A double-blind, placebo-controlled study of acetylsalicylic acid (ASA) in trained runners.

Acetylsalicylic acid (ASA) is a short-acting oral inhibitor of the cyclooxygenase enzyme. Ingestion of ASA is associated with a decrease in prostaglandins, including those of the E2 series, as well as prostacyclin, and thromboxane. Consumption of therapeutic doses is associated with decreased pain and inflammation and is therefore used in a variety of inflammatory conditions. Platelet aggregation is also inhibited. Because of these observations, and the fact that platelet aggregation has been noted to be altered during exercise, the effects of ASA on exercise tolerance was of interest. We studied 17 healthy male volunteers who regularly ran as a source of exercise. During the study they ingested either 650 mg of ASA or placebo 30 min before running 2 miles (3.2 km). Outcome of the double-blind crossover study was measured by the time required to run a 2-mile distance. No differences between ASA or placebo were noted in the subjects. These data suggest that 650 mg of ASA as a premedication has little effect on exercise performance in normal endurance runners. However, whether ASA may affect pain after exercise or whether other dosage intervals would be more beneficial needs further study.

Multidisciplinary program for detecting and evaluating adverse drug reactions.

An adverse drug reaction (ADR)-reporting program involving detection of charted ADRs by quality assurance nurses and data collection and causality assessment by staff pharmacists is described. The voluntary ADR-reporting mechanism used in a 900-bed, university-based hospital complex produced less than one ADR report per month. The newly implemented system depends on nurses to detect and report documented ADRs through concurrent chart review. Staff pharmacists are then responsible for follow-up chart review, data collection, and causality assignment based on two published algorithms. An inservice education program designed to increase the awareness and understanding of ADRs was provided to the department of pharmacy and the quality assurance nurses. The clinical staff provides quality assurance through weekly ADR committee meetings. Drug information center personnel complete the causality algorithms by using the data collected by the staff pharmacists. The ADR committee then compares the algorithm results of the two assessors. Discrepancies in scoring are evaluated to determine whether a change in the system is necessary. An FDA report is generated if the staff pharmacist assessor and the drug information center assessor obtain results of "probable" for both algorithms. An ADR-reporting program that relies on quality assurance nurses to detect charted ADRs and on staff pharmacists to evaluate reported ADRs increased the average number of ADRs reported from 0.4 to 20 per month.

A utilization review of theophylline assays: sampling patterns and use.

Use of the theophylline assay was reviewed for two months in 121 hospital inpatients who received 426 evaluations at a university medical center. Clinicians adapted published audit criteria for the collection and use of theophylline assays. The charts of all patients receiving theophylline were examined daily, and the following data, among others, were collected: pulmonary function tests, arterial blood gases, liver function tests, vital signs, and physician assessments. Only 29.8 percent of the evaluations complied with all criteria. When the audit categories of rational indication, correct performance, and appropriate dosage adjustment were evaluated independently, compliance rates were 69.1, 72.3, and 67.2 percent, respectively. In 171 cases (48.6 percent), the physicians' instructions for the assay were inadequate to ensure proper collection time by the phlebotomist. Hospital laboratory charges for unnecessary, incorrectly performed, or inappropriately used theophylline assays were estimated to exceed +77000 annually. This audit demonstrates the need for a collaborative pharmacokinetics service with reimbursement through the physician billing charge.

A utilization review of digoxin assays: sampling patterns and use.

A review of digoxin assay utilization concurrent with patient hospitalization was conducted at the University of Texas Medical Branch. An interdepartmental committee of clinicians adapted audit criteria for the collection and use of digoxin assays. This included rational indications, correct performance (i.e., collection and processing of serum sample) and appropriate dose adjustment. The charts of all patients receiving digoxin were examined daily, whether or not the physician had ordered a drug assay. Contributory data were collected and analyzed, including serum electrolyte concentrations, arterial blood gases, renal function tests, vital signs, physician assessments, and other information relating to pertinent and concomitant diseases or drug therapy. The 2-month review included 104 hospital inpatients who received 245 evaluations. Only 38.4% of the evaluations were determined to be compliant with all criteria. When the audit categories of rational indication, correct performance, and appropriate dosage adjustment were evaluated independently, compliance rates were 66%, 73% and 86%, respectively. In 108 cases (52%), the physicians provided inadequate instructions in their request for the digoxin assay to insure proper collection time by the phlebotomist. Approximately 94% of all assay results were verbally communicated to the physician or returned to the patients' charts for use in patient management within a minimum of 24 hours. Hospital laboratory charges for unnecessary, incorrectly performed, or inappropriately used digoxin assays were estimated to exceed $100,900 annually. The audit was used to demonstrate the need for changes in hospital procedures and house staff training. A collaborative pharmacokinetics service was organized with reimbursement accomplished through the physician billing charge.

Effect of antacid on bioavailability of theophylline from rapid and timed-release drug products.

Magnesium aluminum hydroxide suspension (an antacid) was given concurrently with either theophylline anhydrous tablets or theophylline anhydrous timed-release capsules to 13 volunteers using a four-way crossover design. Serum theophylline was measured by reversed-phase high-pressure liquid chromatography. The serum level-time curves were individually fitted to an oral absorption one-compartment open model. The pharmacokinetic parameters (mean +/- SD) KA, K, AUC, and F/V for theophylline from the rapid release theophylline anhydrous tablets were 2.1 +/- 1.3 hr-1, 0.15 +/- 0.06 hr-1, 89.2 +/0 39 microgram hr/ml, and 0.0023 +/- 0.002 kg/ml, respectively; from the anhydrous timed-release capsules, they were 0.27 +/- 0.08 hr-1, 0.20 +/- 0.07 hr-1, 79.0 +/- 27 microgram hr/ml, and 0.0030 +/- 0.007 kg/ml, respectively. The concurrent administration of 15 ml of antacid (magnesium aluminum hydroxide suspension) with the theophylline products did not significantly affect any of these pharmacokinetic parameters. The extent of theophylline bioavailability from all drug products was consistent and similar as shown by the F/V and AUC values.