No abstract

The utility of a new microprocessor-based method for continuous monitoring of compliance in taking solid medicaments has been evaluated. Medication intake in 31 ambulant patients was assessed in a prospective observational study under the conditions of routine practice. The patients (aged 14-87 y, mean 50 y) were receiving long-term drug treatment for various chronic diseases. There was marked interindividual and intraindividual variation in compliance with different drugs. Deviations from the prescribed dosage regimens were caused by omission of doses (22.7% of prescribed doses) and intake of extra doses (5.6% of prescribed doses). Continuous monitoring revealed that in 19% of the monitoring period no medication was taken, in 13% there was partial intake, and in 8% extra doses were taken. Patient-initiated drug holidays occurred in 50% of patients. They were responsible for 76% of the medication-free time. It is concluded, that continuous compliance monitoring is practicable in ambulatory patients. It provides information about the dynamics of drug intake behaviour that cannot be obtained from medical histories or from clinical or laboratory examination. The information could be used effectively in individual patient care and in clinical drug trials.

The objective of the study was to investigate patient compliance with two different dosage regimens. Ethinyloestradiol 80 micrograms daily was prescribed to 35 female outpatients to be taken as 20 micrograms four times daily or 40 micrograms twice daily for 7 days. It was given to standardise cervical mucus before a sperm cervical mucus penetration-test (SCMPT) was performed. Sixty-five patients with primary infertility (mean age 29.9 y) completed the study. Compliance was assessed by microprocessor-based compliance monitoring. Besides compliance (percentage of prescribed doses taken), the adherence of the patients to the dosage schedule was evaluated--'regimen compliance'. The latter parameter of drug intake behaviour was calculated by the number of days in which 2 (BID) or 4 openings (QID) were recorded by the electronic monitor. As a third parameter, the deviation from the prescribed dosing intervals, i.e. 12 or 6 h, was also determined. Partial compliance was the predominant finding and only 9 patients (13.8%) were over-compliant. Mean compliance was 75.7% in all 65 patients as a group, range 7.1 to 143%. The mean compliance with the QID regimen was 67% compared to 85% with the BID regimen. 'Regimen compliance', the percentage of doses taken on schedule, was 36% and 63% for the QID and BID regimens, respectively. Drug-intake behaviour was more erratic with the QID than the BID regimen, as indicated by the 55% of opening intervals recorded which exceeded the range of 3-9 h (mean: 6 h), compared to only 19% exceeding 6-18 h intervals (mean: 12 h).(ABSTRACT TRUNCATED AT 250 WORDS)

Using controlled long lasting noxious squeeze stimuli applied to the interdigital webs we have tried to develop experimental methods allowing us to measure the effects of peripherally acting analgesics. In the present double-blind cross-over study with 12 subjects we tested the effects of aspirin (1000 and 1500 mg) vs. placebo on subjective pain induced by alternately applied 12 N (Newton) and 8 N stimuli. During the sessions blood samples were taken in regular intervals to measure acetylsalicylate (ASA)- and salicylate (SA)-plasma levels. Analyses of variance were computed with several psychophysical parameters. Both the '12 N' and the '8 N' ratings discriminated between placebo and aspirin, however, only the ratings obtained from the stronger stimuli discriminated between two doses of aspirin. Subsequently we computed analyses of covariance with the ASA- and SA-plasma levels as covariates. Significant (negative) correlations of pain ratings and SA-plasma levels were found for the high dose of aspirin, but there were no significant correlations of ASA levels and ratings.

The objective of the study was to compare compliance with and the hypocholesterolaemic effect of lovastatin given once daily as a morning or an evening dose. Twenty-four out-patients with familial hypercholesterolaemia were randomly assigned to receive placebo first, then lovastatin 20 mg, to be taken once daily for 4 weeks, either with the breakfast or evening meal, in a single-blind fashion. Drug compliance was assessed by pill counts and continuous electronic monitoring. Two compliance parameters were evaluated, consumption, defined as percentage of prescribed doses taken, and time compliance, the percentage of total dosing events recorded within defined intervals (6.00-10.00 h, and 17.00-21.00 h), for the morning and evening regimes. Both regimes satisfactorily reduced the total and LDL-cholesterol concentrations, and there was no significant difference in the extent of the reductions. Pill counts overestimated compliance, as revealed by the monitoring method. The times of actual consumption of doses by the patients often differed from that prescribed, predominantly in patients who were told to take the evening dose. Partial time compliance may have confounded the efficacy of the drugs. Electronic compliance monitoring appears to be particularly useful in chronopharmacological studies.

Continuous electronic monitoring revealed highly variable compliance in patients prescribed maintenance therapy. Even with a once-daily regimen, persistent and high compliance cannot be assumed. The monitoring technique may be of great value to research and, possibly, to practical therapeutic management.

In four healthy subjects the intestinal absorption of levodopa (l-dopa) was investigated by measuring the plasma concentration of the amino acid following the administration of l-dopa at three different sites in the small intestine. In order to minimize presystemic clearance of l-dopa, the subjects were pretreated with the peripheral decarboxylase inhibitor benserazide 3 X 50 mg every 8 h on the previous day and 1 X 50 mg 2 h prior to administration of the l-dopa. L-dopa 100 mg dissolved in 0.05 N HCl and 50 mg benserazide dissolved in 0.05 N HCl were coadministered. Under these conditions no difference in tmax, cmax or AUC of l-dopa was observed between administration of the drug into the proximal or the distal part of duodenum, or into the upper part of jejunum. The results indicate that in healthy subjects, during inhibition of peripheral decarboxylase, the rate and extent of l-dopa absorption does not differ at any site in the upper small intestine.

Following oral administration of the uricosuric drug benzbromarone two major metabolites appear in the circulation. 1'-hydroxy-benzbromarone (M1), and a second product (M2) of unknown structure. The plasma concentrations of the parent drug and of M1 and M2 have now been compared in two different elimination phenotypes. 10 subjects who eliminated the drug rapidly (S1-10) and one individual (S11) whose elimination capacity was impaired, presumably due to genetic variation (S11). The AUC (0-96) of the parent drug in S11 was 145 micrograms.ml-1 h. and in the other individuals it averaged 18.3 (11.4-24.5) micrograms.ml-1 h. The plasma elimination half life of benzbromarone was 3.34 (1.77-5.24) h in the rapid eliminators, and 13.08 h in the subject with the elimination defect. The mean plasma elimination half life of the metabolites in S1-10 amounted to 20.1 (11.9-41.2) h for M1, and 17.2 (12.9-30.7) h for M2. In S11 the plasma elimination half life of M1 was prolonged to 76.6 h, and of M2 to 75.4 h. Thus, the elimination defect in S11 was not restricted to the parent drug, but it also involved the two major metabolites M1 and M2. This might be a consequence of a hepatic enzyme deficiency, or be due to impairment of drug excretion.