ISSN:0163-4356    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Urinary samples were collected from individuals not taking cardiac glycosides. Aliquots of 30 ml were passed through preparative octadecylsilane-bonded phase columns and eluted in fractions by stepwise increasing concentrations of acetonitrile. Eluted fractions were analysed for their contents of endogenous digoxinlike substance (EDLS) by radioimmunoassay of digoxin and by a bioassay of cardiac glycosides, which measures the uptake of rubidium (86Rb) by erythrocytes as an index of Na+, K+-ATPase activity. In both assays, digoxinlike activity was found in several fractions, but the highest values were consistently measured in the fractions eluted with 40% acetonitrile. Greater amounts of EDLS were recovered from the urine of pregnant women than from the urine of men and nonpregnant women.

ISSN:0163-4356    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Cyciosporin A (CyA) undergoes saturable binding to erythrocytes. Theoretically, measurement of erythrocyte concentration can be used to estimate the unbound concentration, which in turn may be more closely related to response than total plasma concentration. This possibility for estimating unbound concentration was explored in 139 blood samples taken from renal transplant patients who received CyA therapy. In practice, the method proved to be no better than that obtained by assuming a constant fraction CyA in plasma unbound. In this study, however, both methods were too imprecise to be of practical value. If unbound CyA concentration is to be determined it must be measured directly or must be estimated by multiplying total plasma concentration by fraction of drug unbound.

ISSN:0163-4356    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

The usefulness of therapeutic monitoring for cyclosporin in transplant patients is still open to question due to variability of the data. One source of variability, the binding within plasma, was examined in renal transplant patients undergoing cyclosporin therapy. The fraction unbound varied between 0.04 and 0.13. A model based on physiochemical principles, involving concurrent partition of the drug between water, cholesterol, and triglyceride, was used to account for the variation in binding. Simulations using this model indicate that plasma cholesterol is a major factor contributing to the variability in fraction unbound and that the effect of triglyceride is less by a factor of four.

ISSN:0163-4356    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

The relationship between blood cells and plasma concentrations of cyclosporin A (Cy A) determined by radioimmunoassay, was investigated in 12 heart and 12 kidney transplant recipients. The decision between a linear and nonlinear model was made according to a standardized residuals plot. We observed high blood cells-plasma concentration ratios in the two groups, indicating a high affinity of Cy A for blood cells. The distribution of Cy A between blood cells and plasma was ascribed to a nonlinear saturable model in the two groups. According to our results we have simulated the blood-plasma concentration ratio of Cy A as a function of plasma Cy A concentration and he-matocrit.

ISSN:0163-4356    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Verapamil has been shown to be effective in reducing the frequency of episodes of ischemic pain in patients with unstable angina pectoris, and to be more effective than β-adrenoceptor antagonists in such patients. However, in many patients ischemic symptoms persist despite verapamil therapy. In a group of 33 consecutive patients admitted to the Coronary Care Unit with unstable angina pectoris and treated with verapamil and nitroglycerin, we pro-spectively tested the hypothesis that plasma concentrations of verapamil were a direct determinant of resolution of ischemic symptoms over the initial 72-h period of admission. During this period, improvement or resolution of symptoms occurred in 23 of the 33 patients. With patients receiving 240 to 320 mg/day of verapamil, plasma verapamil concentrations varied between 8 and 487 ng/ml, rising significantly with increasing duration of therapy. Mean plasma verapamil concentrations were somewhat greater in patients who improved than in those with ongoing or worsening symptoms, but the differences were not statistically significant. Furthermore, no correlation was found between symptomatic status and plasma concentrations of norverapamil, the active metabolite of verapamil. In one patient cardiac failure worsened, possibly attributable to an elevated plasma verapamil concentration (336 ng/ml). We conclude that in this clinical setting there is little place for routine monitoring of plasma verapamil concentrations.

ISSN:0163-4356    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Sixty-two serum samples from 28 pediatric epileptic patients under treatment with phenytoin [diphenylhydantoin (DPH)] were obtained to study the correlation between total and free serum DPH concentrations. The effect of coadministered antiepileptic drugs on DPH protein binding was also studied. Binding of DPH to serum protein was assessed by ultrafiltration, and total and free DPH concentrations were determined by fluorescence polarization immunoassay. A strong correlation existed between the total and free concentrations [r= 0.958, p < 0.001, standard error of estimate (± 1Sγ) = 0.214]. The mean value for the DPH free fraction was 8.9% (range 5.7–16.3%). The samples obtained from patients on combination therapy with valproic acid (VPA) showed a larger DPH free fraction and greater variation. Exclusion of the 16 samples from patients concomitantly taking DPH and VPA yielded a better correlation (n = 46,r= 0.983, p < 0.001, ± 1Sγ = 0.145). The mean free fraction in the patients not taking VPA was 7.7% (range 5.7–9.0%). The effect of VPA on the protein binding of DPH was also studied by addition of the same antiepileptic drugs to normal human plasma; the results were similar to those obtained for epileptic patients. These findings suggest that the free DPH fraction can be predicted from the total concentration, even when the drug is coadministered with other antiepileptic drugs, the sole exception being VPA

ISSN:0163-4356    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

The kinetics of praziquantel was studied in normal andSchistosoma haematobium-infected Ghanaian subjects. There was a wide interin-dividual variation in half-life (t1/2),Cmax,Tmax, area under the curve (AUC) (0–8 h), and urinary recovery. No differences were noted between the two groups with regard toTmax, AUC (0–8 h), and t1/2. MeanCmaxwas higher in the patients than in the control subjects. The 8-hr urinary recovery of praziquantel was higher in the subjects with urinary schistosomiasis. The amount of praziquantel excreted unchanged in urine was 0.0052 ± 0.0027% (SD) of the dose for the control subjects and 0.0054 ± 0.0027% (SD) for the patients.

ISSN:0163-4356    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Serum phenytoin monitoring is frequently used in the management of epileptic patients because phenytoin has a narrow therapeutic index and exhibits nonlinear pharmacokinetics. This study prospectively evaluated serum phenytoin monitoring in an acute care teaching hospital. Two sets of criteria were established a priori to define (a) appropriate selection of patients with regard to serum phenytoin monitoring, and (b) inappropriate serum phenytoin determinations (SPDs). Eighty patients receiving phenytoin were studied, of whom 58 (72.5%) were appropriately selected. These included 35 patients (43.8%) for whom monitoring was indicated and was performed, and 23 patients (28.7%) for whom monitoring was not indicated and was not performed. There were 39 patients with no indications for serum phenytoin monitoring; however, 16 (41%) of them were monitored. A total of 113 SPDs were performed, of which 83 (73.5%) were deemed to be inappropriate. Seventy percent of SPDs resulted in phenytoin concentrations outside the usual therapeutic range (10–20 μg/ml). Overall, physicians appropriately selected patients with regard to serum phenytoin monitoring; however, when inappropriate selection did occur, it tended to involve monitoring of patients who did not require it. The majority of SPDs performed were deemed to be inappropriate, since they were done too soon after admission or a change in therapy to reliably indicate steady-state serum concentrations.

ISSN:0163-4356    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Requirements for regular-release oral theophylline were determined in 34 pediatric patients aged 0.25–14.8 years using orally derived pharmacokinetic data and the first-order absorption equation. Large ranges were found in the half-life (2.3–21.3 h) and calculated apparent volume of distribution (Vd) (0.300–1.54 L/kg). Mean serum theophylline concentration was more closely correlated with actual mean concentration (r= 0.61, p < 0.0002) when calculated with the individual patients'Vdvalues than with the standardVdof 0.5 L/kg (r= 0.31, NS), and predictions obtained with the individuals'Vdvalues were more precise (p < 0.05) and less biased than those obtained with the standardVd. The precision of prediction based on individualVdvalues was quantitatively similar (root mean squared error = 3.38 mg/L) to reported predictions based on pharmacokinetic values derived from an initial intravenous course of aminophylline therapy. We conclude that theophylline dosage requirements can be accurately estimated from orally derived pharmacokinetic data and that the method described may be useful for patients in whom intravenous therapy is not required or contraindicated.

ISSN:0163-4356    

出版商:OVID    

年代:1988

数据来源: OVID