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PubMed2006

Therapeutic drug monitoring of antidepressants and cytochrome p450 genotyping in general practice.

In the psychiatric setting, therapeutic drug monitoring and genotyping for cytochrome P450 (CYP) polymorphisms help to ensure and maintain therapeutic drug levels. In this study, the authors extended the therapeutic drug monitoring and genotyping protocol routinely used in their psychiatric clinic to primary care patients treated with antidepressants. They examined the variation in serum concentrations and assessed the role of CYP polymorphisms, wrong dosing, and noncompliance in deviating serum concentrations. Of 227 serum concentrations obtained, 127 (56%) were more than 20% outside therapeutic ranges. Of these 127 cases, 64 (50%) were congruous with aberrant CYP2D6 or CYP2C19 genotypes, incorrect dosing, or a pharmacy record suggesting noncompliance. Prevalence of aberrant CYP2D6 and CYP2C19 genotypes did not differ significantly between the investigated primary care patients and 751 secondary care users of antidepressants. The therapeutic drug monitoring and the genotyping findings resulted in recommendations to physicians to alter the medication strategy of 146 (64%) patients. These results strongly suggest that the rationale for therapeutic drug monitoring and CYP genotyping when prescribing antidepressants in secondary care also applies to the primary care setting.

Antidepressive Agents↗
PubMed1993

Therapeutic touch and postoperative pain: a Rogerian research study.

This article details Meehan's research study concerning the conceptualization of therapeutic touch within Rogers' science of unitary human beings and an investigation of the effects of therapeutic touch on pain experience in postoperative patients. Using a single trial, single-blind, three-group design, 108 postoperative patients were randomly assigned to receive one of the following: therapeutic touch, a placebo control intervention which mimicked therapeutic touch, or the standard intervention of a narcotic analgesic. Using a visual analogue scale, pain was measured before and one hour following intervention. The hypothesis, that therapeutic touch would significantly decrease postoperative pain compared to the placebo control intervention, was not supported. Secondary analyses suggest that therapeutic touch may decrease patients' need for analgesic medication. Implications for further research and practice are suggested.

Adult↗
PubMed1989

Probability assessment approach to therapeutic drug monitoring: tobramycin.

Pharmacokinetic monitoring is an important therapeutic goal of aminoglycoside therapy. The overall goal of this study was to identify specific patient groups that would derive the maximum benefit from therapeutic drug monitoring services. These groups are patient populations with high probabilities of achieving toxic or subtherapeutic concentrations. Out of a total population of 86 stable, noncritically ill patients, 27 toxic concentrations (trough greater than 2.0 micrograms/mL) occurred in 15 patients. In comparison to patients (n = 46) with therapeutic concentrations (trough less than 2.0 micrograms/mL, peak greater than 4.0 micrograms/mL), these patients were older (64 +/- 11 vs. 54 +/- 18 years; p less than 0.02) and had a higher percentage of females (66.7 vs. 37 percent; p less than 0.05). Those patients with subtherapeutic concentrations (43 concentrations in 25 patients) had higher estimated creatinine clearance values than those with therapeutic concentrations (94 +/- 45 vs. 74 +/- 27 mL/min; p less than 0.005). Probability assessment analysis of the data showed a sevenfold increase in toxic concentrations in patients above 50 years. Females over age 50 had 2.3 times the risk of developing toxic concentrations as males over age 50. In contrast, the development of low concentrations was not predicted by age or sex. Underdosage by greater than or equal to 30 percent was a reasonable predictor (75 percent) of low peak concentrations. Furthermore, toxic concentrations did not occur in patients who were underdosed, justifying dosage increases prior to obtaining serum concentrations in these patients. The group with the highest probability of attaining therapeutic concentrations was males receiving therapeutic doses who were under age 50 (85.5 percent).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2002

Endobronchial ultrasound in therapeutic bronchoscopy.

Endobronchial ultrasound (EBUS) has been introduced as an adjunct to diagnostic bronchoscopy as it allows evaluation of the submucosal and parabronchial structures. Its use in therapeutic bronchoscopy has not been assessed. A large observational study of the value of EBUS in therapeutic bronchoscopy is presented here. From January 1998-January 2001 all patients undergoing therapeutic bronchoscopy and EBUS were evaluated prospectively. Patient demographics, indication for bronchoscopy, interventional treatments used and changes in therapy as influenced by the use of EBUS were documented. A total 2,446 therapeutic bronchoscopies were performed. In 1,174 cases EBUS was used (29% mechanical tumour debridement, 20% airway stenting, 13% Neodymium:yttrium aluminium garnet (Nd:YAG) laser use, 23% argon plasma coagulation, 11% brachytherapy, 2% foreign body removal and 2% endoscopic abscess drainage). EBUS guided or changed therapy significantly in 43% of cases. Changes included adjustment of stent dimensions, termination of tumour debridement when nearing vessels, and referral for surgical interventions rather than endoscopic treatment. Complications associated with EBUS use were minimal. No patient undergoing EBUS guided tumour destruction experienced severe bleeding or fistula formation. In summary, endobronchial ultrasound was easily performed and changed or guided therapeutic decisions during therapeutic bronchoscopic procedures in a substantial number of cases. As this may result in better outcomes, it has become a standard adjunct in the authors practice.

Adult↗
PubMed2004

Audit of therapeutic interventions in inpatient children using two scores: are they evidence-based in developing countries?

BACKGROUND: The evidence base of clinical interventions in paediatric hospitals of developing countries has not been formally assessed. We performed this study to determine the proportion of evidence-based therapeutic interventions in a paediatric referral hospital of a developing country METHODS: The medical records of 167 patients admitted in one-month period were revised. Primary diagnosis and primary therapeutic interventions were determined for each patient. A systematic search was performed to assess the level of evidence for each intervention. Therapeutic interventions were classified using the Ellis score and the Oxford Centre for Evidence Based Medicine Levels of Evidence RESULTS: Any dehydration due to diarrhoea (59 cases) and pneumonia (42 cases) were the most frequent diagnoses. Based on Ellis score, level I evidence supported the primary therapeutic intervention in 21%, level II in 73% and level III in 6% cases. Using the Oxford classification 16%, 8%, 1% and 75% therapeutic interventions corresponded to grades A, B, C, and D recommendations, respectively. Overall, according to Ellis score, 94% interventions were evidence based. However, out of the total, 75% interventions were based on expert opinion or basic sciences. Most children with mild to moderate dehydration (52 cases) were inappropriately treated with slow intravenous fluids, and most children with non-complicated community acquired pneumonia (42 cases) received intravenous antibiotics CONCLUSIONS: Most interventions were inappropriate, despite the availability of effective therapy for several of them. Diarrhoeal dehydration and community acquired pneumonia were the most common diagnoses and were inappropriately managed. Existing effective interventions for dehydration and pneumonia need to be put into practice at referral hospitals of developing countries. For the remaining problems, there is the need to conduct appropriate clinical studies. Caution must be taken when assigning the level of evidence supporting therapeutic interventions, as commonly used classifications may be misleading.

Child↗
PubMed2003

Challenges of developing therapeutics that target signal transduction in patients with gynecologic and other malignancies.

A greater understanding of cancer biology and major advances in biotechnology have resulted in the identification of a plethora of rationally designed, target-based anticancer therapeutics, particularly those that inhibit malignant-cell signal transduction, ushering in new therapeutic opportunities and extraordinary developmental challenges. Because these agents seem to principally target malignant cells, it is expected that they will produce less toxicity at clinically effective doses than nonspecific cytotoxic agents. The innate complexity of signaling networks, which have redundant relay systems that confer robustness, adaptability, and signaling diversity, also decreases the probability that any single therapeutic manipulation against any specific signaling element will be highly successful when used alone, particularly in patients with solid malignancies that have multiple relevant signaling aberrations. In addition, because the predominant therapeutic effect of inhibitors of signal transduction processes in preclinical studies is a decreased rate of tumor growth, it is anticipated that the predominant therapeutic outcome in the clinic will be similar; however, this end point is not readily detectable or quantifiable using traditional clinical evaluation methods. Furthermore, the results of preclinical and early clinical studies indicate that dose-toxicity relationships are not likely to be as steep as with nonspecific cytotoxic agents. Therefore, both regulatory and clinical practice end points, such as time to disease progression, disease-related symptoms, and quality of life, which are generally considered secondary for cytotoxic agents, may evolve into primary end points. The cumulative results of developmental evaluations to date indicate that the development, evaluation, and general clinical use of rationally designed, target-based anticancer therapeutics will require a radical departure from traditional paradigms to exploit the full potential of these new therapies.

Animals↗
PubMed2003

Therapeutic hypercapnia is not protective in the in vivo surfactant-depleted rabbit lung.

Permissive hypercapnia because of reduced tidal volume is associated with improved survival in lung injury, whereas therapeutic hypercapnia-deliberate elevation of arterial Pco2-protects against in vivo reperfusion injury and injury produced by severe lung stretch. No published studies to date have examined the effects of CO2 on in vivo models of neonatal lung injury. We used an established in vivo rabbit model of surfactant depletion to investigate whether therapeutic hypercapnia would improve oxygenation and protect against ventilator-induced lung injury. Animals were randomized to injurious (tidal volume, 12 mL/kg; positive end-expiratory pressure, 0 cm H2O) or protective ventilatory strategy (tidal volume, 5 mL/kg; positive end-expiratory pressure, 12.5 cm H2O), and to receive either control conditions or therapeutic hypercapnia (fraction of inspired CO2, 0.12). Oxygenation (alveolar-arterial O2 difference, arterial Po2), lung injury (alveolar-capillary protein leak, impairment of static compliance), and selected bronchoalveolar lavage and plasma cytokines (IL-8, growth-related oncogene, monocyte chemoattractant protein-1, and tumor necrosis factor-alpha) were measured. Injurious ventilation resulted in a large alveolar-arterial O2 gradient, elevated peak airway pressure, increased protein leak, and impaired lung compliance. Therapeutic hypercapnia did not affect any of these outcomes. Tumor necrosis factor-alpha was not increased by mechanical stretch in any of the groups. Therapeutic hypercapnia abolished the stretch-induced increase in bronchoalveolar lavage monocyte chemoattractant protein-1, but did not affect any of the other mediators studied. Therapeutic hypercapnia may attenuate the impairment in oxygenation and inhibit certain cytokines. Because hypercapnia inhibits certain cytokines but does not alter lung injury, the pathogenic role of these cytokines in lung injury is questionable.

Acid-Base Equilibrium↗
PubMed1999

Barriers to treatment participation and therapeutic change among children referred for conduct disorder.

Examined predictors of therapeutic change among children seen in outpatient therapy. Children (N = 200) referred for oppositional, aggressive, and antisocial behavior and their families participated. The major findings were that (a) socioeconomic disadvantage, parent psychopathology and stress, and child dysfunction predicted therapeutic change from pretreatment to posttreatment; (b) barriers to participation in treatment also were significantly associated with therapeutic change and this effect was not explained by the other family, parent, and child predictors; (c) as the level of perceived barriers to participation in treatment increased among families, the amount of therapeutic change decreased; and (d) among children at risk for relatively little therapeutic change, the perception of few barriers to treatment increased the degree of child improvement. The implications for further work on predictors of therapeutic change and the role of barriers in the treatment process are discussed.

Adolescent↗
PubMed2005

A case of stunning of lung and bone metastases of papillary thyroid cancer after a therapeutic dose (3.7 GBq) of 131I and review of the literature: implications for sequential treatments.

Thyroid stunning is usually defined as the inhibition or suppression of iodide trapping by remnant thyroid tissue or by functioning metastases following a diagnostic dose of 131I. The risk of stunning increases progressively with larger doses. Because the threshold above which this effect occurs in thyroid remnants seems to be between 37 MBq and 111 MBq of 131I, therapeutic 131I doses of 3.7 GBq may cause stunning. We describe stunning of papillary thyroid cancer lung and bone metastases after a therapeutic dose of 131I (3.7 GBq). A T1 bone metastasis and bilateral lung metastases were diagnosed by post-therapeutic dose whole-body scan. Nuclear MRI detected another lesion at T4, whose 131I fixation was not obvious. An additional 0.7 GBq were given after recombinant TSH, 37 days after the therapeutic dose; 24 h later, uptake by the lung and T1 metastases had disappeared, but trapping was again seen 6 months later on the post-therapeutic scan. This re-appearance is evidence in favour of the transitory and reversible character of stunning, and confirms its correspondence to the decreased ability of viable thyroid cells to trap iodine and not to their destruction. A better understanding of stunning would make it possible, in the event of rapidly progressing disease and in conjunction with recombinant thyroid stimulating hormone (TSH), to give several therapeutic doses of 131I in close succession without each dose hampering the effectiveness of the subsequent one.

Adolescent↗
PubMedDate not supplied

A critical evaluation of the therapeutic range of indinavir.

OBJECTIVE: To provide a summary of the patient population, study characteristics, and important findings of the key studies in the literature evaluating concentration-effect relationships and the therapeutic range for indinavir. DATA SOURCES: Literature search strategy involved using MEDLINE (1966-July 2001) and AIDSLINE (MEDSCAPE) databases (up to July 2001). Reference lists from primary literature and review articles were also examined, and conference abstracts were obtained. STUDY SELECTION: English-language articles were considered suitable for review if the clinical trials in HIV patients reported on concentration-effect relationships and/or pharmacokinetic breakpoints or threshold concentrations. A search of the literature identified 20 peer-reviewed references from 18 separate studies including journal articles and conference abstracts. DATA EXTRACTION: The targeted pharmacokinetic parameters and breakpoint values, the rationale for their selection or method of identification, and other study details and limitations were summarized. DISCUSSION: This article highlights the heterogeneity of studies evaluating the therapeutic range of indinavir and provides a summary of important findings of the key studies in the literature evaluating concentration-effect relationships and therapeutic range. Tables are provided to enable clinicians to make use of currently available information on the therapeutic range of indinavir. CONCLUSIONS: There is insufficient evidence to recommend a general therapeutic range for indinavir. Future investigations should incorporate both pharmacokinetics and pharmacodynamics in order to define a broadly applicable therapeutic range.

Adult↗
PubMed1999

The utility of daily therapeutic thoracentesis for the treatment of early empyema.

STUDY OBJECTIVES: To determine if therapeutic thoracentesis is as effective as early chest tube placement or no drainage procedure in the treatment of early empyema in rabbits. DESIGN AND INTERVENTIONS: An empyema, as evidenced by gross pleural pus and a decreased pleural fluid pH and glucose level, was induced in 49 rabbits. The rabbits were divided into three groups: 16 underwent daily therapeutic thoracentesis starting at 48 h, 14 underwent chest tube placement at 48 h, and 19 served as controls. RESULTS: The mortality rate in the therapeutic thoracentesis group (0/16) did not differ significantly from that in the chest tube group (3/14) or that in the control group (6/19). At autopsy at 10 days, the gross empyema score in the therapeutic thoracentesis group (2.1 +/- 0.3) was significantly lower (p < 0.05) than that in the chest tube group (2. 8 +/- 0.3) or the control group (3.5 +/- 0.2). The mean pleural peel score of 5.8 +/- 1.1 in the therapeutic thoracentesis group was significantly less (p < 0.05) than the score for the nonintervention control group (13.4 +/- 1.6). CONCLUSIONS: From this study, we conclude that therapeutic thoracentesis is at least as effective as early chest tube placement for the treatment of early empyema using our rabbit model of empyema.

Animals↗
PubMed2003

Evaluation of unattended automated titration to determine therapeutic continuous positive airway pressure in patients with obstructive sleep apnea.

BACKGROUND: Determination of the therapeutic pressure during continuous positive airway pressure (CPAP) therapy is usually performed by a technician during polysomnography. In recent years, several devices for automated adjustment of the therapeutic pressure by the means of computerized algorithms were developed. The aims of the present study were to compare two different devices for automated titration and to verify if unattended automated titration is a feasible strategy to determine the therapeutic CPAP. METHODS: We enrolled 16 consecutive patients with obstructive sleep apnea syndrome (OSAS) defined by an apnea-hypopnea index > 20/h. Automated titration was performed in the hospital using two CPAP devices (Autoset; Resmed; North Ryde, Australia; and Somnosmart; Weinmann; Hamburg, Germany) in random order for 2 consecutive nights, based on different signals for the detection of respiratory events. During titration, there was no direct supervision by a technician, and polysomnography was not recorded. We defined the therapeutic pressure as the 95th percentile of the airway pressure over time (P95). RESULTS: We observed significant differences of the P95 between the two devices, with an average of 7.0 +/- 2.5 cm H(2)O for the Somnosmart and 9.9 +/- 2.6 cm H(2)O for the Autoset (p = 0.005) [mean +/- SD]. There was a considerable lack of agreement between the two devices, with a bias of 3.0 cm H(2)O and limits of agreement ranging from + 9.3 to - 3.2 cm H(2)O. We found no significant correlation between the paired differences of P95 and either indexes of severity of OSAS or lung function variables. CONCLUSION: Automated titration based on the analyses of flow (Autoset) or forced oscillations (Somnosmart) predicted significant different therapeutic pressures for fixed CPAP therapy. Thus, unattended automated titration performed during 1 night of hospital stay with commercially available devices cannot be used to determine accurately the therapeutic CPAP in patients with OSAS.

Automation↗
PubMed2004

Therapeutic angiogenesis for myocardial ischemia.

Therapeutic angiogenesis offers promise as a novel treatment for ischemic heart disease, particularly for patients who are not candidates for current methods of revascularization. The goal of treatment is both relief of symptoms of coronary artery disease and improvement of cardiac function by increasing perfusion to the ischemic region. Protein-based therapy with cytokines including vascular endothelial growth factor and fibroblast growth factor demonstrated functionally significant angiogenesis in several animal models. However, clinical trials have yielded largely disappointing results. The attenuated angiogenic response seen in clinical trials of patients with coronary artery disease may be due to multiple factors including endothelial dysfunction, particularly in the context of advanced atherosclerotic disease and associated comorbid conditions, regimens of single agents, as well as inefficiencies of current delivery methods. Gene therapy has several advantages over protein therapy and recent advances in gene transfer techniques have improved the feasibility of this approach. The safety and tolerability of therapeutic angiogenesis by gene transfer has been demonstrated in phase I clinical trials. The utility of therapeutic angiogenesis by gene transfer as a treatment option for ischemic cardiovascular disease will be determined by adequately powered, randomized, placebo-controlled Phase II and III clinical trials. Cell-based therapies offer yet another approach to therapeutic angiogenesis. Although it is a promising therapeutic strategy, additional preclinical studies are warranted to determine the optimal cell type to be administered, as well as the optimal delivery method. It is likely the optimal treatment will involve multiple agents as angiogenesis is a complex process involving a large cascade of cytokines, as well as cells and extracellular matrix, and administration of a single factor may be insufficient. The promise of therapeutic angiogenesis as a novel treatment for no-option patients should be approached with cautious optimism as the field progresses.

Angiogenesis Inducing Agents↗
PubMed2004

Therapeutic effects of hyaluronic acid on osteoarthritis of the knee. A meta-analysis of randomized controlled trials.

BACKGROUND: The magnitude of the therapeutic effects of intra-articular injection of hyaluronic acid on osteoarthritis of the knee is still in question. The aim of this meta-analysis was to elucidate the therapeutic efficacy and safety of intra-articular injection of hyaluronic acid for osteoarthritis of the knee. METHODS: We conducted a meta-analysis of twenty blinded randomized controlled trials that compared the therapeutic effect of intra-articular injection of hyaluronic acid with that of intra-articular injection of a placebo to treat osteoarthritis of the knee. The outcome end points were classified into three categories: pain with activities, pain without activities, and function. The outcome measures of the efficacy of hyaluronic acid were the mean differences in the efficacy scores between the hyaluronic acid and placebo groups. The outcome measure of the safety of hyaluronic acid was the relative risk of adverse events. RESULTS: Intra-articular injection of hyaluronic acid can decrease symptoms of osteoarthritis of the knee. We found significant improvements in pain and functional outcomes with few adverse events. However, there was significant between-study heterogeneity in the estimates of the efficacy of hyaluronic acid. Subgroup analysis and meta-regression analysis showed that lower methodological quality such as a single-blind or single-center design resulted in higher estimates of hyaluronic acid efficacy, that introduction of acetaminophen as an escape analgesic in the trial resulted in lower estimates of hyaluronic acid efficacy, and that patients older than sixty-five years of age and those with the most advanced radiographic stage of osteoarthritis (complete loss of the joint space) were less likely to benefit from intra-articular injection of hyaluronic acid. CONCLUSIONS: This meta-analysis confirmed the therapeutic efficacy and safety of intra-articular injection of hyaluronic acid for the treatment of osteoarthritis of the knee. Additional well-designed randomized controlled trials with high methodological quality are needed to resolve the continued uncertainty about the therapeutic effects of different types of hyaluronic acid products on osteoarthritis of the knee in various clinical situations and patient populations. LEVEL OF EVIDENCE: Therapeutic study, Level II-3b (systematic review; nonhomogeneous Level-I studies). See Instructions to Authors for a complete description of levels of evidence.

Activities of Daily Living↗
PubMed2003

Clinical development of therapeutic recombinant proteins.

Only a small subset of the therapeutics that enter clinical studies will prove to be safe and effective in humans and gain approval for marketing. The success of the products and, by inference, the sponsoring companies can be measured by tracking advancement through the clinical phase and review transitions to marketing approval. To determine phase transition probabilities and approval success rates for recombinant protein (rDNA) therapeutics, the Tufts Center for the Study of Drug Development collected data for 271 rDNA therapeutics that entered clinical study between 1980 and 2002. The data were stratified into eight therapeutic categories. Approval success rates were calculated for rDNA therapeutics with two possible fates: (i) approval in any country and (ii) U.S. approval only. Global approval success rates ranged from 23% to 63%, and U.S. approval success rates ranged from 17% to 58%. Trends in clinical phase lengths over five time periods and an overview of the rDNA therapeutics currently under Food and Drug Administration review are discussed.

Clinical Trials as Topic↗
PubMed1987

Therapeutic drug monitoring in oncology. Problems and potential in antineoplastic therapy.

Therapeutic drug monitoring is now widely used in many areas of medicine. With its proliferation has come an understanding of the clinical situations in which it is likely to be of value. Factors that can limit the usefulness of therapeutic drug monitoring and situations where it is less likely to be of benefit have also been identified. At present, the routine use of therapeutic drug monitoring in antineoplastic therapy is limited to measurement of plasma methotrexate concentrations after high-dose methotrexate therapy. The lack of a more widespread application of therapeutic drug monitoring in oncology has been due to deficiencies in knowledge about the clinical pharmacology of antineoplastic agents and to factors specific to the chemotherapy of neoplasms. These factors include the broad heterogeneity of malignant neoplasms, the complexities of the drug-tumour interaction, difficulties in assessment of this interaction and the use of combinations of antineoplastic agents with cumulative efficacies and toxicities. Despite these problems, there are many areas in antineoplastic therapy where the use of therapeutic drug monitoring could prove of benefit. The prevention of the chronic pulmonary toxicity of bleomycin, the assessment of the bioavailability of oral chemotherapy, and monitoring drug disposition in the presence of hepatic or renal dysfunction are just some of the potential applications. If recent emphasis on dose as a critical factor in the success of cancer chemotherapy is substantiated, then the need to apply therapeutic drug monitoring within oncology will become more pressing.

Antineoplastic Agents↗
PubMed1999

Therapeutic drug concentration monitoring using saliva samples. Focus on anticonvulsants.

In the last 30 years there has been great interest in the use of saliva in therapeutic drug monitoring. Numerous investigators have suggested that saliva be used as an alternative body fluid for the therapeutic drug monitoring of anticonvulsant drugs. Not only can saliva be obtained easily on multiple occasions with minimal discomfort to the patient but, more importantly, useful relationships exist between the saliva and blood concentrations of the most commonly used anticonvulsant drugs. The measurement of anticonvulsant drug concentrations in saliva has been applied to pharmacokinetic and pharmacodynamic studies, and for therapeutic drug monitoring in a variety of seizure disorders. However, this simple and non-invasive method is not widely accepted in clinical practice. Several recent developments in sample collection and analytical methods, and the growing interest in free drug concentrations, provide a renewed impetus for saliva sampling for therapeutic drug monitoring of anticonvulsant drugs. Salivary flow rates vary significantly both between individuals and under different conditions. The use of stimulated saliva has several advantages over resting saliva. The salivary flow rate and pH, sampling conditions, contamination and many other pathophysiological factors may influence the concentrations of the medication in saliva. However, under standardised and well-controlled sampling condition, therapeutic drug monitoring of anticonvulsant drugs in saliva can be useful for determining compliance with medication in paediatric patients, for analysing the concentration of free drug and in situations where repeated sampling is necessary. Saliva is an alternative matrix for the therapeutic drug monitoring of carbamazepine, phenytoin, primidone and ethosuximide because the concentrations of these medications in saliva reflect the concentrations of the drug in serum. This is not the case for valproic acid (valproate sodium) and some controversy exists for phenobarbital. Further studies are required to assess the clinical value of monitoring anticonvulsant drugs and their metabolites in saliva, to examine the influence of pathophysiological factors on salivary drug concentrations, to improve the design of special devices to reproducibly and conveniently collect saliva samples, and to develop and use new analytical methods to achieve more sensitive and accurate results.

Anticonvulsants↗
PubMed2003

Therapeutic drug monitoring of antiarrhythmic drugs.

Most antiarrhythmic drugs fulfil the formal requirements for rational use of therapeutic drug monitoring, as they show highly variable plasma concentration profiles at a given dose and a direct concentration-effect relationship. Therapeutic ranges for antiarrhythmic drugs are, however, often very poorly defined. Effective drug concentrations are based on small studies or studies not designed to establish a therapeutic range, with varying dosage regimens and unstandardised sampling procedures. There are large numbers of nonresponders and considerable overlap between therapeutic and toxic concentrations. Furthermore, no study has ever shown that therapeutic drug monitoring makes a significant difference in clinical outcome. Therapeutic concentration ranges for antiarrhythmic drugs as they exist today can give an overall impression about the drug concentrations required in the majority of patients. They may also be helpful for dosage adjustment in patients with renal or hepatic failure or in patients with possible toxicological or compliance problems. Their use in optimising individual antiarrhythmic therapy, however, is very limited.

Anti-Arrhythmia Agents↗