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)

Estimation of the steady-state volume of distribution for digoxin: a comparison of model-independent methods with a two-compartment model in healthy volunteers.

Digoxin serum concentration vs. time data have been described in the literature by a linear two-compartment model. When calculating the steady-state volume of distribution for digoxin after oral dosing, a computer fitting program is often used because of the complex first-order absorption, two-compartment model employed. Since computer programs are not always available, we computed and compared the steady-state volume of distribution/bioavailability for digoxin using both a model-independent (area) and compartmental approach. Six healthy subjects participated in the study; each received digoxin 0.2 mg in capsule form daily for ten days. The mean steady-state volume of distribution/bioavailability calculated by noncompartmental analysis was 785 L and the mean for compartmental analysis was 784 L. The small difference between methods suggests that area analysis offers a simpler alternative to computerized compartmental fitting to determine this parameter for digoxin.

In vivo accuracy of gravity-flow i.v. infusion systems.

The accuracy of fluid delivery via gravity-flow i.v. infusion systems in hospitalized patients was evaluated. All adult patients on the medical-surgical wards of a university hospital who were receiving i.v. fluids via gravity-flow infusion sets were studied during a four-day period. Data collected approximately every two hours over a 15-hour period daily included the prescribed i.v. flow rate, type of i.v. set (microdrop or macrodrop), drop rate, and the approximate volume of fluid remaining in the i.v. container. Drop rates were measured with a photocell device placed around the drip chamber of the i.v. set. A total of 509 observations involving 86 patients were recorded during the study; drop rates were evaluated at flow rates for which there were 20 or more observations. For the majority of flow rates and set types, less than 15% of observations were within +/- 10% of desired drop rates, while only 21% of observations fell within +/- 20% of desired drop rates. Mean versus desired volume of fluid delivered between observations differed substantially but not as much as anticipated based on drop rate variability, reflecting nurses' attempt to adjust fluid therapy based on volume of fluid delivered. Intravenous fluid delivery via gravity-flow i.v. infusion systems is highly inaccurate. To ensure appropriate fluid delivery, better monitoring or improvement of i.v. fluid administration systems or the use of electronic infusion control devices is recommended.

Patient selection for serum gentamicin levels.

This article describes a set of criteria that can be used to select appropriate patients for serum gentamicin level (SGL) determinations. The set was generated through a critical review of the literature relevant to gentamicin pharmacokinetics and specific patient factors that can influence gentamicin elimination. Gentamicin was chosen because it has been widely used, and a large portion of the body of knowledge concerning aminoglycosides involves gentamicin. Using these criteria, we prospectively evaluated 73 Medical University Hospital patients for appropriateness of sampling. Forty-nine patients (67.2%) were appropriately selected for SGL measurement. This included patients who conformed to at least one criterion and received SGL determination(s), as well as patients who did not conform to any criterion and did not receive a SGL determination. Forty patients (54.8%) conformed to at least one criterion. Although the majority of patients were appropriately selected, only 40% of patients who met at least one criterion received SGL measurement(s). These data suggest the need for greater awareness by the clinician of factors that predispose patients to toxic or subtherapeutic gentamicin therapy.

Amphotericin B and flucytosine in the treatment of candidal cystitis.

The causes, diagnosis, and treatment of candidal cystitis are reviewed. It is necessary to differentiate between colonization and infection because Candida organisms reside normally in the digestive tract of humans and do not normally exist in the urine. A diagnosis of candidal cystitis is based on a urine sample culture growth of more than 10,000 colonies/ml. Initial treatment involves removing as many of the precipitating factors as possible. The current treatment of choice is irrigation of the bladder with amphotericin B. Continuous irrigation with a three-way catheter is recommended over intermittent instillations. Oral flucytosine can be added to exert synergistic action in persistent infections, or when renal infection is suspected, or if catheterization is not desirable. The major problem with flucytosine is that many strains of Candida are initially resistant, and some strains may develop secondary resistance during the course of therapy. Because of its potential for toxicity, intravenous amphotericin B is reserved for systemic infections and for those infections refractory to more conservative therapy.

Collaborative clinical pharmacokinetic services.

A program for routine pharmacokinetic interpretation of serum analyses of gentamicin, tobramycin, amikacin, phenytoin, phenobarbital, theophylline, lidocaine, digoxin, quinidine, and procainamide at the Medical University of South Carolina Hospital is described. Results of all analyses of serum for the drugs listed are evaluated by a pharmacist trained in clinical pharmacokinetics. Patient variables relevant to the determination of drug serum concentrations, drug elimination, distribution, and dosage are given appropriate consideration in each evaluation. A summary of the pharmacokinetic interpretation and any necessary modification of drug dosage regimens are then written into the progress notes of the patients' medical records. Approximately 12 patients and 20 drug concentrations are evaluated each day. The average charge for te service is +35. This service, which is reimbursed by third-party carriers, has resulted in improved use of laboratory personnel, equipment, and time and has provided a framework for education and research as well as a mechanism for direct contributions to patient care by the pharmacist.

Gentamicin-induced ototoxicity in a carefully monitored renal-failure patient.

A case of gentamicin-induced ototoxicity, documented by electronystagmography and audiometry, in a patient with chronic renal failure is presented. A 39-year-old white man was hospitalized for a renal transplant procedure. Multiple postoperative complications included infection, and the transplanted kidney was rejected eventually. The patient was carefully monitored with frequent serum gentamicin determinations and subsequent pharmacokinetic analysis throughout the six-week course of therapy. Ototoxicity became apparent 10 days after the discontinuance of gentamicin therapy even though predicted and measured levels never fell outside the range of 1.5 to 6.0 microgram/ml throughout the period of antibiotic administration. A brief review of the presentation of gentamicin ototoxicity with special emphasis on the renal-failure patient is included. Clinicians should be aware of potential toxicities and must be able to recognize those patients at high risk. Patients must be monitored carefully, and a risk-benefit analysis should precede proposed therapy.

Evaluation of two lithium carbonate formulations.

An open, two-way crossover study of Latin-square design was used to compare the bioavailability of a new capsular formulation of lithium carbonate, Pfi-Lithium (Pfipharmecs Division, Pfizer, Inc.), with that of standard capsular formulation, Eskalith (Smith Kline & French Laboratories). Eighteen healthy, adult male volunteers received both formulations in a randomly determined order. After administration of each 300-mg dose of lithium carbonate, serial blood specimens were obtained. Data obtained from these specimens were subjected to pharmacokinetic evaluation. There were no significant differences (p less than 0.05) in peak plasma concentration, time to peak plasma concentration, and area under the plasma concentration-time curve. These single-dose suggested that the two formulations were bioequivalent.

Pharmacy in family practice: a description and evaluation.

Expanded pharmacy functions within a private practice setting are described. These activities are a component of a pharmacy training program. The medical practitioners evaluated the program, eliciting an overall positive response. Additionally, future services were priority rated by the staff, demonstrating more accessibility to the services, patient education, and chronic disease care programs as the most desirable projects. As the Clinic and the medical residency expand, the activities of the clinical pharmacist shall continue to develop.