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11. |
Heparin Pharmacokinetics During Hemodialysis |
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Therapeutic Drug Monitoring,
Volume 11,
Issue 6,
1989,
Page 674-679
Robert Kandrotas,
Peter Gal,
Jean Douglas,
James Deterding,
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摘要:
The disposition of heparin was studied in 21 chronic hemodialysis patients. Heparin was administered as a bolus injection in doses of 3,000–12,000 U. Combined zero and first-order elimination was demonstrated, with heparin half-life declining by 74% over 3.5 h during dialysis. Assumption of a first-order pharmacokinetic model of elimination resulted in a mean difference of 0.001 U/ml between actual and predicted heparin concentrations. Mean first-order pharmacokinetic parameters were: half-life, 117 min; heparin volume of distribution (V), 68 ml/kg; clearance, 28 ml/min. A high degree of interpatient variability was also observed. A comparison ofVand plasma volume (PV) revealedVto be significantly greater thanPV(p< 0.001), indicating distribution outside the plasma compartment. When compared to blood volume, there was no significant difference (p > 0.1), indicating that blood volume may be used to approximateV. The nonlinear component of the elimination process is not clinically significant within the range of therapeutic plasma concentrations used during hemodialysis, but the high degree of interpatient variability indicates that dosage individualization may be useful.
ISSN:0163-4356
出版商:OVID
年代:1989
数据来源: OVID
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12. |
Digoxin Elimination in a Functionally Anephric Patient After Digoxin‐Specific Fab Fragment Therapy |
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Therapeutic Drug Monitoring,
Volume 11,
Issue 6,
1989,
Page 680-685
Naziha Nuwayhid,
George Johnson,
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摘要:
The elimination of total digoxin after digoxin-specific Fab fragment therapy in a patient in end-stage renal disease is described. Two-component, nonlinear exponential regression of the patient's total digoxin concentration data revealed biphasic elimination: a fast phase with a half-life of 43 h and a slow phase with a half-life of 330 h. Serum total digoxin concentration decreased 20% 12 h after the initiation of Fab fragment therapy. The mean serum concentrations of total digoxin and apparent total digoxin as measured by fluorescence polarization immunoassay during a 520-h period after the initiation of therapy were 18.42 and 14.77 ng/ml, respectively (n = 15). The correlation between the two measurements was good (r= 0.987). The time course of free digoxin concentration obtained after ultrafiltration at 2, 20, or 37dGC is also described. The free digoxin concentrations (n = 10) at these temperatures averaged over a 282-h period were 0.35, 0.53, and 0.82 ng/ml, respectively (p< 0.001, 2dGC vs. 37dGC).
ISSN:0163-4356
出版商:OVID
年代:1989
数据来源: OVID
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13. |
Human Scalp Hair as Evidence of Individual Dosage History of HaloperidolProspective Study |
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Therapeutic Drug Monitoring,
Volume 11,
Issue 6,
1989,
Page 686-691
Reiko Sato,
Toshihiko Uematsu,
Ryuichi Sato,
Shin Yamaguchi,
Mitsuyoshi Nakashima,
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摘要:
The concentration of haloperidol in hair was measured by radioimmunoassay after hairs were dissolved in 2.5 N NaOH solution and the drug was extracted. In patients to whom haloperidol had been administered at fixed daily doses for more than 1 month, and in whom therapy had been just discontinued (group A, n = 5) or the doses cut to half (group B, n = 3), hairs were collected when the dose was changed and at 1 and 2 or 3 months thereafter. A few strands of hair collected on each occasion were cut into 1-cm-long portions from the roots, and the haloperidol concentration was measured in each portion. When hairs were assumed to grow at a rate of 1–1.5 cm/month, the portion of hair that reflected the change of dose was observed to move upward along the hair length in all patients of group A. However, these phenomena were less obvious in group B. These results indicate that at the least, hair could serve as an indicator of individual exposure or nonexposure to haloperidol and could yield retrospective information. In rats whose hairs had been removed by plucking from an area on the back, either saline or 1 mg/kg of haloperidol (i.p., b.i.d.) was administered for 2 weeks (first period), followed by 0, 0.5, 1, or 2 mg/kg b.i.d. for the subsequent 2 weeks (second period). At the end of each period, hairs that had grown in the plucked area were collected. Within-groups, haloperidol levels in hairs collected at the end of each period corresponded to the doses given. The distribution of drug levels in the upper and lower halves of hairs collected only at the end of the second period corresponded in general to the doses given. These results support the potential usefulness of hair in therapeutic drug monitoring.
ISSN:0163-4356
出版商:OVID
年代:1989
数据来源: OVID
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14. |
The Use of Aerosolized Tobramycin in the Treatment of a Resistant Pseudomonal Pneumonitis |
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Therapeutic Drug Monitoring,
Volume 11,
Issue 6,
1989,
Page 692-695
Charles McCall,
William Spruill,
William Wade,
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摘要:
Aerosolized tobramycin was given to a 68-year-old man with resistantPseudomonas aeruginosapneumonitis at a dose of 100 mg every 8 h via a tracheostomy, after the patient failed to respond adequately to parenteral aminoglycoside and ticarcillin therapy. Minimum inhibitory concentration and minimum bactericidal concentration for tobramycin and gentamicin were 16 mUg/ml and >16 mUg/ml, which necessitated aerosol administration. Tracheal concentrations 15 min and 4 h after a dose were 1,560 and 930 mUg/ml. The patient responded and eventually was discharged from the hospital. Thus, monotherapy with an aerosolized aminoglycoside may be effective in some patients with resistantPseudomonas aeruginosapneumonitis.
ISSN:0163-4356
出版商:OVID
年代:1989
数据来源: OVID
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15. |
A Radioreceptor Assay for the Measurement of Cyclosporine ActivityA Preliminary Report |
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Therapeutic Drug Monitoring,
Volume 11,
Issue 6,
1989,
Page 696-700
James Donnelly,
Steven Soldin,
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摘要:
Cyclosporine A (CsA) is extensively metabolized in the liver. Some of the known metabolites share immunosuppressive properties with the parent drug. Furthermore, CsA therapy is used in an increasing number of clinical conditions, some of which affect the pharmacokinetics of the drug. At this time, it is not yet known if CsA or its metabolites are responsible for the nephrotoxicity or hepatotoxicity observed in some individuals. Some high-performance liquid chromatography (HPLC) and monoclonal immunoassay procedures measure parent drug and not the pharmacologically active metabolites, while polyclonal immunoassays and nonspecific monoclonal antibody immunoassays measure both parent drug and metabolites. However, it is unlikely that the degree of cross-reactivity with metabolites correlates with their immunosuppressive effect. To overcome these drawbacks, we have developed a method of measuring CsA activity in whole bloods using specific receptors from the cytosol of human mononuclear leukocytes that have been semipurified through ultracentrifugation. The basis of the procedure is the competitive binding at specific receptor(s) between a constant concentration of [3H]dihydrocyclosporine and the variable concentrations of cyclosporine and its pharmacologically active metabolites in whole blood. Comparisons between six different assays (three specific, two nonspecific, and the receptor assay) were made. Overall, the two specific radioimmunoassay procedures correlated well to HPLC, while correlation of the two nonspecific immunoassay procedures to HPLC was poor. Poor correlation was also found to exist between the radioreceptor assay and the nonspecific assays, indicating that the cytosolic binding of CsA and its metabolites cannot be correlated to currently available assays.
ISSN:0163-4356
出版商:OVID
年代:1989
数据来源: OVID
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16. |
An Improved Sensitive Assay for Simultaneous Determination of Plasma Haloperidol and Reduced Haloperidol Levels by Liquid Chromatography Using a Coulometric Detector |
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Therapeutic Drug Monitoring,
Volume 11,
Issue 6,
1989,
Page 701-707
M. Hariharan,
Erick Kindt,
Ted VanNoord,
Rajiv Tandon,
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摘要:
A simple, highly sensitive and specific high-performance liquid chromatographic method that uses a coulometric detector for the simultaneous assay of haloperidol and reduced haloperidol in human plasma has been developed, using bromoperidol as the internal standard. A reversed phase C85-mUm column (25 x 0.46 cm) and a mobile phase of phosphate buffer (pH 7.0), acetonitrile, and methanol (40:20:40 vol/vol) are used for separating the analytes. The analytes are extracted from alkalinized plasma using a mixture of pentane and isopropanol (95:5 vol/vol) and purified by back extraction into a perchloric acid solution. Teflon tubes with screw caps are used throughout the extraction work. The compounds are oxidized at a potential of + 0.90 V against a Ag/AgCl reference electrode. The detection limit of the assay is 50 ng/L using 1 mL of plasma. The average interassay coefficient of variation for samples of concentration 1–40 mUg/L is 8%. Possible drug interferences in the assay have been studied. The absolute recovery of the method is 80%. The assay has been validated by quantitating 150 schizophrenic patients' samples.
ISSN:0163-4356
出版商:OVID
年代:1989
数据来源: OVID
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17. |
High‐Performance Liquid Chromatographic Assay of Flecainide and Its Enantiomers in Serum |
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Therapeutic Drug Monitoring,
Volume 11,
Issue 6,
1989,
Page 708-711
L. Lie-A-Huen,
R. Stuurman,
F. Ijdenberg,
J. Kingma,
D. Meijer,
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摘要:
Two analytical methods are described for the determination of flecainide in serum by high-performance liquid chromatography employing spectrofluorimetric detection. One method concerns total flecainide, whereas the other covers the assay of flecainide enantiomers separately. The stereo-specific assay is based on a precolumn derivatization of flecainide enantiomers to urea derivatives with the chiral compound R-( + )-1 phenyl-ethyl-iso-cyanate. By formation of the permanent diastereomers, the racemic mixture can be resolved with a traditional reversed-phase column. The run time of the total flecainide assay is 15 min, whereas that of its enantiomers is 20 min. The extraction recovery from serum in both methods is 85%. The intraassay precision of the nonstereospecific assay in serum ranged from 99 \pm 3% (coefficient of variation) to 101 \pm 5%. The accuracy of the estimation in serum ranged from 100 to 103%. The intraassay precision of the stereospecific assay in serum ranged from 98 \pm 5% (coefficient of variation) to 103 \pm 7%. The accuracy of the estimation in serum ranged from 101 to 104%. The limit of quantitation was 0.05 mg/L for both methods.
ISSN:0163-4356
出版商:OVID
年代:1989
数据来源: OVID
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18. |
Reactivity Considerations in the Analysis of Glucuronide and Sulfate Conjugates of Diflunisal |
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Therapeutic Drug Monitoring,
Volume 11,
Issue 6,
1989,
Page 712-720
Ronald Dickinson,
Andrew King,
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摘要:
Reactivity of glucuronide and sulfate conjugates was taken into account in development of a simple isocratic HPLC method for direct assay of diflunisal (DF) and its acyl glucuronide (DAG), phenolic glucuronide (DPG), and sulfate (DS) conjugates. Whereas DPG was stable over the pH range 0–9, DAG was highly labile at neutral to slightly alkaline pH, undergoing rearrangement (isomerisation via acyl migration), hydrolysis, and, in the presence of methanol, transesterification to DF methyl ester. The 2-, 3-, and 4-O-acyl positional isomers of DAG appeared as three pairs of peaks. Interconversion between partners of each pair occurred even under acidic conditions inhibitory to acyl migration, implicating mutarotation. DS was stable at neutral to slightly alkaline pH, but underwent hydrolysis under relatively strongly acidic conditions. However, this hydrolysis was remarkably catalyzed (e.g., by 1,000-fold) in the presence of solvents (i.e., solvolysis) such as diethyl ether and ethyl acetate. DS (an acid) could not be extracted from aqueous solution because of this acidic solvolysis. Suitable conditions for simultaneous direct analysis (nonextractive, nonconcentrative) of DF and its reactive (DAG and DS) and unreactive (DPG) conjugates were achieved by working at pH of approximately 4.5. The procedure thus developed is suitable for plasma, urine, and bile samples, and has revealed the presence of new, as yet unidentified, metabolites of DF.
ISSN:0163-4356
出版商:OVID
年代:1989
数据来源: OVID
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19. |
Diazepam Treatment Does Not Influence the Debrisoquine or Mephenytoin Hydroxylation Phenotyping Tests |
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Therapeutic Drug Monitoring,
Volume 11,
Issue 6,
1989,
Page 721-723
Eduardo Spina,
Anna Buemi,
DREmilio Sanz,
DRLeif Bertilsson,
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摘要:
Debrisoquine and S-mephenytoin hydroxylation phenotyping tests were performed in 9 patients before and during treatment with diazepam at a daily dose of 10 or 15 mg. There was no change in either the debrisoquine/ 4-hydroxydebrisoquine ratio or the ratio of S/R mephenytoin in urine. The hydroxylation of these two test drugs is apparently not inhibited by administration of therapeutic doses of diazepam.
ISSN:0163-4356
出版商:OVID
年代:1989
数据来源: OVID
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20. |
Interference from a Red Top Venojet Tube in High‐Performance Liquid Chromatographic Analyses |
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Therapeutic Drug Monitoring,
Volume 11,
Issue 6,
1989,
Page 724-724
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PDF (108KB)
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ISSN:0163-4356
出版商:OVID
年代:1989
数据来源: OVID
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