Validation of a quantitative multiplex LC-MS/MS assay of carvedilol, enalaprilat, and perindoprilat in dried blood spots from heart failure patients and its cross validation with a plasma assay.

Introduction: Adherence to medication is an important determinant of outcomes in chronic diseases like heart failure. Drug assays provide objective adherence biomarkers. Dried blood spots (DBS) are appealing samples for drug assays due to less demanding transportation and storage requirements. Objectives: To analytically validate a LC-MS/MS method for the simultaneous quantification of carvedilol, enalaprilat, and perindoprilat in DBS and evaluate the feasibility of using the method as an adherence determining assay. To validate the assay further clinically by establishing correlation and agreement between plasma and DBS samples from a pharmacokinetic pilot study. Methods: The method was validated over a concentration range of 1.00-200 ng/mL according to FDA guidelines. Adherence tracking ability of the assay was evaluated using a pharmacokinetic pilot study. Correlation and agreement were evaluated through Deming regression and Bland-Altman analysis, respectively. Results: Accuracy, precision, selectivity, and sensitivity were proven with complete and reproducible extraction recovery at all concentrations tested. Stability of the analytes in the matrix and throughout sample processing was proven. The full range of concentrations of the pharmacokinetic pilot study could be quantified for enalaprilat, but not for carvedilol and perindoprilat. The difference between the observed and calculated plasma concentrations was less than 20 % of their mean for >67 % of samples for all analytes. Conclusions: The assay is suitable as a screening tool for carvedilol and perindoprilat, while suitable as an adherence determining assay for enalaprilat. Equivalence between observed and predicted plasma concentrations proves DBS and plasma concentrations can be used interchangeably.

Objectively measured medication adherence using assays for carvedilol and enalaprilat in patients with heart failure in Mozambique and Nigeria.

Background: Poor medication adherence leads to poor health outcomes and increased healthcare costs among patients with heart failure (HF). This study aimed to objectively assess medication adherence by measuring carvedilol and enalaprilat plasma concentrations among patients with HF. Methods: The present sub-study of the Safety, Tolerability, and Efficacy of Rapid Optimization, helped by NT-proBNP testing, of Heart Failure therapies (STRONG-HF) study involved adult patients with acute HF admitted in two Mozambican and two Nigerian hospitals who were not optimally treated with oral enalapril and carvedilol. Patients in the high-intensity arm of the STRONG-HF study, and those not meeting the biomarker criteria for persistent congestion, were included in the "frequent visit" (FV) arm. In the FV arm, blood for bioanalysis of plasma enalaprilat or/and carvedilol was drawn at the 2,6,12th week post-discharge. Patients in the usual care arm of STRONG-HF were included in the "standard visit" (SV) arm, which followed the usual local practice with blood sampling in week 12. Results: The study involved 113 (79 FV and 34 SV) participants with a mean age of 48.6 years and a mean left ventricular (LV) ejection fraction of 33.1%. Theenalaprilat below the lower level of quantification (LLOQ) was documented in 7.7%, 11.9%, and 15.6% of participants in FV during the 2,6 and 12th weeks. Carvedilol concentration below LLOQ was documented in 37%, 30%, and 44.4% of participants in the FV arm during the 2,6 and 12th weeks, respectively. For the SV arm, enalaprilat and carvedilol concentrations below LLOQ in the twelfth week were documented in 37.3% and 42.9% of patients, respectively. Conclusion: Up to a third of patients using enalapril and carvedilol did not take any medication during the 12 weeks of follow-up. Non adherence was more common in patients who had less follow up, emphasizing the importance of close follow up to adherence. No adherence was also more common in medications know to have more side effects such as carvedilol.

Treatment of schizophrenia in low-income countries.

The introduction of the novel antipsychotics has had a major impact upon the treatment of schizophrenia. However, the greater acquisition costs of these drugs puts them beyond the reach of large sectors of the world's population. Consequently, the gap between the levels of care in high-income and low-income countries is likely to widen even further. Co-ordinated global action is necessary to ensure greater accessibility of these drugs. Cost-effectiveness studies in low-income countries need to be undertaken. The considerable evidence for improved safety and efficacy of low-dose compared to high-dose classical antipsychotics offers an alternative that could be implemented immediately in low-income countries.

Providing quality care to patients with schizophrenia.

With the increasing use of evidence-based medicine and the welcome introduction of innovations such as computer technology into daily practice, there is now the opportunity to link these two new approaches to the awareness of quality measurement within psychiatry. As awareness of costs in medical treatment increases, the emphasis on quality management increases, which makes it increasingly more important that quality standards are set using the available treatment guidelines. When set, these standards can be applied and eventually measured. Only then can quality management be put into practice. The use of treatment guidelines for the holistic treatment of psychiatry patients now is being actively encouraged in many treatment settings. These guidelines form a potential basis for more effective treatment. Only by implementing a measurement process of treatment outcomes will the true value of these guidelines be appreciated.

Citalopram.

Citalopram is a selective serotonin (5-HT) reuptake inhibitor (SSRI) developed by H. Lundbeck A/S in Denmark. It is the most selective serotonin antidepressant with proven efficacy, a favourable pharmacokinetic profile and a low potential for interactions with other concomitant medication. The drug has a low incidence of side effects, even when compared to the other SSRIs and good patient compliance and satisfaction is a feature of this drug. These factors make the drug a good choice for depressed patients who require continuation and long-term treatment, as well as for elderly patients. Copyright 2000 John Wiley & Sons, Ltd.