standard) were separated on a 10 μ, 8 mm x 10 cm C18Resolve cartridge in conjunction with radial compression liquid chromatographic module, and were detected in the effluent spectrophotometrically at 220 nm. A hexane:isoamyl alcohol (98:2, by volume) solution was used for extraction of plasma and the drugs were removed from the organic phase with 0.03% phosphoric acid prior to injection. Under these conditions, no interference in the assay was observed, and the retention times of NFLU, DOX, FLU, AMI, IMI, NTRIP, and DES were 7.8, 11.6, 16, 17.8, 20.9, 31, and 35 min, respectively. The assay was highly linear (r > 0.994), and the within- and between-day coefficient of variance was consistently ≥9.8%. This assay is currently being used to simultaneously measure these drugs in patients and to investigate their steady-state pharmacokinetics when used in combination.

ISSN:0163-4356    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The determination of antiepileptic drugs in human serum by micellar electrokinetic capillary chromatography (MECC) with direct sample injection is discussed. Nanoliter quantities of patient sera are applied to the beginning of a fused silica capillary filled with a phosphate/borate buffer (pH 9.2) containing 75 mMsodium dodecylsulfate. Upon application of an electric field along the capillary, endogenous and drug substances are transported toward the cathode and separate into distinct zones which are detected by on-column UV absorption. Phenobarbital, ethosuximide, and primidone are shown to elute in front of the solubilized proteins, thus permitting quantitation of these drugs without any sample pretreatment. For phenobarbital and ethosuximide, MECC data obtained using the external standard method and peak areas as the basis for quantitation are shown to be in excellent agreement with those of nonisotopic immunoassays and, for ethosuximide, also with those of high-performance liquid chromatography. The correlation coefficients (n = 50) are between 0.972 and 0.986. Intraday and interday reproducibility data are 2.0–4.5% and 4.5–8.0%, respectively. For primidone, insufficient samples have been available for a comprehensive comparison of MECC data with those of other analytic techniques.

ISSN:0163-4356    

出版商:OVID    

年代:1993

数据来源: OVID