Toward optimal provision of antithrombotic therapy.
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Anticoagulants↗
Biomedical subjects
W L Rock
Publications and source records attributed to W L Rock.
Adopting the INR system.
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Anticoagulants↗
Lack of effect of tacrine administration on the anticoagulant activity of warfarin.
The effect of tacrine administration on prothrombin time was studied in 13 patients receiving prolonged warfarin therapy. After a 3-week baseline period and 5 days of placebo administration, patients received 20 mg tacrine four times daily for 5 days. Prothrombin times were determined during baseline, daily before the morning doses of placebo and tacrine, and 14 days after the last tacrine dose (closeout). Mean (+/- SD) prothrombin times were 16.2 +/- 2.8 seconds at baseline, 15.1 +/- 2.6 seconds during the placebo phase, 15.8 +/- 3.6 seconds during the tacrine phase, and 15.3 +/- 3.6 seconds at closeout, indicating that tacrine has no effect on the anticoagulant activity of warfarin. Alteration of warfarin dosage should not be required in patients receiving concurrent tacrine therapy.
Aged↗
The effect of everyday exercise on steady state digoxin concentrations.
The purpose of this study was to evaluate the effect of 1 hour of everyday exercise (walking at patient's own pace) on serum digoxin concentrations. Nine white male subjects (ages 58-74) who had been taking the same digoxin dose for greater than 1 month participated. There were three continuous phases: 1 hour of rest, 1 hour of exercise, and a final hour of rest. Serum digoxin concentrations were drawn every 20 minutes. During the first rest period, serum digoxin concentrations rose 30% from the first concentration drawn in the study. After 1 hour of exercise, serum digoxin concentrations fell 26.8% from the last concentration of the first rest period. At the end of the second hour of rest, serum digoxin concentrations increased by 36.6% from the last concentration. Repeated measures analysis of variance demonstrated a significant (P less than .01) change in serum digoxin concentrations. Significant (P less than .01) differences were found between sampling times 0 and 60, 60 and 80, 60 and 100, 60 and 120 and 180 minutes using a paired t-test with Bonferroni correction. A weak correlation (r = 0.74, r2 = 0.55) between percent change in concentrations and age during the exercise phase was found, but there was no correlation between the percent change in concentrations and age during the two immobilization phases. Because significant changes in concentrations occurred during each phase of the study, we conclude that the influence of everyday exercise should be taken into account when interpreting serum digoxin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
Age Factors↗
Effects of cimetidine or ranitidine on the pharmacokinetics of flurbiprofen.
The effect of oral cimetidine or ranitidine on the pharmacokinetics of the nonsteroidal anti-inflammatory agent flurbiprofen was studied. Nine healthy volunteers participated in the study. The subjects were divided into three groups, and each group alternated therapy with each of the following treatments: flurbiprofen 200 mg (two 100-mg tablets), flurbiprofen 200 mg plus ranitidine 150 mg two times daily for seven days before and for two days after receiving flurbiprofen, and flurbiprofen 200 mg plus cimetidine 300 mg four times a day for seven days before and for two days after receiving flurbiprofen. Blood samples were collected at time zero and at various intervals during a 48-hour period. Serum flurbiprofen concentrations were determined by high-performance liquid chromatography. No significant differences in elimination rate constant, peak concentration, time to peak concentration, volume of distribution, or elimination half-life were noted among treatments. The difference in area under the curve (AUC) in subjects treated with flurbiprofen alone and in those treated with flurbiprofen plus cimetidine was significant. Two subjects experienced gastric upset; one case was apparently caused by cimetidine, and the other was likely caused by flurbiprofen. Although a significant increase in AUC was observed in subjects receiving flurbiprofen plus cimetidine, the interaction is probably not clinically important.
Adult↗
Antibacterial structure-activity relationships obtained with resistant microorganisms I: Inhibition of R-factor resistant Escherichia coli by tetracyclines.
Aparent partition coefficients and inhibitory activities against sensitive and resistant Escherichia coli were determined for 14 tetracyclines. The difference in the kinetics of inhibition of the two organisms is discussed in terms of their permeabilities. The partition coefficients were determined in an octanol-buffer system. Values for eight compounds were in general agreement with the literature; values for the remaining six compounds had not been reported previously. Growth of the organisms was determined by a single-point turbidimetric method in the presence and absence of tetracyclines. Inhibitory activities were obtained by a kinetic treatment. Derived rate constants for the sensitive organism were linearly related to antibiotic concentration. For the resistant organism and 12 compounds, the derived rate constants and antibiotic concentration were related in a manner typical of saturation kinetics. These inhibitory activities were related to the partition coefficients, while activities against the sensitive strain were not. These findings suggest that activity against the resistant strain is permeability controlled but that activity against the sensitive strain has a different rate-determining step.
Depression, Chemical↗