To rationalise medication in the elderly, physicians often change multiple dose regimens to once daily in the belief that this improves compliance. Effective methods for measuring compliance have only come into use during the last decade. Partly as a result of this, high quality studies comparing once daily with other regimens in the elderly, are lacking. What evidence there is, from investigations which used suboptimum methods and/or mixed (elderly/younger) patient groups, does not justify the widely held view that ‘once a day is best’, particularly when compared with twice daily regimens.

Given the current emphasis on the "concordance" prescribing model, a study was designed to determine the influence of patients' beliefs about epilepsy, beliefs about medication and a range of neuroepilepsy variables on drug adherence among a sample of epilepsy patients. A special feature of the study was the use of a credible objective measure of drug adherence. Psychological health was also assessed. Thirty-seven patients were recruited from a local epilepsy clinic. Beliefs about epilepsy (illness representations), beliefs about epilepsy medication, anxiety, depression, neuroepilepsy status and adherence were all measured. Data were collected via clinical interview and questionnaire methods. Adherence with drug treatment was determined by an objective measure using low-dose phenobarbital as an indicator of adherence and, or, measurement of antiepileptic drug levels. Neither illness representations nor beliefs about epilepsy drugs were related to adherence. With the exception of time since last seizure, which was positively related to adherence, neuroepilepsy variables were unrelated to adherence. A number of significant associations between cognitive representations of epilepsy and mood were found.

BACKGROUND:The aim of this study was to assess the undertreatment of elderly mild to moderate Alzheimer's disease (AD) patients in the United States utilizing baseline data from a community-based trial that has established comparability to national survey samples on demographic characteristics.METHODS:Baseline data were used from an open-label, 12-week, postapproval study of compliance with galantamine, an AChEI and nicotinic receptor modulator, and vitamin E. A total of 2,114 patients from 406 community-based US practices in which physicians had previously treated patients with acetylcholinesterase inhibitors (AChEIs) were included in the study. This population reflects a large, ethnically diverse patient pool consistent with the demographics of the elderly population in the United States, atypical of those enrolled in most AD trials.RESULTS:The majority of patients (64.5%) were described by either themselves or their caregivers as not having received prior AChEI treatment. Positive associations were found between past AChEI treatment and longer time since diagnosis, white race, higher education, medical care by a neurologist, and older caregivers. The likelihood of having received previous AChEI treatment was higher among white patients (61.9%) than among those from other ethnic groups combined (25.8%).CONCLUSIONS:The similarity of patient demographic characteristics to the 2000 US Census figures for the population aged >65 years makes this data set a potentially powerful tool for planning public health initiatives. Findings suggest that patients with mild to moderate AD are undertreated and that specialist and nonspecialist organizations should discuss and implement ways to optimize management of this disease.

AIMS:There is some evidence that monitoring methadone plasma concentration may be of benefit in dosage adjustment during methadone maintenance therapy for heroin (opiate) dependence. However, the kinetics of oral methadone are incompletely characterized. We attempted to describe the latter using a population approach combining intensive 57 h sampling data from healthy subjects with less intensive sparse 24 h data from opiate users.METHODS:Single oral doses of rac-methadone were given to 13 drug-naive healthy subjects (7 men and 6 women) and 17 opiate users beginning methadone maintenance therapy (13 men and 4 women). Plasma methadone concentrations were measured by h.p.l.c. Kinetic analysis was performed using the P-Pharm software.RESULTS:Comparison of kinetic models incorporating mono- or biexponential disposition functions indicated that the latter best represented the data. The improvement was statistically significant for the data from healthy subjects whether the full 57 h or truncated 24 h profiles were used (P<0.031 and P<0.024, respectively), while it was of borderline significance for the more variable data from opiate users (P=0.057) or for pooled (healthy subjects and opiate users) data (P=0.066). The population mean oral clearance of methadone was 6.9+/-1.5 s.d. l h(-1) (5.3+/-1.2 s.d. l h(-1) using 0-24 h data) in the healthy subjects. The results of separate analyses of the data from opiate users and healthy subjects were in contrast with those obtained from pooled data analysis. The former indicated a significantly lower clearance for opiate users (3.2+/-0.3 s.d. l h(-1), P<0.001); 95% CI for the difference = -3 to -6 l h(-1) and no difference in the population mean values of V/F (212+/-27 s.d. l and 239+/-121 s.d. l, P=0.15), while according to the latter analysis addiction was a covariate for V/F but not for oral clearance. A slower absorption of methadone in opiate users was indicated from the analysis of both pooled and separate data. The median elimination half-life of methadone in healthy subjects was 33-46 h depending on the method used to calculate this parameter.CONCLUSIONS:Estimates of the long terminal elimination half-life of methadone (33-46 h in healthy subjects and, possibly, longer in opiate users) indicated that accurate measurement of this parameter requires a duration of sampling longer than that used in this study. Our analysis also suggested that parameters describing plasma concentrations of methadone after a single oral dose in healthy subjects may not be used for predicting and adjusting dosage in opiate users receiving methadone maintenance therapy unless coupled with feedback concentration monitoring techniques (for example Bayesian forecasting).

Previous studies to identify the pharmacokinetics of R- and S-warfarin have not used steady-state area under the curve (AUC) data during therapeutic doses of racemic warfarin. Instead they have used high single doses of either racemic warfarin or a single enantiomer in volunteers or have taken a single blood sample from anticoagulated patients and assumed full compliance and a steady-state status. In this study, a series of steady-state racemic warfarin, R-warfarin, and S-warfarin serum concentrations, during a 24 h dosage interval, was measured in 10 compliant patients (5 females and 5 males) taking racemic warfarin. The anticoagulation status of all 10 patients according to the International Normalised Ratio (INR) was stable. Their mean (SD) age and weight were 67.0 (9.9) yr and 63.9 (15.4) kg. The mean (SD) clearances derived from steady-state AUC values, following therapeutic dosing, for racemic warfarin, R-warfarin, and S-warfarin were 2.40 (0.82), 2.30 (0.65), and 2.80 (1.17) ml/h/kg, respectively. The mean (SD) ratio of S-warfarin clearance was 1.24 (0.40). Comparison of the clearance measured from the AUC, of these patients, to one point determinations assuming steady state for the samples drawn at either 6, 15, or 20 h after dosage (during the dosing interval) showed some statistical differences. Most single point determinations of warfarin clearance assume that a sample of 12 h postdose is equivalent to that of the steady-state concentration, but in this study the steady-state concentration of only 6 patients occurred between 6 and 15 h postdate. This could explain why these studies demonstrate differences in the clearance of R- and S-warfarin compared to the values we have derived from steady-state AUC data using patients with proven compliance and therapeutic doses.

Incorporation of very low doses of phenobarbital into a methadone linctus has enabled us to monitor the compliance of 7 patients receiving a reducing dose of methadone (detoxification) for treatment for opioid addiction. By measuring both plasma phenobarbital and methadone we detected 4 patients who consumed extra illicitly obtained methadone during the detoxification regime. Treatment outcome was poor; 11 of the original 18 patients dropped out of treatment within 14 days and of those who remained, 4 patients relapsed and reabused illicit drugs and 2 returned to a fixed dose of methadone. Laboratory measurements were successfully used to detect poor methadone compliance.

1. The effect of providing information about medicines by a short 'sales' interview between individual general practitioners and an 'academic representative' on prescribing was investigated. 2. The promotional campaign was designed to encourage a rational approach to prescribing of non-steroidal anti-inflammatory agents in an intervention group of 101 general practitioners selected at random from the Leeds Family Practitioner Committee (FPC). The remaining general practitioners in the Leeds FPC acted as a reference group. 3. The prescribing data for each group for 5 months immediately prior to and 5 months following intervention were compared. 4. Intervention produced a significant increase (P less than 0.005) in the prescribing cost of ibuprofen, the non-steroidal promoted as first choice agent, which was sustained for at least 5 months. 5. Prescribing of the second choice agent, piroxicam, decreased in the reference group but not in the intervention group. 6. There was a decrease in the average prescribing cost of pounds 6.60 per doctor per month in the intervention group compared with the reference group.

A quantitative indicator of compliance is not available for methadone--the drug of choice for the treatment of opioid addiction. We successfully used low-dose phenobarbital (a valid pharmacologic indicator) to measure compliance by incorporating the drug into the methadone medication of patients attending an addiction unit. Plasma phenobarbital and methadone concentrations were measured in 20 (11 clinic-based and 9 community-based) patients receiving long-term treatment with the phenobarbital level-to-dose ratio, together with interviews, to validate methadone measurements and to monitor compliance. Patients attending the unit on a daily basis and who consumed their medication in the clinic were substantially more compliant than community-based patients. Laboratory measurements of phenobarbital and methadone helped to identify the use of illicit methadone, as well as incorrect self-administration, such as the consumption of several days' dosage at one time.

1. A model for predicting the steady-state plasma concentration of phenobarbitone following low-dose phenobarbitone used as an indicator of compliance was derived using data for 10 healthy volunteers. 2. Each volunteer was given a single 30 mg oral dose of phenobarbitone and the pharmacokinetics were described. Subsequently, volunteers were given phenobarbitone 2 mg daily for 28 days and a further pharmacokinetic profile determined during and after this period. 3. An initial predicted estimate of steady-state plasma drug concentration was made using each volunteer's demographic details. This estimate was revised by Bayesian analysis using single timed samples (24, 48, 72 or 96 h) following the single dose. 4. The model was tested on a further 10 healthy volunteers given a single 8 mg dose and who were subsequently given 2 mg daily for 28 days. 5. The revised estimate of peak steady-state plasma phenobarbitone concentration utilising the 96 h post-single dose concentration (356 ng ml-1) was least biased (mean prediction error +/- 95% CI = 10.6 +/- 19.8 ng ml-1) and most precise (root mean square error +/- 95% CI = 28.3 +/- 19.0 ng ml-1). In all cases the peak or trough steady-state drug concentration was within 13% of the predicted value. 6. The model reflected compliance accurately in a further eight volunteers with simulated partial (two-thirds) compliance. 7. The use of a predictive model using Bayesian analysis to estimate expected steady-state plasma phenobarbitone concentrations could increase further the usefulness of low-dose phenobarbitone as an indicator of compliance.

The antihypertensive effects and safety profiles of lisinopril (10 to 40 mg) and atenolol (50 to 100 mg) were compared in a randomized, double-blind, parallel group trial in 144 patients with essential hypertension. After 8 weeks of therapy, seated blood pressure (BP) decreased by 26/15 mm Hg with lisinopril and by 19/14 mm Hg with atenolol. Lisinopril produced a greater reduction (p less than 0.05) in sitting systolic BP than did atenolol. Standing BP decreased by 25/15 mm Hg with lisinopril and by 19/14 mm Hg with atenolol. No important changes in hematologic and biochemical profiles were seen with either drug. Eleven patients, 7 receiving lisinopril and 4 receiving atenolol, were withdrawn because of adverse experiences; another 3 patients defaulted during treatment, 1 in the lisinopril group and 2 in the atenolol group. Both drugs were well-tolerated and are therefore suitable for first-line therapy in essential hypertension.

1. Although, long half-life compounds appear to be more appropriate pharmacological indicators of compliance with treatment, short half-life markers or measurements of short half-life therapeutic drugs are frequently used. 2. We have compared the usefulness of low-dose phenobarbitone (a long half-life indicator), low dose isoniazid (a short half-life marker) and controlled release metoprolol (Metros) (a controlled release formulation of a short half-life 'therapeutic' drug) in seven volunteers with simulated partial (two thirds) compliance. 3. Detection of isoniazid metabolites in urine had an 83% sensitivity and 94% specificity for detecting ingestion within the previous 24 h and 100% sensitivity and 82% specificity for detecting ingestion within the past 6 h but gave no indication of the longer term pattern of compliance. 4. At 28 days (a time when steady-state would be obtained for all three drugs) phenobarbitone plasma levels were 70% (66-76%)--median and interquartile range--of the expected steady-state level if compliance had been complete. Corresponding figures for metoprolol were 82% (37-100%). 5. Measurement of phenobarbitone was much superior to isoniazid or metoprolol measurements in reflecting partial compliance over the previous 1 to 4 weeks.

EEG studies have shown that adult ADHD patients have less stable brain arousal regulation than age and gender matched controls. Psychostimulants have brain arousal stabilising properties evident in EEG patterns. The aim of this study was to investigate whether the stability of brain arousal regulation has prognostic value in predicting response to methylphenidate therapy in adult ADHD patients. In an open-label, single-arm, multi-centre, confirmatory trial, 121 adult ADHD patients were recruited and 112 qualified for the full analysis set. All participants received an initial dose of 20 mg extended release methylphenidate at baseline. After a titration phase of up to 4 weeks, patients remained on a weight-based target dose of extended release methylphenidate for 4 weeks. Using the Vigilance Algorithm Leipzig (VIGALL 2.1), we assessed brain arousal regulation before the treatment with methylphenidate, based on a 15-min EEG at quiet rest recorded at baseline. Using automatic stage-classification of 1 s segments, we computed the mean EEG-vigilance (indexing arousal level) and an arousal stability score (indexing arousal regulation). The primary endpoint was the association between successful therapy, defined by a 30% reduction in CAARS, and stable/unstable brain arousal. 52 patients (46%) showed an unstable brain arousal regulation of which 23% had therapy success. In the stable group, 35% had therapy success, implying an absolute difference of 12 percentage points (95% CI −5 to 29, p = 0.17) in the direction opposite to the hypothesized one. There were no new findings regarding the tolerability and safety of extended release methylphenidate therapy.

Conference Abstract| December 01 1989 Increased Response to Warfarin with Age G Kumar; G Kumar 1University Department of Medicine and Department of Haematology, The General Infirmary, Leeds LS1 3EX Search for other works by this author on: This Site PubMed Google Scholar S Peaker; S Peaker 1University Department of Medicine and Department of Haematology, The General Infirmary, Leeds LS1 3EX Search for other works by this author on: This Site PubMed Google Scholar JA Davies; JA Davies 1University Department of Medicine and Department of Haematology, The General Infirmary, Leeds LS1 3EX Search for other works by this author on: This Site PubMed Google Scholar BE Roberts; BE Roberts 1University Department of Medicine and Department of Haematology, The General Infirmary, Leeds LS1 3EX Search for other works by this author on: This Site PubMed Google Scholar M Feely M Feely 1University Department of Medicine and Department of Haematology, The General Infirmary, Leeds LS1 3EX Search for other works by this author on: This Site PubMed Google Scholar Clin Sci (Lond) (1989) 77 (s21): 11P–12P. https://doi.org/10.1042/cs077011Pb Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share MailTo Twitter LinkedIn Cite Icon Cite Get Permissions Citation G Kumar, S Peaker, JA Davies, BE Roberts, M Feely; Increased Response to Warfarin with Age. Clin Sci (Lond) 1 December 1989; 77 (s21): 11P–12P. doi: https://doi.org/10.1042/cs077011Pb Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsClinical Science Search Advanced Search This content is only available as a PDF. © 1989 The Biochemical Society and the Medical Research Society1989 Article PDF first page preview Close Modal You do not currently have access to this content.

Fifty patients were interviewed, on discharge from hospital, about their medications. Nine (18%) patients did not know, and a further four (8%) had inappropriate beliefs about why they were taking at least one of their discharge medications. Very few patients knew of significant side-effects which they might expect, or precautions which they should take, and over half did not know how long they were to continue taking their medicines. A small proportion was unable to read the bottle or open the container. Thus, even patients who, by virtue of an in-patient stay, have had a prolonged opportunity for education regarding their medicines have very little knowledge of their medicines upon discharge from hospital.