Sources of prediction error when using a Bayesian method to evaluate nortriptyline serum concentrations.

A Bayesian method was used to evaluate nortriptyline (NTP) serum concentrations (Cps) and predict future Cps in two populations: five simulated groups (n = 20 each) with known clearance (CL) and volume of distribution (Vd), and an actual inpatient group (n = 20). The effects of weight, CL, Vd, and magnitude of Cps on absolute prediction error (APE) were evaluated. In simulated groups, Cps after two doses of NTP and for steady-state were calculated for normal, increased, and decreased Vd and CL. In the actual patient group, Cps were measured in the first few days after starting NTP administration and again during maintenance therapy. The first Cps were used in the Bayesian program to estimate CL and Vd to predict the second Cps. In the simulated group, PE and APE differed significantly between normal and decreased values of CL. A large Vd resulted in less of a change in PE or APE in these subjects, but when combined with low CL led to the largest errors. In the actual patient group, PE was -5.9 +/- 19.2 ng/mL and APE was 15.4 +/- 12.6 ng/mL. In these patients, only body weight was correlated with the percent APE (r = 0.607, P = 0.005). The Bayesian method performs well clinically, but increased Vd and decreased CL can lead to higher PE. Clinically, the only factor that predicted higher APE was obesity. This may reflect an effect on Vd, and in these patients, a high APE may occur.

A multidisciplinary approach to monitoring adverse drug reactions in a long-term care facility.

Use of a drug in any patient requires careful consideration. This is especially true in the elderly patient who may be at risk for adverse drug reactions (ADRs). The drug regimens of patients in long-term care facilities must be reviewed monthly by a pharmacist. The continuous monitoring for ADRs in this setting should be systematized, and the pharmacist is in a unique position to coordinate this effort. This article describes a multidisciplinary approach to monitoring ADRs. By designing a program using the skills of different disciplines, day-to-day continuous monitoring can be accomplished with little increase in time commitment by any one discipline. The approach described provides a systematic basis for monitoring, evaluating and documenting ADRs that has been well accepted by all involved.

Treatment of attention deficit hyperactivity disorder in children.

These are controversial times for those who care for children with attention deficit hyperactivity disorder (ADHD). Class action law suits have been filed in federal courts in California and New Jersey accusing a manufacturer of methylphenidate and the American Psychiatric Association of conspiring to expand the use of this drug. These suits have recently been dismissed. This is just the latest chapter in the long-running debate over the existence, diagnosis, and treatment of ADHD. Controversies relating to ADHD continue to polarize physicians, educators, caregivers, and parents of these children. There are those who believe that ADHD does not exist as a true disorder. At the other end of the spectrum are those who are too quick to make the diagnosis without an adequate patient workup. Parents can unfortunately get caught in the middle of this debate when making treatment decisions for their children.

Health behaviors and pharmacotherapy.

OBJECTIVE: To review factors related to health beliefs and behavior that affect treatment adherence, and to suggest behavioral strategies for improving adherence. DATA SOURCES: We conducted MEDLINE and PSYHLIT (January 1966-October 1997) searches of English-language literature pertaining to behavioral medicine and health behavior as they relate to treatment adherence. Additional articles from these sources and reference texts were identified. DATA EXTRACTION: All articles and chapters identified were considered. The most pertinent information, as judged by the authors, was selected for discussion. DATA SYNTHESIS: Health care is moving into an era of disease management, and practitioners will be called upon to help patients change health-related behaviors and to improve adherence to treatment. Fundamental to this new paradigm of practice is an understanding of behavior, its relationship to health, and methods by which it can be altered. Current concepts of health behavior have been heavily influenced by social learning theory, self-efficacy theory, and a biopsychosocial view of health and disease. The intent of this review is to provide clinicians with an overview of factors that affect health-related behaviors, as well as suggestions for helping patients to improve them. As illustrations, behavioral interventions used in patients with asthma are presented. CONCLUSIONS: Adherence to treatment recommendations depends on a complex interplay of many psychological variables. An understanding of these factors, and how behavioral techniques may be used, will help healthcare providers to assist patients in improving adherence.

Maintenance requirements of L-thyroxine in the treatment of hypothyroidism.

By analyzing data from 68 hypothyroid patients ranging in age from 15 to 75 years who had been maintained in a euthyroid state for at least a year with oral levothyroxine sodium therapy, we attempted to determine whether there was a correlation between L-thyroxine dose and body weight or patient age. The mean replacement dose of L-thyroxine was 186 mug a day +/-69.6 or 2.76 mug per kg of body weight a day +/-0.82. There was a significant correlation between L-thyroxine dose and body weight (P<.001), but due to the small number of patients studied who were older than 65 years of age, no correlation was noted between L-thyroxine dose and age.

Nine-year experience with a pharmacist-managed anticoagulation clinic.

A pharmacist-managed anticoagulation clinic is described, and information on patient outcome during a nine-year period is presented. Since 1974, a pharmacist has managed an anticoagulation clinic for ambulatory patients and inpatients at San Francisco General Hospital Medical Center. The pharmacist's primary responsibilities include the following: educating patients about their diseases and the importance of drug therapy, monitoring patients' vital signs, performing physical examinations, and adjusting warfarin dosage to maintain prothrombin times within the therapeutic range (1.7-2.5 times normal using control values of 1.0-1.2). These patients are also under the care of their primary physicians. The pharmacist's work is checked by the chief of the cardiac clinic at the end of each clinic session. The effectiveness of the pharmacist in managing clinic patients is reviewed periodically; from January 1975 through June 1984, the pharmacist had treated 140 patients (141 courses of therapy). Of 1792 prothrombin times taken during this time, 1060 (59.2%) were within the therapeutic range of 17-25 seconds, 510 (28.5%) were less than 17 seconds, and 222 (12.4%) were greater than 25 seconds. Only four major hemorrhagic events (0.002 hemorrhages per patient-treatment month) and 89 minor events (0.05 hemorrhages per patient-treatment month) occurred. The recurrence rate of thromboembolic events was 0.007 per patient-treatment month. Pharmacist-managed warfarin therapy in these clinic patients resulted in a level of anticoagulation control and morbidity that was acceptable to physicians.

Early individualization of tricyclic antidepressant dosing using a Bayesian pharmacokinetic model.

Existing methods to prospectively dose tricyclic antidepressants (TCAs) require either specific test doses, precisely timed serum sampling, or both. We prospectively tested a new pharmacokinetic model that allows flexible dosing and sampling to determine maintenance requirements in patients receiving TCAs. Thirty-four patients entered the study. Drug concentrations were measured on the third day after starting TCA therapy. These values were analyzed using a Bayesian pharmacokinetic model to determine drug clearance and volume of distribution. This information was then used to predict the serum concentration resulting from a maintenance dose chosen by the psychiatrist. In phase I (n = 17), patients received imipramine without specific starting doses. Phase II (n = 17) was performed to provide a preliminary evaluation of the method in the usual clinical environment. In this phase, patients received either amitriptyline, imipramine, desipramine, doxepin (75 mg on day 1,100 mg on day 2), or nortriptyline (50 mg on day 1, 75 mg on day 2). Lower doses were allowed if clinically indicated. The predictability of future serum concentrations was then compared between the two phases. The mean prediction errors (model bias) in phases I and II were -15.5 +/- 27.3 and -12.3 +/- 21.8 ng/mL and were not different (p greater than 0.05). The absolute prediction errors (model precision) were 18.5 +/- 25.1 and 18.8 +/- 16.0 ng/mL and were not different (p greater than 0.05). Two slow metabolizers were identified (clearance less than 0.10 L/kg/h). This new method allows the determination of maintenance dose requirements early in therapy without standard test doses or specifically timed serum sampling.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of ranitidine on theophylline metabolism in healthy Koreans living in China.

OBJECTIVE: To evaluate the effect of concurrent ranitidine therapy on theophylline metabolism in healthy Koreans. DESIGN: A 4-week, double-blind, randomized, placebo-controlled, crossover study. SETTING: The Clinical Research Unit, Department of Pharmaceutical Sciences, Yanbian Medical College, Yanji, China. SUBJECTS: Six young, healthy, nonsmoking Korean volunteers residing in China with no known factors that would alter theophylline metabolism. INTERVENTIONS: Subjects received extended-release oral theophylline at a constant dosage over 4 weeks to yield a serum concentration (Cp) between 5 and 10 micrograms/mL. Week 1 was the dosage titration phase. During week 2 subjects randomly received either ranitidine or a matching placebo. Week 3 was a washout phase, and during week 4 subjects were crossed over to receive either placebo or ranitidine. At the end of each treatment week, serum and urinary metabolite concentrations were measured. OUTCOME MEASURES: Theophylline serum concentrations and urinary concentrations of 1-methylxanthine, 1-methyluric acid, 3-methylxanthine, and 1,3-dimethyluric acid were measured. Estimates of clearance (Cl), volume of distribution (Vd), and half-life (t1/2) were determined. RESULTS: Concurrent administration of ranitidine with theophylline did not significantly alter theophylline Cp, Cl, Vd, or t1/2. Urinary concentrations of major theophylline metabolites also were not changed. CONCLUSIONS: Ranitidine does not significantly alter the metabolism of theophylline in healthy Koreans residing in China.