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Biomedical subjects

R A Pleasants

Publications and source records attributed to R A Pleasants.

At least 19 recordsLinked to original sources
PubMed1996

Pharmacokinetics of vancomycin in adult cystic fibrosis patients.

Although the depositions of many antibiotics are altered in cystic fibrosis patients, that of vancomycin has not been studied. To assess vancomycin pharmacokinetics, 10 adult cystic fibrosis patients were given a parenteral dose of vancomycin (15 mg/kg) during the first 72 h of hospitalization for acute bronchopulmonary exacerbation. Blood samples were obtained at 0, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 15, and 24 h. The mean (standard deviation) weight, measured creatinine clearance, and Taussig clinical score were 51 (13) kg, 130 (39) ml/min/1.73 m2, and 64 (13), respectively. Multicompartmental pharmacokinetic parameters were best described by a two-compartment model. The mean (standard deviation) volume of distribution, total body clearance, and terminal elimination rate constant were 0.58 (0.15) liter/kg, 91 (19) ml/min/1.73 m2, and 0.123 (0.05) h-1, respectively. These values were consistent with vancomycin pharmacokinetic parameters obtained in previous studies of healthy adult volunteers. Vancomycin dosages predicted by using a two-compartment Bayesian model were approximately 15 mg/kg every 8 to 12 h. There were poor correlations between clinical score or creatinine clearance and any pharmacokinetic parameter (r values of < 0.32). The coefficient of correlation between urine flow rate and total body clearance was 0.7 (P < 0.05). Adult cystic fibrosis patients exhibit a disposition of vancomycin similar to that exhibited by healthy adults, and thus cystic fibrosis does not alter vancomycin pharmacokinetics.

Adult↗
PubMed1994

Allergic reactions to parenteral beta-lactam antibiotics in patients with cystic fibrosis.

Certain antibiotics, particularly piperacillin, have been reported to be associated with a high incidence of allergic reactions in patients with cystic fibrosis. We initiated a study to determine the relative frequency of allergic reactions, ie, drug-induced fever and rash, to parenteral beta-lactam antibiotics in adult patients with cystic fibrosis. Charts of 111 patients were reviewed for each hospitalization to assess allergic reactions. Of 90 evaluable patients, 26 patients developed one or more allergic reactions to beta-lactam antibiotics. The number of allergic reactions per number of patients receiving specific antibiotics were carbenicillin (4/56), mezlocillin (7/42), piperacillin (11/31), ticarcillin (1/20), cefazolin (0/24), ceftazidime (1/35), imipenem/cilastatin (4/16), and nafcillin (3/36). The mean time to onset of drug-induced fever or of rash was 9.1 days. As a group penicillins had a higher frequency of allergic reactions than cephalosporins. The frequency of reactions was greatest with acylaminopenicillins (mezlocillin and piperacillin) and imipenem/cilastatin. The results of this study indicate that in addition to piperacillin, mezlocillin and imipenem/cilastatin may be associated with a high incidence of allergic reactions in patients with CF.

Adult↗
PubMed1993

Arthropathy secondary to ciprofloxacin in an adult cystic fibrosis patient.

OBJECTIVE: To report a case of possible ciprofloxacin-induced arthropathy in an adult patient with cystic fibrosis (CF). CASE SUMMARY: A 25-year-old man with CF received three separate courses of ciprofloxacin therapy at usual doses for acute pulmonary exacerbations of his disease. During the second and third courses, the patient experienced bilateral swelling of his knees between two to three weeks after initiation of each course. Both times symptoms markedly decreased after discontinuation of the drug. The patient had no prior history of arthropathy. Furthermore, during the last two acute exacerbations of his CF, he did not receive ciprofloxacin and did not experience any symptoms of arthropathy. DISCUSSION: Prior cases of quinolone-induced arthropathy involving pediatric CF patients or adult patients without CF have been reported in the literature. We report the first case of such an arthropathy in an adult patient with CF. The findings are supported by a rechallenge with the drug. CONCLUSIONS: It is likely that ciprofloxacin may produce arthropathy in adult as well as pediatric patients with CF. Quinolones should be considered as a possible cause of arthropathy in adult CF patients.

Adult↗
PubMed1992

Compatibility of ceftazidime and aminophylline admixtures for different methods of intravenous infusion.

OBJECTIVE: Aminophylline and ceftazidime are sometimes used concurrently in patients with respiratory disorders. Parenteral aminophylline usually is administered as a constant infusion, and ceftazidime is given intermittently or less commonly as a constant infusion. We evaluated the stability and compatibility of the two drugs when aminophylline is given as a constant intravenous infusion and ceftazidime is administered simultaneously either through a y-site (piggyback method) or as a continuous infusion (constant infusion method). DESIGN: The chemical stability of intravenous aminophylline and ceftazidime in dextrose 5% and NaCl 0.9% for both methods was studied. Three different formulations of ceftazidime from the same manufacturer were studied (minibag using reconstituted ceftazidime, premixed minibag, and ceftazidime arginine). For the piggyback and constant infusion methods, samples were collected at 0, 1, and 2 hours; and 0, 6, and 24 hours, respectively. All experiments were conducted in triplicate. Samples were analyzed in duplicate by a stability-indicating HPLC assay method. OUTCOME MEASURE: Ceftazidime and aminophylline were considered stable if concentrations remained above 90 percent of the original concentrations over the time periods studied. RESULTS: Ceftazidime was determined to be compatible with aminophylline in the piggyback method. In contrast, when aminophylline and ceftazidime were admixed in the same intravenous container (constant infusion method), the two drugs were not stable. CONCLUSIONS: These data indicate that aminophylline and ceftazidime admixtures are incompatible when prepared in the same intravenous container, which may occur if both are given as a constant infusion. The two drugs are compatible when the ceftazidime is piggybacked into a primary intravenous set in which aminophylline is administered as a constant infusion.

Aminophylline↗
PubMed1991

Use of antimicrobial drugs in adults before and after removal of a restriction policy.

The effects on the quantity and quality of antimicrobial drug use of removing an antimicrobial restriction policy are reported. Monthly totals for the number of courses of antimicrobial therapy and expenditures based on grams used were obtained from pharmacy records on adult inpatients for a portion (July-December 1987) of the restriction policy term and for the six months (July-December 1988) immediately after the policy ended. Data were obtained for nine restricted drugs and for three that were never restricted. Retrospective drug-use reviews were conducted for ceftazidime and imipenem-cilastatin. For the restricted agents, the total number of courses of therapy increased by 158% after the restriction policy was removed, and total expenditures increased by 103%. There were no significant changes in the number of courses of therapy or cost for the unrestricted antimicrobials. In the postrestriction period, ceftazidime and imipenem-cilastatin were used more often in patients who were less critically ill. Inappropriate use of imipenem-cilastatin occurred significantly more often after the restrictions were removed. Other factors potentially affecting the use of antimicrobials, such as patient age and the incidence of nosocomial infections, did not differ substantially between the two periods. The removal of an antimicrobial restriction policy resulted in increased use of and higher expenditures for previously restricted agents, as well as an increase in the inappropriate use of at least one agent.

Adult↗
PubMed1989

Reassessment of cross-reactivity of spironolactone metabolites with four digoxin immunoassays.

Spironolactone and one of its metabolites, canrenone, cross-react with some digoxin immunoassays to result in erroneous serum digoxin concentrations. Recently, additional compounds, 7-alpha-thiomethylspirolactone (7-a-TMS) and 6-beta-hydroxy-7-alpha-thiomethylspirolactone (6-B-OH-7-a-TMS), have been reported to be quantitatively important metabolites of spironolactone. This study was initiated to evaluate the cross-reactivity of these metabolites, canrenone, and spironolactone with four different digoxin immunoassays. Blank serum was spiked with each compound to yield concentrations reported to occur in vivo. Samples were analyzed in duplicate by each of the following immunoassays: fluorescence polarization immunoassay (FPIA); affinity-column-mediated immunoassay (ACMIA); radioimmunoassay (RIA); and enzyme immunoassay (EIA). The 7-a-TMS metabolite cross-reacted with both the RIA and ACMIA methods. Apparent digoxin concentrations were as great as 0.39 ng/ml for this metabolite at the highest concentration evaluated, 600 ng/ml. At the lowest concentrations evaluated with the 7-a-TMS metabolite, 50 ng/ml, apparent digoxin concentrations as high as 0.28 ng/ml were reported. The 6-B-OH-7-a-TMS metabolite did not cross-react to a significant extent with any of immunoassays studied. Canrenone cross-reacted with the ACMIA method at a concentration of 100 ng/ml. The EIA method exhibited no apparent cross-reactivity with any of the compounds, whereas the FPIA method exhibited minimal cross-reactivity. The results of this study indicate that the 7-a-TMS metabolite cross-reacts to a significant extent with some immunoassays; however, this is not true for the 6-B-OH-7-a-TMS metabolite.

Adult↗
PubMed1989

Tobramycin administration and blood sampling through a dual-lumen peripheral intravenous catheter.

The objective of this study was to determine if a peripheral dual-lumen catheter could be used for accurate tobramycin blood concentration measurement when drug administration and blood sampling were undertaken through separate lumens of the catheter. Eleven adult volunteers received tobramycin 1.5 mg/kg iv infused over 30 minutes through the distal lumen of the dual-lumen catheter every eight hours for two doses. Multiple blood samples were obtained concurrently from the proximal lumen of the catheter and a single-lumen catheter in the contralateral arm after each dose. Blood samples were also obtained through the distal lumen before and 30 minutes after the end of the infusion. Accurate blood samples were obtainable through the dual-lumen catheter in only 5 of 11 subjects due to either infiltration or difficulties in catheter placement. In the subjects from whom accurate blood samples were obtained, approximately 20 minutes postinfusion was the amount of time required before measured tobramycin serum concentrations were similar between the arm in which the drug was infused (site of the dual-lumen catheter) and the contralateral arm. At standard times for obtainment of trough (just prior to the infusion) and peak (30 minutes after the end of a 30-minute infusion) tobramycin serum concentrations from the proximal lumen of the dual-lumen catheter were numerically similar to those obtained from the contralateral arm. This preliminary study indicates that the dual-lumen catheter provides accurate aminoglycoside concentrations when patent relative to blood withdrawal and if peak blood samples are obtained at least 30 minutes postinfusion through the recommended lumen. However, further study in a larger number of subjects is required before routine use of this device can be recommended.

Adult↗
PubMed1988

Effect of data collection method on results of serum digoxin concentration audit.

The appropriateness of serum digoxin concentration (SDC) orders was evaluated with respect to indication for use, sampling time, and action taken by physicians when the reported SDC was out of the normal therapeutic range; the effect of the two data-collection methods used (retrospective and concurrent audits) on the results was studied. Criteria for the appropriate use of SDCs were approved by the medical staff through the pharmacy and therapeutics committee. Patients on adult medicine services were entered into the study as daily SDC determinations were reported by the clinical laboratory. Most of the SDCs were evaluated using approved criteria by primary pharmacist clinicians who were concurrently monitoring drug therapy and participating with the treatment team. A retrospective audit of the same patients was conducted, using only chart review. A total of 134 SDCs involving 78 patients were evaluated. Concurrent-audit results indicated that 18.7% of the SDCs were ordered without an appropriate indication, 16.4% were sampled incorrectly with respect to proper timing, and 8.2% did not result in dosage adjustments when indicated. With respect to appropriate sampling time and overall use of SDCs, significantly more SDCs met the standards under concurrent audit than under retrospective audit. The retrospective chart review method of auditing may not detect as much pertinent information as is desirable.

Concurrent Review↗
PubMed1988

Accuracy of tobramycin delivery by four i.v. infusion methods.

The accuracy of tobramycin delivery by four methods of intermittent intravenous infusion was studied in 11 healthy male volunteers. Subjects received intravenous tobramycin (as the sulfate salt) 1.5 mg/kg by each of four infusion methods in a nonblinded, randomized, four-way crossover design. The methods used for intravenous infusion were (1) minibag via gravity flow (MG), (2) minibag with the secondary infusion tubing inserted below a volumetric infusion pump (MP), (3) metered chamber via volumetric infusion pump (MC), and (4) syringe pump (SP). Doses were diluted to a volume of 50 mL, except for the two minibag methods, for which the dilution was necessarily greater because of manufacturer overfill. Intravenous flow rates for both primary fluid and drug administration were set at 100 mL/hr, and the duration of drug infusion was documented by observation for each administered dose. The fluid volume of 12 minibags was measured to assess manufacturer overfill. Fluid remaining in the secondary i.v. tubing for the minibag methods was collected after the infusion. Seventeen blood samples were obtained before and at various time intervals after each dose and analyzed in duplicate for tobramycin content by fluorescence polarization immunoassay. A mean of 10% of each dose remained in the secondary i.v. tubing at the completion of the infusion for the minibag methods, whereas less than 1% of each dose remained in the secondary tubing for the SP method.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Effect of four intravenous infusion methods on tobramycin pharmacokinetics.

The influence of four intermittent intravenous infusion methods on the determination of tobramycin pharmacokinetic values and predicted doses was evaluated in 11 healthy adult volunteers. Each subject received tobramycin (as the sulfate salt) 1.5 mg/kg by each of four i.v. infusion methods: (1) minibag via gravity flow (MG), (2) minibag with the secondary infusion tubing inserted below a volumetric pump (MP), (3) metered chamber via volumetric pump (MC), and (4) syringe pump (SP). Infusion rates were initially set to administer each dose over a 30-minute period. Sixteen blood samples were obtained over an eight-hour period before and at various time intervals after each dose and were analyzed for tobramycin content by fluorescence polarization immunoassay. Area under the serum concentration-time curve from time zero to infinity (AUC0-infinity) was calculated by the trapezoidal rule. Serum tobramycin concentration data for each subject were fitted to a biexponential decay model with zero-order input. beta and V beta were calculated from fitted data. One-compartment pharmacokinetic values, elimination rate constant (kappa), apparent volume of distribution (V), and predicted doses to achieve steady-state peak concentrations of 6 micrograms/mL were calculated by the method of Sawchuk and Zaske. There were no significant differences in either beta or kappa among the infusion methods. V beta values (mean +/- S.D.) for the methods were 0.240 +/- 0.025 (MG), 0.257 +/- 0.025 (MP), 0.221 +/- 0.027 (MC), and 0.231 +/- 0.032 (SP) L/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1987

Lack of apparent effect of assay methodology on the pharmacokinetics of digoxin.

The purpose of this study was to determine if serum digoxin concentration data using three different automated immunoassay methods would produce similar pharmacokinetic values in normal volunteer subjects. Area under the curve (AUC), steady-state volume of distribution/bioavailability ratio (Vd/F), terminal elimination rate constant (beta), clearance/bioavailability ratio (CL/F), maximum digoxin concentration (Cmax), minimum digoxin concentration (Cmin), and time of peak (Tp) were evaluated. Ten healthy volunteers received digoxin capsules 0.2 mg daily for 10 days. On day 10, 16 serial blood samples were collected over a 24-h dosing interval and analyzed by radioimmunoassay (RIA) (Concept 4, Micromedic Systems), fluorescence polarization immunoassay (FPIA) (TDx, Abbott Laboratories), and affinity column-mediated immunoassay (ACMIA), (aca, duPont Instruments). When comparing RIA and FPIA, the mean of the percent differences for AUC, Vd/F, beta, and CL/F were 9, 4, 10, and 6%, respectively. The mean of the percent differences were 2, 3, 44, and 6%, respectively, when comparing RIA and ACMIA. However, none of these differences were statistically significant. Although a trend toward higher Cmax values by RIA was noted, there was no statistical difference in Cmax, Cmin, and Tp. Orthogonal regression of all serum digoxin concentrations showed that FPIA = 0.76 RIA + 0.19, r = 0.967 (p less than 0.001); and ACMIA = 0.92 RIA + 0.04, r = 0.943 (p less than 0.001). At serum digoxin concentrations less than 1 ng/ml, FPIA overestimated RIA results (p less than 0.005), while ACMIA was approximately equal to the RIA results.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Proteins↗