ABSTRACT
Forty-eight patients were enrolled in a clinical study of oral ciprofloxacin for the treatment of soft tissue or bone infections. Patients received 500 to 750 mg of ciprofloxacin every 12 hours. In the predominantly older population studied, there were 13 patients with osteomyelitis, 24 diabetic patients with soft tissue infection and probable osteomyelitis, and 11 patients with other soft tissue infections. Infecting pathogens included Pseudomonas aeruginosa in 25 patients, Serratia species in nine patients, Staphylococcus aureus in 13 patients, and other aerobic gram-negative rods in 21 patients. Clinical response (defined as resolution or improvement) was noted in 84 percent of patients with non-diabetic osteomyelitis, in 79 percent of patients with diabetic infections, and in 91 percent of patients with soft tissue infections. Microbiologic outcome was very favorable in 75 percent of cases, and Pseudomonas responded as well as any other pathogen. Pharmacokinetic properties of ciprofloxacin were evaluated in 12 patients, and the data were analyzed using both compartmental and non-compartmental analyses. Mean values for compartmental rate constants (hours-1) were as follows: absorption rate constant = 1.15; intercompartmental rate constants, k12 = 0.48, and k21 = 0.58; elimination rate constant = 0.46; distribution rate constant = 1.31; and terminal elimination rate constant = 0.19. The apparent volume of distribution at steady state/bioavailability was 196 liters and total body clearance/bioavailability was 45.9 liters/hour. The mean time to peak concentration was 1.3 hours. The mean peak concentration as determined by compartmental fitting (2.4 micrograms/ml) underestimated the observed peak (3.2 micrograms/ml) by 24.8 percent. Clearance of ciprofloxacin was similar regardless of the method used to fit the data, whereas the volume of distribution was significantly different when the two analysis techniques were compared. Ciprofloxacin was well tolerated, with the most frequent adverse reactions being rash, gastrointestinal intolerance, and increased levels of liver enzymes, each of which occurred in five patients.
Subject(s)
Bacterial Infections/drug therapy , Ciprofloxacin/therapeutic use , Osteomyelitis/drug therapy , Administration, Oral , Aged , Bacterial Infections/metabolism , Ciprofloxacin/administration & dosage , Ciprofloxacin/metabolism , Clinical Trials as Topic , Diabetes Complications , Humans , Kinetics , Middle Aged , Osteomyelitis/complications , Osteomyelitis/metabolism , SafetyABSTRACT
We evolved a nomogram for guiding and standardizing intravenous theophylline therapy in hospitalized patients. It provides rapid calculation of a loading dose based on body weight and previous therapy and a maintenance infusion rate related to three categories of expected metabolic activity. The guidelines were prospectively used in the treatment of 72 patients, mainly in a respiratory care unit. The nomogram was successfully used to attain near-steady-state serum concentrations in the therapeutic range of 8 to 20 mg/litre in 72% of patients, with only two patients outside of the range of 5 to 25 mg/litre. These guidelines facilitate initial theophylline dosage in older patients with liver and cardiac disease and provide a rational basis for interpreting serum concentration measurements and adjustment of drug therapy.
Subject(s)
Theophylline/administration & dosage , Adult , Age Factors , Aged , Body Weight , Female , Heart Diseases/drug therapy , Humans , Liver Diseases/drug therapy , Male , Middle Aged , New York , Reference Values , Respiratory Care Units , Theophylline/bloodABSTRACT
A young woman with spontaneous left pneumothorax had a phasic voltage alternation of her electrocardiogram that resolved with expansion of the lung. Likely explanations for this phenomenon are a respiratory dependent change in cardiac anatomy and a change in the volume conductor with respiration.
Subject(s)
Electrocardiography , Pneumothorax/diagnosis , Adult , Female , Humans , Intubation , Pneumonectomy , Pneumothorax/surgery , Radiography, Thoracic , RecurrenceABSTRACT
A system was developed for guiding theophylline therapy in acutely ill patients with respiratory disease and for recovery of pharmacokinetic information. A dosage regimen nomogram was designed based on literature data and preliminary pharmacokinetic studies in patients. Using the nomogram, physicians select the loading and infusion dosages based on previous therapy, body weight, age, and cardiac and hepatic status of the patient. Specifications are provided for loading (up to 5.6 mg/kg) and maintenance doses (0.9, 0.68, or 0.45 mg/kg/hr) of aminophylline, handling of i.v. dosage forms, and collection of three initial blood samples. Serum samples were assayed for theophylline by high-performance liquid chromatography for rapid feedback of data to the physician and computer estimation of body clearance values. The usefulness of the nomogram guidelines was examined prospectively in 72 patients. Near-steady-state serum concentrations in the therapeutic range of 8-20 mg/liter were found in 72% of the patients. Only two patients were outside of the range of 5-25 mg/liter. The relationship between the physician's estimate of the patient's clinical status (three classes) and measured body clearance was highly significant (p less than 0.025). A comprehensive data collection format allows further analysis of the factors responsible for the variability in theophylline disposition in patients undergoing therapy.
