Annals of Pharmacotherapy

Intrasubject variability in the systemic clearance of a drug from one treatment to the next in a randomized crossover bioavailability study reduces the ability to differentiate dosage forms with respect to the extent or relative extent of drug absorption. The most commonly used method to reduce this intrasubject variability is a half-life correction first proposed in 1967. The mathematical basis of the half-life correction is reviewed, and it is shown that this correction requires the implicit assumptions that the change in half-life from one treatment to the next quantitatively reflects the change in systemic clearance and that there is no change in apparent volume of distribution. The limitations of this assumption are considered. It is concluded that the half-life correction should be evaluated in all cases where the variability in half-life is random, and applied if it results in a significant decrease in the standard deviation associated with the average measure of bioavailability. On the other hand, if there is a significant difference or strong indication of a difference in half-life between treatments, the half-life correction should not be applied, for it can lead to misinterpretation. Examples illustrating this problem are presented.

A pilot study to test the effectiveness of medication instruction was carried out using 61 voluntary participants age 65 and older. They were interviewed regarding their medication taking, and instruction was individualized using one of four teaching modes: oral; written; oral and written; and oral and written combined with memory aids. Postinstruction interviews revealed no significant difference in compliance among all groups. The preinstruction mean compliance score of all subjects was 98.8 percent. Although compliance, judged specifically on the basis of the prescription label instructions, was extremely high both before and after instruction, drug-taking behavior and knowledge did change. The preinstruction compliance score does not necessarily reflect safe or desirable drug-taking behavior. There was no specific information given to clients with their prescriptions and prescription medications, indicating, for drug-therapy decision makers, a much broader problem than noncompliance.

A review of thyrotoxic storm is presented. Included are causes, symptomatology, and mortality rates. Special emphasis is placed on the strong correlation between adrenergic blockade and success rates in treating thyrotoxic storm. Pharmacotherapy of the acute storm patient is discussed in detail with respect to agents that (1) decrease production of thyroid hormones; (2) block release of preformed thyroid hormones from the gland; (3) blunt the effects of excess thyroid hormones on the various target organs (e.g., CNS and heart); and (4) serve to decrease the metabolic strain on all organ systems caused by thyrotoxic storm.

The freezing of antibiotic admixtures has been proposed as a potentially useful method by which the efficiency of admixture services might be improved. The time involved in thawing, however. has discouraged the implementation of this practice. This study describes a technique of thawing frozen antibiotic admixtures contained in minibags in commercially available microwave ovens. A quantitative microbiological agar gel diffusion assay was employed to determine the effect of such treatment on the antibiotic activity of the admixture. Admixtures containing cephalothin sodium, cefazolin sodium, cefamandole nafate, cefoxitin sodium, penicillin G potassium, ampicillin sodium, oxacillin sodium, carbenicillin disodium, and gentamicin sulfate in dextrose 5% solution were frozen at — 20°C for 30 days. The admixtures were assayed immediately before freezing, and again after either thawing technique: that is, upon exposure of the minibags to room temperature air or to microwave radiation. Assays were also performed 8 and 24 hours after thawing in order to assess antibiotic stability following each freeze-thaw treatment.

It was discovered that, with the exception of ampicillin sodium, each of the antibiotics studied could be frozen and thawed as described without significant loss of activity, and were stable for 24 hours after thawing.

The application of a freeze microwave-thaw technique to central admixture services can be seen as a cost-effective method of circumventing many of the problems associated with existing programs.

A case describing possible acetazolamide-induced metabolic acidosis is reported. The importance of recognizing unusual complaints of abdominal pain, anorexia, headache, and sensorium changes in elderly patients receiving acetazolamide is emphasized. Differential diagnosis of metabolic acidosis is also discussed.

The blood pressure of a 36-year-old male with malignant hypertension could not be controlled adequately by as many as eight concurrent oral and parenteral antihypertensive agents administered over a three-week period. These agents included the potent vasodilating agent minoxidil. Only after the initiation of captopril, an oral angiotensin converting enzyme inhibitor, was his blood pressure normalized.