A primer on drug utilization review.

Many health care organizations evaluate drug utilization to improve the quality of patient care, reduce pharmaceutical expenditures, and enhance therapeutic outcomes. The Drug Regimen Review, instituted in 1974 as part of a quality assurance program for the care of Medicaid recipients, has reduced medication use, medication errors, adverse drug reactions, and drug-drug interactions. The Drug Usage Evaluation, a sophisticated analysis of drugs, their uses, and their contributions to various patient outcomes, is performed by member institutions of the Joint Commission on Accreditation of Healthcare Organizations. The 1990 Omnibus Budget Reconciliation Act (OBRA '90) established the Drug Utilization Review (DUR), which was implemented by state Medicaid outpatient prescription programs in 1993. Pharmacists performing DURs must review past patterns of drug misuse, monitor current therapy, and offer patient counseling. Drug utilization reviews have reduced inappropriate drug use and decreased drug costs.

Effects of aspirin and ibuprofen on the pharmacokinetics and pharmacodynamics of glyburide in healthy subjects.

OBJECTIVE: To determine the effects of aspirin and ibuprofen on the pharmacokinetics and pharmacodynamics of glyburide in healthy volunteers. DESIGN: Single-center, randomized, two-way, crossover design following an initial baseline evaluation phase. SETTING: Outpatient, university-based ambulatory care facility. PATIENTS: Sixteen healthy nonsmoking men aged 20-34 years. INTERVENTION: Three phases consisting of six treatments. Phase 1 began with treatment A, a baseline oral glucose tolerance test (GTT), followed by treatment B, glyburide 5 mg plus a GTT. The other two phases were administered in a crossover design. Phase 2 consisted of the administration of aspirin 975 mg qid for 4 days. On day 3 a GTT was administered (treatment C) and on day 4 glyburide 5 mg plus a GTT was administered (treatment E). Phase 3 consisted of the administration of ibuprofen 600 mg qid for 4 days with a GTT on day 3 (treatment D) and glyburide 5 mg plus a GTT on day 4 (treatment F). MAIN OUTCOME MEASURES: Serum glyburide concentrations after each treatment, as well as glucose and insulin, ibuprofen, and salicylate serum concentrations and glyburide free fractions. RESULTS: Aspirin administration resulted in an 85% increase in mean total glyburide oral clearance and a 29% increase in glyburide free fraction. Ibuprofen administration resulted in a slight increase in mean glyburide free fraction, but no significant changes in glyburide pharmacokinetic parameters were observed. Insulin concentrations were increased during the glyburide plus aspirin treatment. Conflicting results were observed in the glucose parameters. CONCLUSIONS: The potential for this glyburide-aspirin interaction resulting in a transient hypoglycemia should be considered in diabetic patients receiving glyburide therapy.

Pharmacokinetics and pharmacodynamics of glyburide in young and elderly nondiabetic adults.

The pharmacokinetics and pharmacodynamics of glyburide were studied in elderly and young nondiabetic adults. Healthy nondiabetic men and women 18-40 years of age (young subjects) and 60-85 years of age (elderly subjects) were recruited. After an overnight fast, the subjects were given a baseline glucose tolerance test (GTT). The next day, again after a fast, each subject was given a 5-mg oral tablet of glyburide, and the GTT was performed one hour later. Serum glucose, serum insulin, and plasma glyburide concentrations were determined. Twenty elderly (mean +/- S.D. age, 65.7 +/- 5.3 years) male (n = 10) and female (n = 10) volunteers and 15 young (22.3 +/- 4.5 years) male volunteers were enrolled. Compared with the young subjects, the elderly subjects had slower glyburide absorption, as determined from a lower peak plasma concentration and smaller area under the plasma concentration-time curve from zero to four hours (AUC0-4). The elderly subjects also had a lower glyburide elimination rate constant and higher volume of distribution and a 52% higher free fraction. There was no difference in the glyburide AUC0-24 or AUC0-infinity or in oral clearance between the groups. The elderly group had greater increases in serum glucose and insulin concentrations after the baseline GTT. After glyburide administration, the elderly group had a smaller fractional decrease in the glucose AUC0-3 from the baseline GTT result than the young subjects. Linear regression analysis of the relationship between the fractional change in glucose concentration and the glyburide AUC0-4 showed significantly different slopes between the two groups. The aging process appears to affect the pharmacokinetics and pharmacodynamics of glyburide.

The paradoxical effect of cimetidine and ranitidine on glibenclamide pharmacokinetics and pharmacodynamics.

The potential interactions between H2-receptor antagonists, cimetidine and ranitidine, and glibenclamide were studied in 15 non-smoking male volunteers. The study consisted of six treatment phases. Treatment A (3 h oral glucose tolerance test) consisted of 75 g dextrose in 300 ml carbonated water. Treatment B consisted of one 5 mg tablet of glibenclamide in addition to a glucose tolerance test. Treatment C, cimetidine 300 mg orally four times daily for 4 days and Treatment D, ranitidine 150 mg orally twice daily for 4 days were administered in a randomized, crossover fashion. On day 3 of Treatments C and D, subjects received an oral glucose tolerance test. On day 4 of Treatments C and D, subjects received 5 mg of glibenclamide in addition to cimetidine (Treatment E) or ranitidine (Treatment F) and an oral glucose tolerance test. Compared with the control treatment, cimetidine increased the glibenclamide AUC (973 vs 710 ng ml-1 h), but during ranitidine dosing glibenclamide AUC (726 ng ml-1 h) was not significantly different from the control. Apparent oral glibenclamide clearance decreased from 8.25 l h-1 under the control treatment to 6.0 l h-1 following cimetidine but was unchanged during ranitidine (7.97 l h-1). Plasma glucose concentrations were unexpectedly higher when glibenclamide was administered with cimetidine or ranitidine (glucose AUC 237 mg dl-1 h, 228 mg dl-1 h) when compared with glibenclamide administered alone (195 mg dl-1 h, P less than 0.0001). Plasma insulin concentrations were significantly elevated when H2-receptor antagonists and glibenclamide were administered concurrently.(ABSTRACT TRUNCATED AT 250 WORDS)

Attitudes of patients with hypertension or arthritis toward the frequency of medication administration.

The attitudes of patients with a nonpainful chronic illness (hypertension) and the attitudes of patients with a painful chronic illness (arthritis) toward the frequency of medication administration were compared. Hospitalized patients with rheumatoid arthritis (n = 83) and hypertension (n = 117) were interviewed by study monitors. Multiple-daily dosing was preferred by 70% of the arthritis patients and 61% of the hypertension patients for pain medications. The majority of patients in both groups preferred single-daily dosing for nonpainful conditions. The majority of patients in both groups believed that there was no difference between the dosing regimens in terms of the number of side effects. Thirty-five percent of the patients with arthritis and 19% of the patients with hypertension stated that they would consider increasing or decreasing the number of daily doses of their medication. A single daily dose might not be the optimal dosing regimen for all medications for all patients. Clinicians should consider the nature of the patient's illness and its potential influence on compliance when selecting a dosing regimen.

Intravenous ampicillin pharmacokinetics in the third trimester of pregnancy.

The pharmacokinetics of a single dose of intravenous ampicillin were studied in nine patients during their third trimester of pregnancy. Each volunteer was given either 500 mg (5.7-8.8 mg/kg) or 1 g (15.4-21.4 mg/kg) of sodium ampicillin by rapid infusion. Postinfusion plasma concentration-time curves followed biexponential decay in all subjects. Calculated parameters included a mean plasma distribution volume of 177.1 +/- 97.5 ml/kg, tissue or peripheral distribution volume of 246.2 +/- 143.9 ml/kg, elimination half-life of 1.60 +/- 0.51 h, and total body clearance of 4.59 +/- 1.48 ml/min/kg. Dose-dependent disposition was not observed. Gestation-specific drug therapy research during pregnancy is discussed.