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Biomedical subjects

J E Tisdale

Publications and source records attributed to J E Tisdale.

At least 19 recordsLinked to original sources
PubMed2001

The effect of intravenous haloperidol on QT interval dispersion in critically ill patients: comparison with QT interval prolongation for assessment of risk of Torsades de Pointes.

The objective of this study was to determine the effect of intravenous haloperidol on QT interval dispersion in critically ill patients and to compare increases in QT interval dispersion and QTc intervals in patients who developed haloperidol-induced Torsades de Pointes versus those in patients who did not. This was a case-controlled study of 30 critically ill patients who received intravenous haloperidol for delusional agitation. Cases were patients (n = 6) who developed Torsades de Pointes during haloperidol therapy. Controls were patients (n = 24) who did not experience haloperidol-induced Torsades dePointes. QTc intervals were measured and QT interval dispersion was calculated. Haloperidol prolonged QTc interval compared to pretreatment values in Torsades de Pointes patients (606 +/- 61 ms vs. 501 +/- 44 ms, p = 0.007) by a greater magnitude than in patients who did not experience Torsades de Pointes (507 +/- 60 ms vs. 466 +/- 44, p = 0.01). Twelve-lead analysis revealed that QT interval dispersion increased in patients who experienced Torsades de Pointes (from 63 +/- 11 to 95 +/- 22 ms, p = 0.03) but not in those who did not (62 +/- 18 vs. 60 +/- 26 ms, p = 0.66). Analysis of precordial leads only showed no significant haloperidol-associated increases in QTinterval dispersion in eithergroup. The odds of developing haloperidol-induced Torsades de Pointes were highest in patients with QTc interval > 521 ms during haloperidol therapy(odds ratio = 12.1). It was concluded that intravenous haloperidol prolongs QTc intervals in critically ill patients. The degree of prolongation is greater in patients who experience Torsades de Pointes. QT interval dispersion may be increased in patients who develop haloperidol-induced Torsades de Pointes compared with those who do not. However, these effects are dependent on the method of measurement (12 leads vs. precordial leads). In addition, the odds of haloperidol-induced Torsades de Pointes are higherin patients with QTc intervalprolongation compared with increased QT interval dispersion. Therefore, QTc interval determination remains preferable to QT interval dispersion as a means assessment of risk for haloperidol-induced Torsades de Pointes.

Aged↗
PubMed2000

The use of calcium salts in the prevention and management of verapamil-induced hypotension.

OBJECTIVE: To review the available literature on the use of intravenous calcium salts for the prevention of hypotension associated with intravenous verapamil. METHODS: A MEDLINE search (1966-June 1999) identified pertinent articles; references from these articles were identified to serve as additional resources. DISCUSSION: Verapamil is effective in inhibiting atrioventricular nodal conduction, thereby controlling ventricular rate in patients with atrial fibrillation/flutter and terminating paroxysmal supraventricular tachycardia. However, hypotension may be caused by the negative inotropic and vasodilating effects of verapamil. In vitro and animal data suggest that calcium pretreatment may minimize the effects of verapamil on cardiac output and blood pressure. Case reports suggest that intravenous calcium may be useful for both prevention and reversal of the hemodynamic effects of verapamil. A number of small clinical trials have been performed, suggesting that calcium administered prior to intravenous verapamil results in a decreased incidence of hypotension. The most common adverse effect of intravenous calcium is flushing. CONCLUSIONS: Calcium pretreatment prior to intravenous calcium-channel blocker administration should be considered in patients in whom further reductions in blood pressure may precipitate hypoperfusion or worsen underlying cardiovascular status. A dose of calcium gluconate 1 g (ionized calcium 90 mg) administered over three minutes is recommended for preventing or lessening the hypotensive effect of verapamil without affecting the antiarrhythmic effects of verapamil.

Calcium Channel Blockers↗
PubMed1999

Low-molecular-weight heparins in the management of acute coronary syndromes.

Acute coronary syndromes (unstable angina and non-Q-wave myocardial infarction) are caused by the rupture of an atherosclerotic plaque, platelet activation, and fibrin deposition resulting in thrombosis. Aspirin and unfractionated heparin have traditionally been the treatments of choice for patients with acute coronary syndromes. Low-molecular-weight heparins offer potential advantages over unfractionated heparin, having proven equally effective for the treatment and prevention of many thromboembolic processes. Recently, a number of randomized controlled trials have been conducted to evaluate the role of low-molecular-weight heparins in the management of patients with unstable angina or non-Q-wave myocardial infarction. The purpose of this article is to review and evaluate the available literature on the use of low-molecular-weight heparins in the management of acute coronary syndromes to establish their role in therapy.

Angina, Unstable↗
PubMed1998

Antiplatelet therapy in coronary artery disease: review and update of efficacy studies.

The mechanisms of action of currently available and newer antiplatelet agents and evidence of the efficacy of antiplatelet agents for primary and secondary prevention of coronary artery disease are reviewed. Available data do not support the widespread use of aspirin for primary prevention of cardiovascular disease. Patients over the age of 50 years with at least one additional risk factor for coronary artery disease may benefit, although possibly at an increased risk of hemorrhagic stroke. Aspirin is recommended for secondary prevention of vascular disease in patients with stable or unstable angina, clinical or laboratory evidence of coronary artery disease, history of myocardial infarction, or history of stroke or transient ischemic attack. There are no data supporting a role for dipyridamole for primary or secondary prevention of ischemic heart disease. Abciximab has been shown to reduce the risk of cardiovascular complications at 30 days after percutaneous transluminal coronary angioplasty in patients with refractory unstable angina. Studies with other glycoprotein IIb/IIIa-receptor antagonists, including eptifibatide, tirofiban, and lamifiban, have yielded promising results. Ticlopidine may be used for secondary prevention of cardiovascular disease in patients with unstable angina who are allergic to or intolerant of aspirin. Clopidogrel has been shown to be safe and effective for secondary prevention of vascular events. Aspirin has a role in secondary prevention of coronary artery disease; among patients who are allergic to or intolerant of aspirin, ticlopidine has a role in patients with unstable angina and clopidogrel has a potential role in patients with ischemic heart or vascular disease.

Abciximab↗
PubMed1998

Torsades de Pointes associated with intravenous haloperidol in critically ill patients.

In this retrospective case-control study, 8 of 223 consecutive patients (3.6%) treated with intravenous haloperidol developed torsades de pointes, and were compared with 41 patients randomly selected as controls. The likelihood of torsades de pointes associated with intravenous haloperidol is significantly greater in patients receiving > or = 35 mg over 24 hours or in those with a QTc interval of >500 ms, or both.

Adult↗
PubMed1998

A randomized, double-blind comparison of intravenous diltiazem and digoxin for atrial fibrillation after coronary artery bypass surgery.

BACKGROUND: Atrial fibrillation (AF) after coronary bypass graft surgery may result in hypotension, heart failure symptoms, embolic complications, and prolongation in length of hospital stay (LOHS). The purpose of this study was to determine whether intravenous diltiazem is more effective than digoxin for ventricular rate control in AF after coronary artery bypass graft surgery. A secondary end point was to determine whether ventricular rate control with diltiazem reduces postoperative LOHS compared with digoxin. METHODS AND RESULTS: Patients with AF and ventricular rate > 100 beats/min within 7 days after coronary artery bypass graft surgery were randomly assigned to receive intravenous therapy with diltiazem (n = 20) or digoxin (n = 20). Efficacy was measured with ambulatory electrocardiography (Holter monitoring). Safety was assessed by clinical monitoring and electrocardiographic recording. LOHS was measured from the day of surgery. Data were analyzed with the intention-to-treat principle in all randomly assigned patients. In addition, a separate intention-to-treat analysis was performed excluding patients who spontaneously converted to sinus rhythm. In the analysis of all randomly assigned patients, those who received diltiazem achieved ventricular rate control (> or = 20% decrease in pretreatment ventricular rate) in a mean of 10 +/- 20 (median 2) minutes compared with 352 +/- 312 (median 228) minutes for patients who received digoxin (p < 0.0001). At 2 hours, the proportion of patients who achieved rate control was significantly higher in patients treated with diltiazem (75% vs 35%, p = 0.03). Similarly, at 6 hours, the response rate associated with diltiazem was higher than that in the digoxin group (85% vs 45%, p = 0.02). However, response rates associated with diltiazem and digoxin at 12 and 24 hours were not significantly different. At 24 hours, conversion to sinus rhythm had occurred in 11 of 20 (55%) patients receiving diltiazem and 13 of 20 (65%) patients receiving digoxin (p = 0.75). Results of the analysis of only those patients who remained in AF were similar to those presented above. There was no difference between the diltiazem-treated and digoxin-treated groups in postoperative LOHS (8.6 +/- 2.2 vs 7.7 +/- 2.0 days, respectively, p = 0.43). CONCLUSIONS: Ventricular rate control occurs more rapidly with intravenous diltiazem than digoxin in AF after coronary artery bypass graft surgery. However, 12- and 24-hour response rates and duration of postoperative hospital stay associated with the two drugs are similar.

Aged↗
PubMed1998

Atrial fibrillation after bypass surgery: does the arrhythmia or the characteristics of the patients prolong hospital stay?

STUDY OBJECTIVES: The goal of this study was to determine whether prolonged hospital stay associated with atrial fibrillation or flutter (AF) after coronary artery bypass graft (CABG) surgery is attributable to the characteristics of patients who develop this arrhythmia or to the rhythm disturbance itself. DESIGN: An investigation was conducted through a prospective case series. SETTING: Patients were from a single urban teaching hospital. PARTICIPANTS: Consecutive patients undergoing isolated CABG surgery between December 1994 and May 1996 were included in the study. INTERVENTIONS: No interventions were involved. RESULTS: Of 436 patients undergoing isolated CABG surgery, 101 (23%) developed AF. AF patients were older and more likely to have obstructive lung disease than patients without AF, but both patients with and without AF had similar left ventricular function and extent of coronary disease. ICU and hospital stays were longer in patients with AF. Multivariate analysis, adjusted for age, gender, and race, demonstrated that postoperative hospital stay was 9.2+/-5.3 days in patients with AF and 6.4+/-5.3 days in patients without AF (p<0.001). CONCLUSIONS: Although AF is strongly associated with advanced age, most of the prolonged hospital stay appears to be attributable to the rhythm itself and not to patient characteristics.

Aged↗
PubMed1996

Disposition of procainamide in patients with chronic congestive heart failure receiving medical therapy.

Dosage reduction of procainamide has been recommended in patients with congestive heart failure (CHF). However, these recommendations are based primarily on studies with unmatched control groups, suboptimal blood sampling, and in patients not receiving angiotensin-converting enzyme (ACE) inhibitors. These agents increase renal blood flow, which theoretically may offset alterations in drug disposition in patients with CHF. The pharmacokinetics of procainamide in patients with chronic CHF and in matched controls were compared. A single intravenous dose of 750 mg of procainamide was administered to 9 patients with chronic New York Heart Association (NYHA) class II or III CHF (mean +/- SD left ventricular ejection fraction 22 +/- 9%) receiving medical therapy and 7 control subjects matched for age and gender. Blood and urine samples were collected at intervals over a period of 48 and 72 hours, respectively. Patients with CHF and control subjects were demographically similar, with the exception of concomitant medications, including ACE inhibitors (8/9 versus 1/7, respectively). There were no significant differences between patients with CHF and control subjects in mean +/- SD peak serum concentrations (Cmax), area under the serum concentration-time curve (AUC0-infinity), total clearance, renal clearance, half-life (t1/2), or volume of distribution (Vd) of procainamide. Similarly, there were no significant differences between patients with CHF and control subjects in the mean +/- SD Cmax, AUC0-infinity, renal clearance, or t1/2 of N-acetylprocainamide (NAPA). Procainamide dosage reduction may not be necessary in patients with chronic stable CHF who are receiving medical therapy.

Adult↗
PubMed1996

Antifibrillatory effect of esmolol alone and in combination with lidocaine.

The primary objective of this study was to determine the effect of esmolol, administered alone and in combination with lidocaine, on ventricular fibrillation threshold (VFT) in pigs. A secondary objective was to determine the relationship between blood esmolol concentrations and VFT. We determined VFT using a train of electrical stimuli delivered to the right ventricle after eight paced beats at a basic cycle length of 285 ms. Current was increased in 2-mA increments until VF occurred. VFT determinations were performed during administration of esmolol 1,000 mu g/kg/min, during a continuous infusion of lidocaine, and during infusion of esmolol and lidocaine in combination. Mean increases in VFT from baseline during infusion of esmolol and lidocaine alone were 32.3 +/- 12.9 and 8.5 +/- 7.2 mA, respectively (p < 0.05, each drug compared with baseline; p < 0.05, esmolol vs. lidocaine). Mean increase in VFT from baseline during infusion of the combination was 52.0 +/- 22.0 mA (p < 0.05 as compared with baseline and with esmolol or lidocaine alone). The relationship between blood esmolol concentrations and VFT was described by a counterclockwise hysteresis curve, suggesting delay in equilibration of esmolol between blood and site of effect. The antifibrillatory efficacy of esmolol is significantly greater than that of lidocaine in this model. Administration of the two agents in combination resulted in significantly greater antifibrillatory efficacy than that associated with either drug administered alone.

Adrenergic beta-Antagonists↗
PubMed1996

Comparison of fluorescence polarization immunoassay with liquid chromatography for quantification of procainamide and N-acetylprocainamide in urine.

The objective of this study was to compare the precision and accuracy of fluorescence polarization immunoassay (FPIA) with high-performance liquid chromatography (HPLC) for measurement of procainamide (PA) and N-acetylprocainamide (NAPA) concentrations in urine. To determine the correlation between FPIA and HPLC, urine PA and NAPA concentrations were assayed using both techniques in samples obtained from study patients receiving PA and in spiked samples. In samples from patients, FPIA-determined PA and NAPA concentrations were 19 +/- 9% lower and 28 +/- 31% higher, respectively, than those determined by HPLC. The slope of the FPIA-HPLC regression lines for PA and NAPA differed significantly from that of the line of unity (the slope that would result if FPIA and HPLC yielded identical concentrations). In spiked samples, FPIA-determined PA and NAPA concentrations were 15 +/- 2% and 11 +/- 2% lower than HPLC-determined concentrations, respectively, and the slopes of the FPIA-HPLC regression lines differed significantly from the line of unity. Therefore, FPIA cannot be recommended as a urine assay method when quantitative assessment of urine PA or NAPA excretion is needed for pharmacokinetic studies.

Acecainide↗
PubMed1995

Risk factors for the development of specific noncardiovascular adverse effects associated with amiodarone.

Noncardiovascular adverse effects associated with amiodarone result in substantial morbidity. Adverse effects involving the skin, liver, thyroid, and lungs have been reported in as many as 57%, 55%, 11%, and 13% of patients, respectively. Although risk factors for some amiodarone-induced adverse effects have been identified, risk factors for these specific side effects have not been systematically evaluated. Therefore, risk factors for development of amiodarone-induced dermatologic, hepatic, thyroid, or pulmonary adverse effects were identified using univariate analysis in 44 patients receiving the drug for supraventricular or ventricular arrhythmias (mean duration of therapy 99.5 +/- 110.8 weeks). Dermatologic side effects occurred in 4 (9.1%) patients. Patients who experienced dermatologic side effects were younger than patients who did not (mean age, 48.3 +/- 15.8 years versus 60.1 +/- 9.5 years, respectively; P = .03). Patients younger than 60 years of age were more likely to develop photosensitivity or blue-gray skin discoloration than those aged 60 or older (P = .05). Hepatic adverse effects occurred in 3 (6.8%) patients. Left ventricular ejection fraction was lower in those who developed hepatic adverse effects than in those who did not (15.0 +/- 4.0% versus 39.1 +/- 13.9%, P = .005). Adverse thyroid effects occurred in 6 (13.6%) patients; and pulmonary fibrosis occurred in 2 (4.5%) patients. No specific risk factors for adverse thyroid effects or pulmonary fibrosis were revealed. In conclusion, age less than 60 may be a risk factor for amiodarone-induced dermatologic adverse effects, whereas severely depressed left ventricular ejection fraction may be a risk factor for hepatic side effects associated with amiodarone.

Adult↗
PubMed1995

Inhibition of N-acetylation of procainamide and renal clearance of N-acetylprocainamide by para-aminobenzoic acid in humans.

Procainamide administration often results in excessively high serum N-acetylprocainamide (NAPA) concentrations and subtherapeutic serum procainamide concentrations. Inhibition of N-acetylation of procainamide may prevent accumulation of excessive NAPA while maintaining therapeutic serum procainamide concentrations. The purpose of this randomized, two-way crossover study was to determine if para-aminobenzoic acid (PABA) inhibits N-acetylation of procainamide in healthy volunteers. Eleven (7 female, 4 male) fast acetylators of caffeine received, in random order, PABA 1.5 g orally every 6 hours for 5 days, with a single intravenous dose of procainamide 750 mg administered over 30 minutes on the third day, or intravenous procainamide alone. Blood samples were collected during a 48-hour period after initiation of the infusion. Urine was collected over a 72-hour period. Serum procainamide and NAPA concentrations were analyzed using fluorescence polarization immunoassay. Urine procainamide and NAPA concentrations were measured with high performance liquid chromatography. PABA did not significantly influence total or renal procainamide clearance, elimination rate constant, AUC0-00, amount of procainamide excreted unchanged in the urine, or volume of distribution. However, concomitant PABA administration with procainamide resulted in increases in NAPA AUC0-00 and t1/2 and reductions in NAPA Ke, procainamide acetylation (NAPA formation) clearance, and NAPA renal clearance. Although PABA inhibits metabolic conversion of procainamide to NAPA, it also impairs the renal clearance of NAPA (but not procainamide) in healthy subjects. Therefore, PABA may not be useful for optimizing the safety of efficacy of procainamide in patients.

4-Aminobenzoic Acid↗
PubMed1995

Proarrhythmic effects of intravenous vasopressors.

OBJECTIVE: To review the electrophysiologic properties and the in vitro, ex vivo, animal, and human data regarding proarrhythmic effects of intravenous vasopressors. DATA SOURCES: A comprehensive (MEDLINE) search (1960-1994) was conducted for dopamine, epinephrine, norepinephrine, phenylephrine, and methoxamine. STUDY SELECTION: In vitro and ex vivo studies and investigations performed in animals or humans reporting electrophysiologic and/or proarrhythmic effects of the above intravenous vasopressors were selected. A comprehensive search of all human studies involving these agents was conducted to reveal any proarrhythmic effects that may have been reported. In addition, case reports of proarrhythmic effects associated with these agents were reviewed. DATA EXTRACTION: Data regarding electrophysiologic and proarrhythmic effects of these agents were extracted from in vitro, ex vivo, animal, and human studies. Because few studies with the specific purpose of investigating proarrhythmic effects of vasopressors have been performed in humans, all studies involving these drugs for evaluation of hemodynamic effects, clinical efficacy, or other endpoints in humans were reviewed. In addition, data were extracted from case reports of proarrhythmic effects associated with these agents. DATA SYNTHESIS: Dopamine increases automaticity in Purkinje fibers and has a biphasic effect on action-potential duration. Dopamine has caused both atrial and ventricular tachyarrhythmias in animals. Human data have revealed dose-related sinus tachycardia, with few reports of clinically significant ventricular arrhythmias. Epinephrine shortens sinus cycle length, increases atrial and ventricular automaticity, promotes atrioventricular nodal conduction, and decreases ventricular effective refractory period (ERP). It is well known to induce ventricular fibrillation and decrease the ventricular fibrillation threshold (VFT) in ex vivo models as well as intact animals. In humans, epinephrine may cause dose-related sinus tachycardia, supraventricular arrhythmias, or, more commonly, ventricular arrhythmias. Norepinephrine increases automaticity of the sinoatrial node, atria, and ventricles; promotes atrioventricular nodal conduction; and decreases ventricular ERP. In vitro/ex vivo and animal data have shown that norepinephrine significantly decreases VFT. Although electrophysiologic studies suggest that norepinephrine may be proarrhythmic, few supporting data exist in humans. Phenylephrine demonstrates differential electrophysiologic effects in atrial and ventricular tissue. Most data suggest that phenylephrine causes prolongation of the ventricular ERP. Rather than being proarrhythmic, phenylephrine may be protective against arrhythmias. The drug elevates VFT in dogs. In humans, phenylephrine effectively terminates supraventricular tachycardias and may be protective against ventricular arrhythmias. Like phenylephrine, methoxamine elevates the repetitive extrasystolic, atrial, and ventricular fibrillatory thresholds. Methoxamine also may have antiarrhythmic effects because of alpha-receptor stimulation and reflex vagal activity. Despite the relatively low risk of arrhythmogenicity associated with intravenous vasopressors, patients should be monitored for potential proarrhythmic effects and appropriate action taken as necessary. Critically ill patients often have concurrent conditions, electrolyte disturbances, and underlying arrhythmias that predispose them to a higher risk of vasopressor proarrhythmic effects. CONCLUSIONS: Controlled data supporting the proarrhythmic potential of intravenous vasopressors in humans are lacking. Sinus tachycardia, asymptomatic ventricular ectopic activity, and other ventricular or supraventricular arrhythmias have been reported in association with dopamine and epinephrine. Phenylephrine and methoxamine have been associated with sinus bradycardia, but otherwise may be antiarrhythmic. Intravenous vasopressors appear relatively safe w

Animals↗
PubMed1993

Efficacy of class 1C antiarrhythmic agents in patients with inducible ventricular tachycardia refractory to therapy with class 1A antiarrhythmic drugs.

The efficacy of class 1C antiarrhythmic agents was determined in 36 patients with inducible sustained monomorphic ventricular tachycardia during baseline electrophysiology study (EPS), who continued to have inducible monomorphic ventricular tachycardia during EPS on class 1A antiarrhythmic therapy. Of 12 patients who partially responded to class 1A drugs, 11 (91.7%) continued to have a partial response during EPS on class 1C therapy, whereas one patient did not respond. Of 24 nonresponders to class 1A therapy, 2 (8.3%) responded during EPS on class 1C therapy, 7 (29.2%) partially responded, and 15 (62.5%) did not respond. In the 24 nonresponders to class 1A therapy, 9 of 17 patients (53%) with left ventricular ejection fraction (EF) > or = 30% responded or partially responded to class 1C therapy, compared with none of 7 patients with EF < 30% (P < .05). The EPS on class 1C agents in patients who fail to respond to class 1A therapy may be warranted only in those with EF > or = 30%.

Adult↗
PubMed1992

Acute hemodynamic effects of digoxin alone or in combination with other vasoactive agents in patients with congestive heart failure.

Although digitalis preparations have been in use for greater than 200 years, it is only within the last 2 decades that the central hemodynamic and neurohumoral effects occurring over several hours following intravenous administration of digoxin have been investigated in patients with congestive heart failure (CHF). Although digoxin has been shown to stimulate myocardial contractility in tissue preparations, its positive inotropic activity does not consistently translate into improvements in hemodynamic measurements in humans. Digoxin given intravenously results in increased cardiac index and decreased heart rate, left ventricular filling pressure, and right atrial pressure, as well as in acute attenuation of neurohumoral abnormalities, in patients with chronic CHF who have abnormal baseline hemodynamic measurements. Unlike other drugs with positive inotropic activity, however, digoxin does not influence hemodynamics in normal volunteers or in CHF patients in whom hemodynamics have been normalized with other therapies. These differing effects may be related to the drug's diverse peripheral vascular effects in CHF patients in whom vasodilation may occur in comparison with those that occur in normal subjects in whom the peripheral vasoconstrictor effects may prevent the inotropic effects of the drug from being translated into an increase in cardiac output. The hemodynamic effects of digoxin in patients with chronic CHF due primarily to diastolic dysfunction have not been fully investigated. Intravenous digoxin produces hemodynamic effects in patients with CHF associated with acute myocardial infarction, but these changes are small compared with those resulting from the administration of dobutamine. Digoxin does not appear to influence hemodynamic measurements in patients with right ventricular dysfunction unless concomitant left ventricular failure is present. In patients with chronic left ventricular dysfunction, the hemodynamic effects of intravenous digoxin and vasodilators are enhanced when these agents are given in combination.

Cardiotonic Agents↗
PubMed1992

Relationship between serum concentration and dose of valproic acid during monotherapy in adult outpatients.

The relationship between serum concentration and dose of valproic acid (VPA) is reported to be variable and inconsistent. However, studies evaluating this relationship have included individuals of varying ages and patients receiving potentially interacting medications. In this study, the relationship between VPA serum concentration and dose was evaluated in a homogeneous patient population. Medical records of 60 adult outpatients with epilepsy receiving VPA monotherapy were examined retrospectively for VPA dose (milligrams per kilogram) and corresponding serum VPA concentrations. A significant linear correlation was found in the relationship between VPA dose and serum concentration among all patients (r = 0.63; p less than 0.01). However, considerable interindividual variability in this ratio was demonstrated [coefficient of variation (CV) = 28.9%], and the ratio was significantly dependent on VPA dose. In three selected individual patients, a significant linear correlation was also demonstrated in the VPA serum concentration:dose relationship over time (r = 0.91, 0.94, 0.96; p less than 0.05 for all three patients) with substantially less variability (CV = 10.2-14.6%) and without significant dose dependency, suggesting that this parameter may be useful for guiding VPA dosage adjustment and monitoring patient compliance. Further study is required to evaluate the utility of the serum concentration:dose ratio in monitoring VPA therapy.

Adult↗