Effect of thioridazine on phenytoin serum concentration: a retrospective study.

Serum phenytoin concentrations before and after the addition of thioridazine were retrospectively compared in 27 adults to determine if an interaction occurred between these two drugs. A change in the serum phenytoin concentration of +/- 4 micrograms/ml was considered clinically significant; by this definition four patients (14.8 percent) had an increase, two (7.4 percent) had a decrease, and most (77.8 percent) demonstrated no change. The mean difference was 0.8 microgram/ml +/- 3.7 micrograms/ml and was not found to be statistically significant (p less than 0.1). Clinically important alterations in phenytoin serum concentration as caused by thioridazine appear to be infrequent.

Clinical pharmacy services in Florida hospitals--1984.

To ascertain the progress made in the implementation of clinical services in Florida hospitals, a survey conducted in 1977 was readministered in 1984. Questionnaires were sent to the directors of pharmaceutical services of all 256 Florida hospitals. Nine questions on clinical services were identical to the 1977 survey and two additional questions were included on nutritional support services and pharmacokinetic dosing consultations. The directors were also asked if they had conducted studies to document the cost-effectiveness of their clinical pharmacy services. Questionnaires were returned by 75% of the directors. As in the 1977 survey, approximately half of the hospitals had less than 200 beds. Slightly more than 82% of the hospitals had total unit dose systems and about 7% had partial systems, which was considerably higher than the 58% with either total or partial systems found in the 1977 survey. Services such as patient monitoring, inservice education, and drug-use review were being offered substantially more than in 1977. Conducting patient medication histories, attending rounds with physicians, and providing discharge consultations were the least-performed clinical services. The reasons given for not implementing these services were similar in both surveys. However, while the lack of adequately trained pharmacists was frequently cited in 1977, very few respondents cited it as an obstacle in 1984. Several respondents indicated that they had documented cost savings attributable to their clinical pharmacy services. Clinical pharmacy programs are continuing to grow in Florida hospitals; however, pharmacy administrators appear to be having some of the same problems implementing these services as they did previously.

Comparison of eight phenytoin dosing methods in institutionalized patients.

Until now, no evaluation of phenytoin dosing methods has been undertaken in a large group of patients, to our knowledge. The goal of this study was to determine which of eight different dosing methods most accurately predicts a phenytoin steady-state concentration. Seventy-six patients were chosen, retrospectively, from a state-funded institution for the mentally retarded. Eligibility criteria included two or more different doses of phenytoin and corresponding plasma concentrations. Relative predictive performance was determined by comparing results of simple linear regression. Also, relative bias and precision were determined by comparing mean prediction errors, root mean squared errors, and respective 95% confidence intervals. Of the methods requiring one dose-concentration pair, Rambeck's nomogram was the best predictor of phenytoin concentrations. The methods requiring two known doses and plasma concentrations were more accurate. Their predictive performance was equivalent, although use of the Tozer equation might be preferred for its convenience. None of the methods tested were sufficiently precise to substitute for confirmatory serum phenytoin concentrations.

Drug-related admissions to a Veterans' Administration psychiatric unit.

Forty-one consecutive admissions to an inpatient psychiatric service were monitored prospectively for drug-related problems. During the four-month study, 22 (54 percent) of the admissions were determined to be drug-related; in 12 (29 percent) admissions, a drug-related problem was identified as the primary cause of hospitalization. Significant differences were found in the length of hospitalization, age, and race when the group with drug-related problems was compared with a group with non-drug-related problems.

Effect of cimetidine on phenytoin serum levels.

Cimetidine, 300 mg p.o. four times a day, was administered for 5 days to nine epileptics who were stabilized while receiving phenytoin. Five patients had statistically significant increases in phenytoin serum levels, including two who became clinically toxic. One patient had a statistically significant decrease in phenytoin serum concentration. A relationship was not found between cimetidine levels and change in phenytoin serum levels. Cimetidine can cause significant changes in phenytoin serum levels which may be manifested clinically.

Rapid infusion of phenytoin sodium loading doses.

The use of rapid intravenous infusions of phenytoin sodium to achieve prompt plasma therapeutic concentrations of phenytoin was studied in adult epileptic patients. Six adult patients who experienced recent tonic-clonic seizures were selected for study. Four of them had not been treated with phenytoin before the study; two were on chronic phenytoin therapy but had subtherapeutic serum levels. A leading dose of phenytoin sodium (15 mg/kg in 100 ml of 0.9% sodium chloride injection) was infused at 30-50 mg/min. Blood samples were drawn before phenytoin administration, every five minutes during the infusion, and at 1, 2, 4, 8, 12, 18, and 24 hours after completion of the infusion. Adverse effects were monitored during the infusion. Pharmacokinetic variables were calculated. Patients received from 750 to 1500 mg phenytoin sodium (mean +/- S.D. = 1040.8 +/- 297.3 mg). From 5 to 30 minutes were required to reach therapeutic (10-20 micrograms/ml) serum phenytoin concentrations; concentrations peaked at 31.1 +/- 10.0 micrograms/ml. Four of the six patients had therapeutic serum concentrations at 18 hours after completion of the infusion. Adverse effects were minimal and not severe; no cardiotoxicities were noted. Phenytoin half-life was 31.2 +/- 8.4 hours, total plasma clearance was 47.2 +/- 10.7 ml/kg/hr, and volume of distribution was 1.96 +/- 0.46 liters/kg. It is concluded that rapid intravenous infusion of phenytoin appears to be a reasonably safe and effective method of rapidly reaching therapeutic phenytoin concentrations.

Parenteral nutrition utilization: evaluation of an educational protocol and consult service.

A two part study was undertaken to evaluate the effectiveness of an educational protocol and consult service on parenteral nutrition (PN) utilization. Forty-one patient admissions were evaluated retrospectively and nine prospectively. Average length of hospital stay and number of days on PN were decreased significantly (p less than .05). Frequency of adverse effects were also decreased significantly (p less than .05). A positive trend toward selection of patients for enteral rather than PN was evidenced. Utilization of already available manpower and financial resources by this modified approach should contribute toward reducing costs and hazards of PN therapy, particularly for smaller hospitals with both limited requirements and resources, as well as for teaching institutions.