摘要:

The pharmacokinetic and pharmacodynamic characteristics of heparin were studied in 10 healthy volunteers using the Hepcon/System B‐10. This coagulation‐monitoring system uses each patient's body weight, height, baseline activated clotting time (ACT), and heparin dose response values to determine initial heparin doses. We administered a calculated mean ± SD heparin dose of 85 ± 14 U/kg to 10 subjects to achieve a mean ± SD target ACT of 364 ± 29 seconds. This dose produced a mean ± SD measured peak ACT of 337 ± 53 seconds from a mean ± SD baseline of 121 ± 10 seconds. The measured peak ACT values resulting from the individualized heparin doses were within 20% of the desired peak in 9 (90%) of the subjects. Using the ACT values, the average mean residence time for heparin effect was 1.2 hours and half‐life was 0.8 ± 0.2 hours, with all the subjects' values returning to within 10% of baseline by 4 hours after the dose. Using the protamine‐derived heparin concentrations, heparin total‐body clearance ranged from 43 to 99 ml/hr/kg (mean ± SD 73.3 ± 14.5 ml/hr/kg). A linear relationship was found between heparin concentration and change in ACT that was described by ΔACT = 16.85 + 136.7 (heparin concentration). We conclude that this method is easy to perform and accurate for determining initial heparin dosage requirements, and could be an important improvement over existing approaches. In addition, it is a valuable research tool for studying heparin pharmacodynamics

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1990.tb03564.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Patients undergoing total knee arthroplasty were randomized to tourniquet inflation 1, 2, or 5 minutes after a 1‐g dose of cefazolin. Serum, soft tissue, and bone samples were obtained at 10, 30, and 60 minutes after inflation, immediately prior to tourniquet release (PTR), and 5 minutes after release. Areas under the concentration‐time curve (AUC10‐PTR) were calculated using the linear trapezoidal method and normalized to actual body weight, creatinine clearance, and length of tourniquet inflation. The percentage of penetration was calculated using the normalized values for the respective AUCs. Differences among the groups were analyzed using analysis of variance or the Kruskal‐Wallis test where appropriate. Groups were similar for age, actual body weight, duration of tourniquet inflation, and creatinine clearance (p>0.05). The median percentages of penetration for soft tissue and bone at 5, 2, and 1 minute were 14.5% and 4.6%, 6.7% and 3.0%, and 5.9% and 4.6%, respectively. Only the percentage of soft tissue penetration between 5 and 1 minute was significantly different (p = 0.015). Gender and type of anesthesia (general, epidural) had no effect on cefazolin penetration into soft tissue or bone. Although increasing the time interval between cefazolin administration and tourniquet inflation resulted in higher soft tissue drug concentrations, a 1 ‐ minute interval resulted in soft tissue and bone cefazolin concentrations at or above the minimum inhibitory concentration for microorganisms likely to be encountered in this surgical

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1990.tb03565.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

One hundred five patients receiving concurrent aminoglycoside and vancomycin therapy of at least 5 days' duration were retrospectively reviewed for development of nephrotoxicity. All had their vancomycin and aminoglycoside serum concentrations controlled by a clinical pharmacokinetics service. Nephrotoxicity occurred in 28 (27%) of the patients. Twenty‐two of the 28 had other factors that are known to contribute to renal failure (amphotericin B therapy, sepsis, liver disease, obstructive uropathy, pancreatitis, anesthesia). The remaining six developed nephrotoxicity without other known contributing factors. Logistic regression analysis revealed associations between nephrotoxicity and age, sex, aminoglycoside trough and vancomycin peak and trough serum concentrations, length of aminoglycoside and vancomycin therapy, concurrent amphotericin B therapy, liver disease, neutropenia, and peritonitis (p<0.05). In addition to factors previously reported, this study found that neutropenia and peritonitis are associated with an increased risk of nephrotoxicity. Patients with one or more risk factors warrant close monitoring of renal function as well as vancomycin and aminoglycoside serum concentration

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1990.tb03566.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

This clinical study assessed the influence of pentoxifylline and its metabolites on steady‐state serum theophylline concentrations. Nine healthy volunteers took sustained‐release formulations of pentoxifylline, theophylline, and a combination of both agents each for 7 days at standard therapeutic doses in a randomized order. Serum theophylline concentrations were analyzed using fluorescence‐polarization immunoassay (TDx) technique. During the pentoxifylline treatment phase, serum theophylline concentrations were undetectable, demonstrating the lack of assay interference from pentoxifylline and its metabolites. Mean trough steady‐state serum theophylline concentrations were 30% higher (p<0.05) during the combination treatment phase compared to theophylline administration alone, and varied considerably. Although side effects were more frequent during the combination phase, differences in the number of adverse reactions did not achieve statistical significance. This study demonstrates an interaction between theophylline and pentoxifylline, and indicates that close monitoring of serum theophylline concentrations during combination therapy is wa

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1990.tb03567.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Three hundred fifty outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double‐blind basis, to receive a single oral dose of aspirin 650 or 1000 mg, caffeine 65 mg, a combination of aspirin 650 mg with caffeine 65 mg, or placebo. Using a self‐rating record, subjects rated their pain and its relief hourly for 6 hours after medicating. Estimates of summed pain intensity difference, peak pain intensity difference, total relief, peak relief, and hours of 50% relief were derived from these subjective reports. All active treatments except caffeine were significantly superior to placebo. Pairwise comparisons indicated the aspirin‐caffeine combination was statistically superior to aspirin 650 mg alone for hours of 50% relief among patients who had severe baseline pain. Adverse effects were transitory and none were se

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1990.tb03568.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

In a case‐control study of 121 young insulin‐dependent diabetics diagnosed as having an episode of hypoglycemia, the relative risk estimate comparing human with animal insulins was 0.8 (95% confidence interval 0.4, 1.6) controlling for age, general practice, and calendar time. We conclude that in this study population derived from general practices in the United Kingdom, the risk of hypoglycemia was no higher in users of human insulin than it was in users of animal insul

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1990.tb03569.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

In a 10‐year (1979–1988) follow‐up study of young insulin‐dependent diabetics carried out at Group Health Cooperative of Puget Sound, the frequency of hospitalization for hypoglycemia remained constant. During the early years only animal insulins were available; during the latter years, human insulins were used in a majority of patients. The adjusted relative risk estimate for hospitalizations for hypoglycemia comparing users of human with users of animal insulins was 0.6 (95% confidence interval 0.2, 2.3). We conclude that the use of human insulins is not associated with an increased risk of hospitalization for hypoglycemia as compared with animal insulins in this pop

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1990.tb03570.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Based on one‐compartment pharmacokinetic model, the equations to calculate the specific fractional steady‐state of drug level achieved at any time (FSS) after administration of intravenous bolus, constant infusion, and oral immediate‐release preparations are reviewed. Also the equation to calculate FSS after administering an oral sustained‐release dosage form is derived. From these equations, it can be shown that the drug FSS after these routes of administration is dependent primarily on the elimination rate constant (K). However, for a sustained‐release preparation, the FSS is dependent on K, drug release rate constant (K1), as well as the fraction of sustained release (Fs) of the dosage form. Using the new derived equation for FSS, several simulations were performed to evaluate the effects of K1K, and Fs. These indicate that the time to achieve a given FSS is prolonged as K1or K becomes smaller and as Fsbeco

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1990.tb03571.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

We observed the effect of aminophylline administration on estimated hepatic blood flow. Indocyanine green (ICG) 0.5 mg/kg was administered as an intravenous bolus dose before and after intravenous infusion of 7 mg/kg aminophylline. Venous blood was collected at timed intervals over 15 minutes to construct ICG concentration‐time graphs. Pharmacokinetic values were calculated using non‐compartmental methods. Estimated hepatic blood flow decreased from 790 ± 190 to 665 ± 100 ml/minute (p<0.05) after administration of aminophy

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1990.tb03572.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Malathion is an organophosphate pesticide that can cause respiratory failure and death in humans. In vitro studies suggested that hemoperfusion may be valuable in treating malathion poisoning. We found that although the charcoal column may effect reasonable clearance in the first 2 hours of use, prolonged hemoperfusion may require changing the column in severe, acute poisonings.

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1990.tb03573.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY