摘要:

In a crossover study balanced for sex, treatments, and treatment order, we have investigated the pharmacokinetics of diltiazem after single oral doses in 10 healthy middle-aged volunteers. The diltiazem doses employed were 60 mg and 120 mg and contained 1.85 MBq [14C] diltiazem. The absorption was rapid and did not differ between treatments. The disposition could be described using a two-compartment model with terminal half-lives of 5.68 \pm 2.62 h (mean \pm SD) after 60 mg and 5.5 \pm 2.22 h after 120 mg. The half-life of the metaboliteN-demethyldiltiazem (MA) was similar to or slightly longer than that of diltiazem, whereas the half-life of deacetyldiltiazem (M1) was longer: 9.80 \pm 5.27 h and 10.43 \pm 5.38 h (n = 5). The area under the curve (AUC) of diltiazem increased significantly more than twofold after doubling of the dose, indicating an increased bioavailability, probably because of decreased presystemic elimination. The ratio between the AUCs for metabolites and diltiazem were 0.48 \pm 0.12 and 0.45 \pm 0.06 for MAand 0.16 \pm 0.10 and 0.15 \pm 0.10 for M1after 60 mg and 120 mg diltiazem. The cumulative excretions of radioactivity within 120 h were 86 \pm 9% and 87 \pm 6%. The tracer was mainly excreted in urine (69 \pm 7% and 72 \pm 6%) and the remaining amounts were excreted in feces.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The pharmacokinetics of diltiazem in healthy middle-aged volunteers have been investigated after single and multiple doses. Twenty men or women were recruited and were given one single dose and one steady-state treatment in a crossover fashion. Ten were given 60-mg single dose and 60-mg t.i.d. during 14 days and 10 received 120 mg as a single dose and as 120-mg t.i.d. The single dose and the last dose in steady state were pulsed with 1.85 MBq [14C]diltiazem. The absorption was rapid and did not differ between treatments. The disposition could be described using a two-compartment model with terminal half-lives of 6.27 \pm 3.23 h (mean \pm SD) after a single dose of 60mg diltiazem, 6.05 \pm 1.59 h after 60-mg diltiazem t.i.d., 5.85 \pm 1.04hafter 120-mg diltiazem and 5.90 \pm 0.69 h after 120-mg diltiazem t.i.d. The half-life of the metaboliteN-demethyldiltiazem was similar to that of diltiazem whereas the half-lives of the metabolites deacetyldiltiazem andN-demethyldeacetyl-diltiazem were longer. The area under the curve of diltiazem in a dosing interval at steady state increased significantly compared with the single dose, indicating an increased bioavailability after repeated dosing, probably because of decreased presystemic elimination. The cumulative excretions of radioactivity in urine within 120 h were 72 \pm 5%, 71 \pm 8%, 71 \pm 6%, and 73 \pm 4%, respectively. The remaining amounts were excreted in feces.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The elimination half-life and plasma concentrations of bupivacaine were predicted after its epidural administration in six pregnant women at term for elective Caesarean section using a repeated one-point method. There was a direct correlation between predicted concentrations and observed concentrations of bupivacaine using this simple method (r= 0.9947). The assay of bupivacaine in a 0.5-ml plasma by gas chromatography with nitrogen sensitive detection can be achieved in a short time (rapid extraction and chromatographic analysis required 20 min and 10 min, respectively) to cope with emergency. It is suggested that the repeated one-point method may be useful to obtain early prediction of kinetic parameters in patients who required prolonged epidural anesthesia with bupivacaine in order to minimize adverse effects.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Digoxin therapy can cause important toxic events when elevated drug levels occur. Interpreting drug levels can be hampered by artifactual errors such as poor assay quality, incorrect timing or drawing of blood samples, and, as has been demonstrated for tobramycin, errors due to drawing blood through drug administration catheters. A case is reported in which a correctly timed and analyzed digoxin level of 33.60 ng/ml may have been due to drawing the blood sample through a line used to administer digoxin eight hours earlier. Subsequent measurements by venipuncture documented much lower concentrations.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The aminoglycoside antibiotics are useful in the treatment of gramnegative bacillary infections but are potentially toxic. A method to maximize their therapeutic benefit while minimizing their risk of toxicity is desirable. Serial pharmacokinetic dosing has been proposed as a method to achieve these goals. An audit was conducted comparing optimal dosing of aminoglycosides by physicians of a community hospital using a serial pharmacokinetic dosing service versus its nonuse. Optimal dosing was 81% (81/101) of trough-peak pairs using the service versus 17% (28/161) not using the service (p< 0.001). This difference was due to greater achievement of therapeutic peak levels with the service (96%, 97/101) than without (32%, 52/161). There was no difference in toxic trough level occurrence, with 15% (15/101) occurrence with the service and 17% (27/161) occurrence without its use (p> 0.05). Clinical nephrotoxicity occurred 0% (0/49) of the time with the use of the service versus 7% (6/88) of the time without its use (p> 0.05). The data presented here demonstrate that serial pharmacokinetic dosing of aminoglycosides results in the achievement of therapeutic peak levels in most patients. An understanding of aminoglycoside nephrotoxicity and pharmacokinetics allows the subsequent adjustment of dosing, if necessary, to avoid nephrotoxicity in most patients.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

During the development of a homogeneous immunoassay for the antibiotic vancomycin, we observed in certain patient samples a quantitation difference between the enzyme multiplied immunoassay technique (EMIT) method and the comparison method, fluorescence polarization immunoassay (FPIA). This prompted us to evaluate the integrity of vancomycin in samples from renally impaired patients. Since it has been reported in the scientific literature that vancomycin degrades into an antibiotically inactive crystalline degradation product (CDP-1) in vitro, we developed high-performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometry (LC/MS) methods to determine whether CDP-1 is present in patient sera. HPLC and LC/MS analysis on samples from renally impaired patients positively identified CDP-1 in fresh samples. Next, we tested the cross-reactivity of three currently available vancomycin immunoassays, radioimmunoassay (RIA) FPIA, and EMIT, to CDP-1 prepared in our laboratory. Our data suggest that CDP-1 is recognized by FPIA and RIA, both polyclonal antibody-based methods, but not by EMIT, which uses a monoclonal antibody.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Cyclosporine (CsA) through blood concentrations were determined by polyclonal nonspecific radioimmunoassay (RIA) (Sandoz), monoclonal specific and nonspecific RIA (Sandimmun, Sandoz), monoclonal specific and polyclonal nonspecific RIA, (Cyclo-Trac, INCSTAR) and fluorescence polarization immunoassay (TDx, Abbott), at multiple points in time, in two patients receiving CsA for immunosuppression after heart transplantation. Results obtained by the different nonspecific methods have a correlation (r) from 0.76 to 0.94. Concentrations determined by Sandimmun nonspecific RIA, CycloTrac nonspecific RIA and TDx were consistently higher than those by Sandoz nonspecific RIA, owing to different cross-reactivity with CsA metabolites, giving ratios of 1:8, 1:4, and 1:6, respectively. In the first patient, the ratios between nonspecific and specific results were higher during days 1–20 than later on, which coincides with the high serum bilirubin level observed (r= 0.72, n = 31). This observation was not made in the second patient, whose liver function was within normal limits. Because CsA and its metabolites are eliminated primarily in the bile, the high values obtained with the nonspecific assay indicate that CsA metabolites accumulate in blood when liver function is impaired.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Ways of improving sensitivity of the radioreceptor assay to determine the plasma levels of dihydropyridine calcium antagonists were investigated. Extraction of the drug from plasma with organic solvent was found to enhance the sensitivity of the assay (method 1). Alternatively, the inhibitory effect observed when plasma is added directly to the binding assay can be counteracted by increasing the amount of membranes in the assay (method 2). Plasma levels after single oral doses of nitrendipine and nicardipine were followed with method 1. Plasma levels of isradipine were measured with methods 1 and 2 and by mass fragmentography. The data confirm that nitrendipine plasma level kinetics vary widely from patient to patient, whereas for nicardipine the drug level profile is more homogeneous. The similarity of the data obtained from the radioreceptor assay and from mass fragmentography suggests the absence of any active metabolite of isradipine.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

This paper describes the synthesis of amphetamine derivatives, functionalised at the para-position of the phenyl ring of the drug. These derivatives were used to prepare fluorescein-labelled amphetamine to replace the label in a previously described polarisation fluoroimmunoassay that is highly specific for amphetamine. The original label was obtained using material donated by industrial sources and therefore not generally available. When the new label was used in the immunoassay, specificity was similar but the sensitivity was improved by a factor of four. This increase in sensitivity is explained by elimination of bridge-binding effects.

ISSN:0163-4356    

出版商:OVID    

年代:1989

数据来源: OVID