摘要:

Strategies for treating pediatric malignancies have not only been successful (i.e., curative) for several disseminated childhood cancers, they have also served as paradigms for the therapy of many adult cancers. Initial strategies included combined treatment modalities (chemotherapy, surgery, radiotherapy) and combinations of different pharmacologic classes of anticancer drugs given in the appropriate schedules. Despite the currently successful therapy for some malignancies (e.g., 70% 4‐year disease‐free survival in acute lymphocytic leukemia), many children die without known reason. Recent advances in the clinical pharmacology of anticancer drugs have identified relationships between dose intensity and response (efficacy, toxicity). Traditional methods of measuring dose intensity (prescribed dose) have evolved to more sophisticated approaches in maximizing the intensity of treatment, with good response rates. Other methods of optimizing chemotherapy for individual patients include bone marrow support procedures and therapy with biologic response modifiers. Relatively few clinically useful new anticancer drugs have been discovered in the past several years. Fortunately, the potential to improve therapy with currently available agents has come about through enhanced knowledge of the biochemical and clinical pharmacology of anticancer drugs and biologic response modifiers, as well as improved understanding drug resistance biol

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1990.tb02590.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The present management of diabetes consists of attempting to control blood sugar tightly in the normal range and to treat individual complications such as neuropathy and retinopathy as they appear. Whereas these measures are perhaps effective in slowing the progress of diabetic complications, they do not cure the underlying process. The aldose reductase inhibitors have been investigated as possible remedies for various diabetic complications. Aldose reductase is an enzyme present in several human tissues that reduces glucose to sorbitol. In animal models there is evidence that the production of sorbitol is associated with the development of diabetic complications. Animal and human studies have tested the ability of aldose reductase inhibitors to halt or reverse diabetic complications. The weight of evidence leads to two conclusions: first, that aldose reductase inhibitors may bring significant relief to patients with certain diabetic complications; and second, that the current approach to proving clinical efficacy may not be adequate for these drugs.

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1990.tb02591.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

We cared for a 64‐year‐old woman who experienced increased serum creatinine levels after 8 days of ciprofloxacin therapy. She had previously received a course of several antibiotics, including gentamicin. Renal function returned to normal 18 days after the ciprofloxacin was discontinued. This is the eighth reported case of nephrotoxicity associated with this agent. The mechanism and predisposing factors have not been defi

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1990.tb02592.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Information on amphotericin B use patterns and infusion‐related adverse events were prospectively collected from 397 hospitalized adults. The methods of initiating amphotericin B varied greatly, with the majority of patients being gradually titrated to a full maintenance dose over 1–5 days. Overall, 71% of patients experienced at least one episode of an infusion‐related adverse event (IRAE) during the first week of therapy. Fever and chills were most commonly observed, with peak frequency on days 1 −3, followed by a subsquent decline. A wide variety of pretreatment medications were used to minimize IRAE; the most common regimens included some combination of diphenhydramine, acetaminophen, and corticosteroids, with or without heparin. The majority of patients (84.7%) received a test dose, and although none experienced a severe allergic reaction, one patient subsequently had an anaphylactic episode on the third day of amphotericin B therapy. The use of a test dose and the titration process are attempts to avoid the IRAE frequency associated with large initial doses of amphotericin B, but we observed that they provided little or no benefit. In addition, our study suggests that pretreatment regimens are frequently used in conjunction with the test dose. If the intent of the test dose is to identify patients sensitive to amphotericin B, pretreatment drugs may minimize these adverse events and prevent a complete evaluation of response to the te

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1990.tb02593.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Heparin pharmacokinetics and pharmacodynamics were studied in 17 patients undergoing hemodialysis, once a week for 4 weeks in order to evaluate intrapatient variability over time. A single bolus injection of heparin was administered directly into the circulation immediately prior to the start of hemodialysis in doses ranging from 3000 to 12,000 U. Blood samples were obtained to determine activated coagulation times (ACT) and heparin concentrations (HC). Combined zero‐ and first‐order elimination was seen in each of the 4 weeks. The half‐life of heparin decreased from beginning to end of hemodialysis during each week, with the percentage of decrease from the start of dialysis ranging from 70–74%, indicating concentration‐dependent elimination. Since the zero‐order component did not appear to be clinically significant, first‐order elimination was assumed. A linear decline in ACT over the time of the dialysis period was also seen during each week. A profile of ACT versus HC was generated for each patient as well as for the mean data to assess the relationship of HC to response. An excellent correlation was found for both individual patient data and mean data. In the third week the patients were randomized to receive standard treatment or an individualized dose. They were then crossed over to the opposite group in the fourth week to see if this relationship between ACT and HC would be useful in predicting heparin dose. These profiles were used to individualize the dose during either the third or fourth week of the study. No significant differences were noted between actual and predicted ACT. A significant degree of interpatient variability was demonstrated. Since no such variability was found when elimination rate constant, half‐life, clearance, distribution volume, and ACT were compared over the 4‐week study period, however, pharmacokinetic and pharmacodynamic profiling of patients when hemodialysis is first initiated may be useful for dosing heparin during subsequent hem

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1990.tb02594.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

In a randomized, crossover study the influence of enteral feedings (Ensure) on the absorption of theophylline from a sustained‐release preparation (Theo‐24) was evaluated. Six healthy, male subjects, age 22 to 37 years, participated. In phase 1 the subjects received a single oral dose of Theo‐24 6 mg/kg with 100 ml of water at 8:00 a.m. In phase 2, they received 100 ml boluses of Ensure hourly, beginning 3 hours prior to the oral dose and continuing for a total of 1000 ml. In phase 3, subjects received a single 30‐minute intravenous infusion of an equivalent dose of aminophylline. After each dose, serial blood samples were collected for 72 hours. No statistically significant differences in area under the curve (AUC∞0) (126.0 vs 127.3 μg hr/ml), maximum concentration (3.80 vs 4.08 μg/ml), or time to peak plasma level (13 vs 11 hrs) were found between phases 1 and 2. Mean AUC∞0for the intravenous phase (161.4 μg hr/ml) was significantly higher than the AUC for either oral study (p<0.05). The mean bioavailability was 81 % for phase 1 and 80% for phase 2. Percent absorbed versus time plots revealed no difference in rate of absorption between treatments. We conclude that short‐term administration of the enteral feeding Ensure does not influence the absorption of theophylline when administered as the sustained‐relea

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1990.tb02595.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

We evaluated the effect of glycated albumin on phenytoin protein binding in 36 elderly (age range 63–94 yrs) patients with type II diabetes mellitus (DM) under diet management. Serum was spiked with 15 mg/L phenytoin and incubated. A serum ultrafiltrate was obtained from each sample for determining total and free phenytoin concentrations. Glycated hemoglobin was determined by boronate‐affinity chromatography, and glycated albumin was separated from nonglycated fractions with boronate‐agarose gel. Glycated hemoglobin in the study group ranged from 4.3–14.6% (mean 7.8 ± SD 2.1%) and glycated albumin ranged from 3.7–12.5% (7.4 ± SD 2.6%). We observed no correlation between glycated albumin and the percentage of free phenytoin (r2= −0.14; p = 0.419). The concentration of nonglycated albumin ranged from 0.66‐4.28 g/dl (mean 3.45 ± 0.67 g/dl) and was calculated from measured total and glycated albumin concentrations. A correlation between the free fraction of phenytoin and nonglycated albumin was not demonstrated (r2= 0.22, p = 0.22). In addition, a correlation was not observed between total glycated albumin and the free fraction of phenytoin (r2= −0.095; p = 0.58). We conclude that elderly patients with type II DM under diet control do not have significant alterations in phenytoin protein binding. The use of total serum phenytoin levels therefore appears appropriate for determining phenytoin dosages in elderly patients with well con

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1990.tb02596.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY