摘要:

The clinical use of cyclosporine A (CsA) is complicated by large intra- and interindividual variabilities in its pharmacokinetics. Several factors contribute to these variabilities. This review aims at describing these factors and their relative contribution in the clinical situation. Cyclosporine A has a highly variable absorption. The absorption is dependent on the liver function, bile flow, and gastrointestinal status. A large fatty meal may increase the absorption of CsA. Impaired absorption is observed postoperatively. The vehicle or dosage form is of no importance for the absorption. The distribution of CsA is mainly influenced by the lipoprotein concentration in plasma and to a lesser extent by the haematocrit. However, age, gender, and obesity are of no clinical importance for the distribution. The metabolism is presumably genetically determined and the rate of metabolism varies greatly between individuals. Furthermore, the rate of metabolism is age-related and may be affected by concomitant medication. Factors of limited importance for the metabolism include sex, lipoprotein pattern, and drug concentration. Factors such as time after transplantation, haemodialysis, haematocrit, obesity, and uremia are not associated with altered metabolism. Thus, the major factor for the intraindividual variability in CsA-kinetics is the variable absorption, whereas the major cause for the interindividual variability supposedly is the inherited capacity to metabolize the drug. The factors mentioned above and other factors, found to be of minor or no importance for the kinetics of CsA, are discussed in detail.

ISSN:0163-4356    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Plasma samples from 237 patients with osteoarthritis treated with 750 mg naproxen daily were obtained after four weeks of active therapy. The samples were subjected to equilibrium dialysis, analyzed by high-performance liquid chromatography, and free concentrations and unbound fractions were determined. Within the free plasma concentration range in this large patient group, we could detect no association between free naproxen concentration and efficacy score or between free concentrations and adverse events. Free concentrations were 0.295 ± 0.260 üg/ml (mean ± SD) and unbound fractions were 0.33 ± 0.24%. Females had 65% higher free concentration compared to males (p< 0.001). For females, but not for males, there was a statistically significant correlation (p< 0.005) between age and free concentration. The free concentration was estimated to be 88% higher in an 80-year-old female compared to a 50-year-old. Females had a 41% higher unbound fraction than males (p< 0.005). For females, but not for males, a statistically significant relationship between age and unbound fraction was found. The unbound fraction was estimated to be 62% higher in an 80-year-old female than in a 50-year-old.

ISSN:0163-4356    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Although the tricyclic antidepressant dothiepin is often encountered in deliberate self-poisonings, there are no published studies of its disposition in overdose. In the present study, we have documented the plasma disposition of dothiepin and its major metabolites in eight overdose patients. All had high initial levels of dothiepin (819–3,851 üg/L), dothiepin-S-oxide (655–2,162 üg/L). nordothiepin (88–422 üg/L), and nordothiepin-S-oxide (176–530 üg/L) that were considerably above steady-state therapeutic concentrations. In three patients who received treatment with repeated-dose activated charcoal, dothiepin half-lives were 10.6, 12.5, and 13.1 h compared with the literature range of 18.5–24 h. All patients survived and none experienced any significant cardiovascular event despite exhibiting clinical signs of tricyclic antidepressant overdose. We suggest that repeated-dose activated charcoal treatment may decrease the dothiepin half-life after overdose.

ISSN:0163-4356    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Hypertension has emerged as a frequent side effect in transplant recipients on effective doses of cyclosporine (CsA). To control hypertension in renal transplant patients, calcium channel blockers have been used; some of these, however, have been shown to cause significant increases in CsA levels. These findings point out that possible interactions of each calcium antagonist with CsA deserve investigation. We performed an open, placebo-controlled study in 12 stable renal transplant recipients to determine whether short-term isradipine influences CsA pharmacokinetics. All patients had mild to moderate hypertension and received triple immunosuppressive therapy with CsA, azathioprine, and prednisolone. Throughout a 4-week period of isradipine treatment, blood CsA levels (specific and nonspecific monoclonal antibodies) remained stable. The mean trough specific level was 121 ± 14 üg/L following placebo, compared to 120 ± 14 üg/L during isradipine. Corresponding nonspecific values were 465 ± 68 and 474 ± 63 üg/L. Also, values forCmax, AUC, andt1/2were not significantly changed following 4 weeks of isradipine. Mean arterial pressure was significantly reduced at the end of the study. This study implies that isradipine does not influence CsA metabolism. Further studies should be carried out to determine its long-term effects on CsA pharmacokinetics and renal function in transplanted patients.

ISSN:0163-4356    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The pharmacokinetics of quinine was investigated in patients with acute falciparum malaria treated with quinine alone or in the presence of doxycycline. Twenty-six patients divided into two groups of equal number were enrolled in the study. In the absence of doxycycline, the volume of distribution of quinine (mean ± SD) was estimated to be 1.32 ± 0.32 L/kg, and its clearance was 0.125 ± 0.47 L/h/kg, which was only in partial agreement with previously published data. No effect of doxycycline on the pharmacokinetics of quinine was observed.

ISSN:0163-4356    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Amikacin's pharmacokinetics and dosage requirements were studied in 98 patients receiving treatment for gram-negative infections. A wide interpatient variation in the kinetic parameters of the drug occurred in all patients and in patients who had normal serum creatinine levels or normal creatinine clearance. The half-life ranged from 0.7 to 14.4 h in 74 patients who had normal serum creatinine levels and from 0.7 to 7.2 h in 37 patients who had normal creatinine clearance. The necessary daily dose to obtain therapeutic serum concentrations ranged from 1.25 to 57 mg/kg in patients with normal serum creatinine levels and from 10 to 57 mg/kg in patients with normal creatinine clearance. In four patients (4%), a significant change in baseline serum creatinine level (> 0.5 mg/dl) occurred during or after treatment, which may have been amikacin-associated toxicity. Overt ototoxicity occurred in one patient. The method of individualizing dosage regimens provided a clinically useful means of rapidly attaining therapeutic peak and trough senum concentrations.

ISSN:0163-4356    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Two simple nomograms for individualizing the phenytoin dose in adults and children based on two or more steady-state plasma or serum levels (Css) at different daily doses are described. The nomograms allow one to plot, detect, and exclude abnormal points due to noncompliance, interactions, or laboratory errors, to draw the best line for the remaining points, and to estimate the dose necessary to reach a desiredCsswithout calculations but with the same accuracy as more complex computer-dependent methods based on calculation ofVmaxandKmax. Our nomograms may be a practical aid in adult or pediatric practice.

ISSN:0163-4356    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Characterization of antibiotic pharmacokinetics in patients with renal insufficiency may be complicated by interfering substances within the assay. We compared three different assays for teicoplanin in serum and dialysate of 10 hemodialysis and six continuous ambulatory peritoneal dialysis (CAPD) patients. The microbiological assay (micro) had a within-run and between-run coefficient of variation (%CV) of < 7.5% for concentrations ranging from 0.2 to 96 üg/ml. The high-performance liquid chromatographic assay (HPLC) within-and between-run %CV was < 8% for concentrations ranging from 1 to 80 üg/ml. The fluorescence polarization immunoassay (FPIA) within- and between-run %CV was < 7% for concentrations ranging from 5 to 100 üg/ml. In serum of hemodialysis patients FPIA results were slightly higher than HPLC results: FPIA = 1.11 HPLC + 2.37 (r= 0.975, n = 202), and FPIA concentrations in serum were also slightly higher than those measured by micro (FPIA = 1.21 micro – 1.57,r= 0.972, n = 161). The HPLC and micro serum results were also comparable in hemodialysis patients: micro = 0.92 HPLC + 2.89,r= 0.953, n = 160. However, in CAPD patients micro results were lower than HPLC results in serum (micro = 0.82 HPLC + 0.49,r= 0.981, n = 262). In peritoneal dialysate, HPLC values were 60% of the micro values. Thus, FPIA may be the optimal technique for therapeutic monitoring of teicoplanin in the clinical setting due to its simplicity, specificity, and good correlation to HPLC and micro.

ISSN:0163-4356    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Reagents are now available for the measurement of a range of antiepileptic drugs by fluorescence polarisation immunoassay using the Roche Cobas Fara II analyser. Evaluation data are presented that demonstrate that these assays represent a convenient, cost-effective, and analytically reliable alternative to other commercially available systems for the measurement of drugs during therapeutic drug monitoring. The use of a general-purpose analyser, the opportunity to perform different drug assays simultaneously, and long calibration stability confer significant benefits on these methods. These are especially applicable for the laboratory that undertakes only small or moderate numbers of such investigations during therapeutic drug monitoring.

ISSN:0163-4356    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The TDx digoxin II immunoassay was used in controls and in patients not taking digoxin or any other cardiac glycoside. We report the frequency of interference thought to be caused by digoxin-like factors (DLFs). We found a high incidence of false-positive results in 15 patients with severe hepatic disease (60% false-positive results). In newborn infants we found false-positive results both when their blood was drawn from a peripheral vein (89% false-positive results) and, more strikingly (100% false-positive results), when it was obtained from an umbilical cord vein (p> 0.001). Compared to a control group, no statistically significant false-positive results were found in patients with mild to moderate chronic renal failure (n = 21) or in pregnant women (n = 15). In patients with chronic renal failure undergoing hemodialysis six of 25 had false-positive results. These results suggest that digoxin levels must be interpreted carefully in patients with chronic liver disease and chronic renal failure and in newborns until new methods that eliminate the interference caused by DLFs become readily available.

ISSN:0163-4356    

出版商:OVID    

年代:1991

数据来源: OVID