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A survey of drug-related admissions of patients aged 50 years and older was conducted at the Health Sciences Centre, Winnipeg to determine the interrelationship of risk factors, and isolate the effect of age. All nonelective medical admissions were prospectively assessed to determine the role of drug therapy as a contributory factor. Of the 863 eligible admissions, 162 exhibited at least one drug-related adverse patient event (DRAPE) at the time of hospitalization. This accounted for 19% of the admissions (23% of 718 admissions that involved prescription drugs). Although adverse drug reactions were responsible for many DRAPEs (48%), intentional noncompliance (27%), treatment failure (19%), alcohol (14%), and medication error (10%) were also frequent contributing causes. Drugs commonly implicated in DRAPEs were systemic steroids, digoxin, nonsteroidal anti-inflammatory agents, alpha-methyldopa, calcium channel blockers, beta-blockers, theophylline, furosemide, sympathomimetics, thiazides, and benzodiazepines. The risk of a DRAPE was related to the number of diseases prior to admission (r = 0.81; P less than .026) and the number of drugs used (r = 0.77; P less than .001). Age was not correlated with the risk of a DRAPE. Females had significantly more adverse drug reactions, although sex was not a predictor for overall DRAPE risk.

The kinetic disposition of morphine was compared in 13 young and 7 older healthy subjects after a single intravenous dose of 10 mg/70 kg morphine. The apparent volume of distribution at steady state in elderly subjects was only half of that in young subjects. This difference was derived from reductions in both central and peripheral kinetic compartment volumes in the older subjects. The beta elimination phase for morphine was more rapid, but its plasma clearance was reduced in older subjects. Calculation of the peripheral compartment morphine concentration for these subjects indicated that drug concentration in this kinetic space was higher in older subjects for 1.5 hr after dosing.

Plasma theophylline concentrations were measured after single intravenous infusions of aminophylline to asthmatic patients and normal volunteers. Using two-compartment kinetic analysis, no basic differences in drug disposition were found. For the 16 subiects studied the overall mean plasma clearance rate was 0.0719 I per kilogram per hour, and overall mean beta or slow disposition constant was 0.159 hr-', corresponding to a plasma half-time of 4.36 hr. This information should be useful in determining precise dosage requirements for theophylline in clinical situations.

Many therapeutic agents can be applied more predictably and effectively if a constant plasma concentration is maintained. With the use of the two‐compartment open‐system model, a general and practical method of combining intravenous bolus and continuous infusion is described. The fastest approach to the plateau situation is shown to result from setting the maintenance infusion rate equal to β times the initial bolus, where β is the slower disposition constant. This procedure was verified in 3 normal subiects. Single bolus doses of theophylline were administered to study the pharmacokinetic behavior of this drug in each individual. This information was used to calculate the regimen required to reach a predetermined plateau concentration. The selected bolus and continuous infusion were given, and in each case resulted in constant plasma values within the first hour.

The plasma concentrations and urinary excretion rates of salicylic acid (SA) and some of its metabolites (salicyluric acid [SUA] and acyl and phenolic glucuronide conjugates) were measured after an oral dose of acetylsalicylic acid to 44 healthy subjects of both sexes 20 to 78 years old. There was no change in the SA absorption rate, and plasma clearance of SA was not affected by age or sex. The volume of distribution increased with age in men but not in women. Plasma concentrations of SUA rose with age as the renal clearance of this metabolite fell. The kinetic parameters Km and Vmax for the SA-to-SUA reaction did not change with age; Vmax was significantly higher in women than in men. Urinary recovery of SA and its metabolites essentially accounted for the administered dose, and was little influenced by age or sex. We conclude that these factors play a minor role in the disposition of salicylate.

To determine bioavailability of theophylline in a newOral theophylline preparations continue to be suspect by many physicians because of apparent ineffectiveness or frequent patient intoleranceY Although it has been suggested that most formulations do not yield therapeutic drug concentrations, there are few studies that provide evidence on this assertion. Truitt14 has pOinted out that intravenous theophylline may serve as a standard against which the availability and activity of oral theophylline can be compared. A new formulation, Theograd, ' " has been developed in an attempt to establish sustained release of theophylline after oral ingestion. Each tablet contains 350 mg of theophylline in an inert matrix that allows gradual release and absorption of theophylline from the gut. In our study,

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