ISSN:0163-4356    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

Determination of serum concentrations of certain drugs is becoming increasingly important for optimal patient care. These drugs include many antibiotics, several antiarrhythmics, cardiac glycosides, lithium, phenytoin, some other anticonvulsants, salicylates, and theophylline. Serum level determinations can also be useful for establishing the best individual dosage of benzodiazepines, phenothiazines, and tricyclic antidepressants. On the other hand, information about serum levels is not necessary or useful for many widely used drugs. In general, measurement of serum concentrations is valuable only for drugs whose dosage should be individualized and whose therapeutic and toxic actions are not adequately quantifiable by clinical endpoints. The serum concentration of the drug and of important active metabolites must be accurately measurable, the relation between their concentrations in the serum and the intensity of therapeutic and toxic effects during clinical use must have been clearly defined, and serum levels must always be knowledgeably interpreted in conjunction with careful clinical observation and judgment. Measurements of serum drug concentrations are most often useful during prophylactic drug therapy, in patients with major pharmacokinetic disturbances, and when patients show unusual and unexplained sensitivity or resistance to therapy with a drug.

ISSN:0163-4356    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

Serum level monitoring of antiepileptic drugs is important for an optimal drug therapy since relationships between serum levels and therapeutic and toxic effects have been clearly established for several drugs. Routine serum level monitoring based on pharmacokinetic and clinical knowledge has improved the treatment of epileptic patients.For routine determination of antiepileptic drugs, homogenous enzyme immunoassays offer several advantages over more complex techniques such as GLC and HPLC. Because of the speed of the analysis and the small sample volume, EMIT® is the method of choice in many laboratories. A 50-μl sample is sufficient for a single determination of up to five drugs. To ensure reliable results, quality control schemes are necessary regardless of the analytical technique utilized for drug quantitation. Routine monitoring of serum levels is especially important since drug bioavailability, as well as the rate of drug metabolism and excretion, varies widely among patients. Serum levels are also influenced by comedication. Changes in protein binding may also be of clinical importance under special circumstances. Active metabolites may contribute to the clinical effect of a drug. Correct dose frequency and standardized blood sampling time, preferably before the first morning drug dose, are also important factors for establishing optimal therapeutic regimens for a given patient. The serum levels of antiepileptic drugs should be determined when drug therapy is initiated, after dosage adjustments, in case of therapy failure, after addition of drugs which may cause drug interactions, when clinical signs of side effects or drug intoxication occur, and as a routine monitoring for patient compliance. Serum levels should be monitored if any change occurs in a patient's normal pharmacological state.

ISSN:0163-4356    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

The pharmacokinetics and bioavailability of mephobarbital have been studied in 2 volunteers. Plasma levels of mephobarbital and phenobarbital were measured by gas chromatography-mass spectroscopy with selected ion monitoring. Urinary output of phenobarbital and thep-hydroxy derivatives of both mephobarbital and phenobarbital was measured by high pressure liquid chromatography. The time course of these plasma and urinary levels was monitored following single 800-mg oral and 200-mg intravenous doses in the 2 patients. The major conclusions of the study were that mephobarbital is reasonably well absorbed following oral dosing and that some 35% or so of the dose (by either route) is converted to the recently identified metabolite,p-hydroxymephobarbital.

ISSN:0163-4356    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

A reversed-phase liquid chromatographic procedure was developed for simultaneous quantitation of three metabolites of the anticonvulsant methylphenobarbital in urine. These werep-hydroxyphenobarbital, phenobarbital, andp-hydroxymethylphenobarbital. Enzymatic hydrolysis was employed for liberation of the phenolic barbiturates from their glucuronide conjugates. Two internal standards were used at widely different concentrations, which conferred on the assay an accuracy over a wide concentration range. Concentration and instrument response (ultraviolet absorption at 215 nm) were linearly related over the concentration ranges of interest. The within-batch and between-day coefficients of variation were less than 4% in all cases. Recovery of all three analytes from the urine was nearly complete, and no substances that interfered with the assay were encountered in clinical specimens.

ISSN:0163-4356    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

It is generally agreed that the bronchodilator response to theophylline can be directly related to plasma concentration and that the efficacy of theophylline therapy can be improved if plasma concentrations are monitored. However, it is not known whether this improvement is realised in routine clinical practice. In this study, theophylline plasma concentrations were measured in 359 outpatients attending a teaching hospital respiratory medicine clinic. In nearly three-quarters of these patients (73.2%), the plasma concentration of theophylline was below the recommended therapeutic range of 55–110 μmoles/liter (10–20 mg/liter). These results were made available to the medical staff at the patient consultation. One hundred and seventy-seven patients reattended for a second visit and their plasma concentrations remeasured. At this visit, 63.2% of plasma levels were below the therapeutic range of 55–110 μmoles/liter; the percentage of patients in this therapeutic range had risen from 25.6% at the first visit to 33.9% at the second. Concentrations in excess of 110 μmoles/liter were rare and accounted for only 1.1–2.8% of samples assayed. The increase in the percentage of patients whose plasma concentration was in the therapeutic range may have been due to a better patient compliance resulting from provision of the “on-line” plasma monitoring service. The data suggest that physicians are conservative in their use of theophylline and may be maintaining the patients at a therapeutic range of 28–55 μmoles/liter, particularly when the drug is given with other therapeutic agents such as the β2-adrenoceptor agonists.

ISSN:0163-4356    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

The large interpatient variability in gentamicin half-life and distribution volume in children and the lack of accurate methods of predicting these parameters necessitate individualization of doses based on measured serum concentrations. For practical reasons, a predose nadir and postdose peak (obtained before and after the same dose) have been used to make dose adjustments. To assess the accuracy of this approach, pharmacokinetic parameters estimated from pre- and postdose concentrations measured in 21 children were used to adjust doses and simulate new steady-state peak and nadir concentrations. A total of 53 dose adjustments was evaluated in these 21 patients. The accuracy of this method was compared to results obtained in a control group of 40 children who had steady-state serum concentrations simulated from kinetic parameters calculated from three serial serum concentrations (0.5, 3, and 6 hr after a dose). A one-compartment kinetic model was used for all dosage calculations and for simulation of serum concentrations at the new dosages. All patients in both groups were between 2 and 15 years of age, had stable normal renal function, and were being treated for bacterial infections. The accuracy of both methods was assessed by comparing concentrations predicted for the new dosage to concentrations measured at steady state. The line of best fit for the rectilinear plot of measured (x) versus predicted (y) gentamicin serum concentrations for the control group was described by the equation:y= 0.922x+ 0.23,r= 0.901. The same data for the study group were described by the equation:y= 0.873x+ 0.59,r= 0.813. Simultaneous testing of the slopes and intercepts (jointF-test) indicated that neither of these lines was significantly different from the line of reference. These data show that the use of predose nadir and postdose peak serum concentrations to make dose adjustments results in significantly greater error than using three serial samples (r2= 0.66 vs. 0.81,p< 0.02). Although the error with the former method is comparable to that encountered with nomograms and equations commonly used to estimate gentamicin kinetic parameters in adults, and offers an alternative in children, this method is only recommended as an adjunct with more traditional pharmacokinetic approaches to individualizing therapy.

ISSN:0163-4356    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

Simultaneous steady-state plasma concentrations of carbamazepine and carbamazepine-10, 11-epoxide were measured by high performance liquid chromatography in 295 patients. Plasma carbamazepine epoxide correlated more closely with carbamazepine dose than did plasma levels of the drug itself. Plasma carbamazepine epoxide levels tended to be higher, relative to drug dose, in children than in adults, whereas age did not seem to influence the relationship between plasma carbamazepine level and drug dose. Simultaneous phenytoin intake lowered the plasma carbamazepine levels relative to drug dose but left plasma carbamazepine epoxide levels largely unaltered. However, simultaneous valproate intake was associated with raised plasma carbamazepine epoxide levels relative to carbamazepine dose, whereas plasma carbamazepine levels were unaltered. The amount of conversion of carbamazepine to its epoxide thus appears to vary in different circumstances in humans.

ISSN:0163-4356    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

The pharmacokinetics of intravenously administered cefotaxime were studied in 11 patients with creatinine clearances of less than 7 ml/min who were undergoing chronic hemodialysis. Eight were studied during dialysis, and 3 were studied between dialyses. Pharmacokinetic parameters were determined using a two-compartment linear model. The serum half-life of cefotaxime off dialysis ranged from 1.48 to 3.78 hr. The half-life during dialysis was 2.52 \pm 0.34 hr. There was a 28% reduction in serum concentration per hour. A dosage schedule for the use of intravenously administered cefotaxime in patients undergoing hemodialysis is presented.

ISSN:0163-4356    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

The effect of Mylanta® on naproxen bioavailability was studied in 11 healthy volunteers. In separate experiments, single oral doses of naproxen (250 mg) and multiple oral doses (250 mg twice daily for 7 days) were administered with and without Mylanta. Coadministration of naproxen with Mylanta in the single-dose experiment did not significantly affect the area under the curve (579 vs. 580 μg/ml x hr with and without Mylanta, respectively), time to peak serum concentration (2.5 vs. 2.6 hr), peak serum concentration (37.2 vs. 34.8 μg/ml) or plasma half-life (16.1 vs. 16.4 hr). There was no significant difference between trough level naproxen concentrations at steady state (29.6 μg/ml with Mylanta vs. 30.7 μg/ml without Mylanta). The data were also used to investigate naproxen pharmacokinetics predicted by two different pharmacokinetic models, one of which allowed for protein binding. The nonlinear protein-binding model accurately predicted steady-state concentration, while the values predicted by the linear model exceeded actual values by 33–54%.

ISSN:0163-4356    

出版商:OVID    

年代:1981

数据来源: OVID