Letter: Volume of distribution of quinidine.
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Humans↗
Biomedical subjects
M S Chow
Publications and source records attributed to M S Chow.
A method for determining the pharmacokinetics of endogenous creatinine without exogenous creatinine administration.
A method for determining the individual pharmacokinetics of endogenous creatinine is derived and applied in 10 post-renal transplant patients. All patients had rapidly decreasing serum creatinine concentrations (C), but relatively constant creatinine clearance (Clcr) during the study period. Based on the multiple consecutive Clcr and the corresponding C, the elimination rate constant (K), volume of distribution (V), and daily creatinine production rate (R) for each patient were derived. The creatinine 'normal' t1/2 (corresponding to a Clcr of 120 ml min-1) was also calculated. In the 10 patients studied, the observed Clcr ranged from 29.5 to 72.7 ml min-1. The corresponding calculated mean K was 0.076 +/- 0.028 h-1; R was 20.0 +/- 5.7 mg kg-1 day-1, and V was 0.60 +/- 0.1 1 kg-1. The 'normal' t1/2 was 4.0 +/- 0.93 h. These pharmacokinetic parameters are consistent with those derived from radiotracer studies and other methods reported in the literature. The present study shows that the individual endogenous creatinine pharmacokinetics can be determined by a relatively simple and noninvasive method in certain selected patients if the appropriate serum and urinary creatinine concentrations are obtained.
Creatinine↗
Pharmacokinetic data and drug monitoring: I. Antibiotics and antiarrhythmics.
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Administration, Oral↗
Mexiletine in the treatment of recurrent ventricular tachycardia. Prediction of long-term arrhythmia suppression from acute and short-term response.
Acute intravenous and short-term oral mexiletine therapy was effective in suppressing the arrhythmia in six of eight patients with recurrent ventricular tachycardia. Five of the six patients who were placed on maintenance therapy remained asymptomatic during a mean follow-up of 15 months. The study shows that the acute and short-term suppression of ventricular tachycardia by mexiletine can be a useful predictor of its long-term efficacy.
Aged↗
Terbutaline infusion in cardiogenic shock: acute hemodynamic effects and clinical response.
The effect of terbutaline infusion was studied in six patients with cardiogenic shock due to acute myocardial infarction. Terbutaline was initiated at 3 micrograms/kg/min, and the subsequent infusion rate was adjusted according to heart rate and blood pressure. At 3 hours after infusion arterial pressure increased from 62 +/- 13 mm Hg (mean +/- S.D.) to 89 +/- 13 mm Hg (P less than 0.001), cardiac index increased from 1.38 +/- 0.29 liter/min/m2 to 2.68 +/- 0.47 liter/min/m2 (P less than 0.001), and heart rate increased from 92 +/- 32 beats/min to 112 +/- 29 beats/min (P less than 0.005). Pulmonary artery wedge pressure fell from 24 +/- 7 mm Hg to 17 +/- 3 mm Hg (P less than 0.01), right atrial pressure fell from 12 +/- 4 mm Hg to 6 +/- 3 mm Hg (P less than 0.005), and systemic vascular resistance fell from 1880 +/- 641 dyn-sec/cm5 to 1515 +/- 418 dyn-sec/cm5 (P less than 0.05). In addition, urine flow increased from 4 +/- 6 ml/hr to 314 +/- 237 ml/hr (P less than 0.05), and subjective improvement was noted in all subjects. Undesirable effects observed were hypokalemia (all subjects), supraventricular tachycardia (one subject), and ventricular ectopic beats (three subjects), which responded to potassium replacement and other treatments. All patients required prolonged maintenance infusion to maintain adequate hemodynamic and clinical response. Four patients were weaned off from maintenance therapy after a mean duration of 4.8 days and eventually were discharged from the hospital.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Myocardial metabolic effects of intravenous terbutaline in patients with severe heart failure due to coronary artery disease.
Intravenous terbutaline, 0.3 mg/kg/min for 30 minutes followed by 0.15 mg/min for 60 minutes, was studied in nine patients with severe heart failure due to documented coronary artery disease. Hemodynamic and myocardial metabolic effects were measured during terbutaline infusion. Cardiac index and stroke index increased, whereas mean pulmonary artery wedge pressure and pulmonary vascular resistance decreased significantly. No significant alterations in aortic oxygen content, coronary sinus oxygen content, myocardial oxygen extraction, and myocardial lactate extraction were observed during terbutaline infusion. No patient developed angina or electrocardiographic changes suggestive of ischemia. These results indicate that intravenous terbutaline infusion, at the dosage employed, produces beneficial hemodynamic effects without a deterioration of myocardial metabolism in patients with heart failure due to coronary artery disease.
Aged↗
Oxytocin and an oxytocin agonist administered centrally decrease food intake in rats.
Intracerebroventricular administration of oxytocin (OT) and an OT agonist significantly decreased food intake in a dose-related manner in fasted rats. Central administration of an OT antagonist by itself (up to doses of 8 nmol) did not potentiate deprivation-induced food intake, but pretreatment with the OT receptor antagonist prevented the expected inhibition of food intake produced by OT and the OT agonist. Once-daily ICV injections of OT led to the development of tolerance to the inhibitory effects on food intake by the third day of treatment, but daily pretreatment with the OT antagonist prevented the development of this tolerance. In addition to causing decreased food intake, ICV administration of OT significantly increased grooming behavior but produced no dyskinesias. The inhibitory effect of OT on food intake was characterized by decreased amounts of food intake but a normal pattern of ingestion. The anorexia produced was central in nature and was not associated with altered plasma levels of hormones involved in caloric homeostasis or with changes in blood glucose. The OT agonist had relatively little effect on water intake when given in doses that significantly inhibited food intake. These results support the hypothesis that specific OT receptors within the central nervous system participate in the inhibition of feeding under certain conditions in rats.
Angiotensin Receptor Antagonists↗
Predicting plasma procainamide concentrations resulting from a sustained-release preparation.
Two methods of predicting plasma procainamide concentrations (PPCs) for a sustained-release procainamide (SRP) dosage form were compared using previously published data on 12 healthy subjects. Methods A and B were both based on a one-compartment pharmacokinetic model requiring an elimination rate constant and area under the concentration-time curve from an immediate-release oral procainamide dosage form and in vitro dissolution data from the SRP product. Method A also used an absorption rate constant. The predicted versus measured PPCs for two sets of peak and trough concentrations in each subject were evaluated using linear regression. The mean predicted PPCs by both methods followed the measured PPCs closely; however, the time of peak concentration was predicted more accurately by method A. The evaluation of predictive performance showed good precision and a small but statistically significant bias with either method, peak values were overpredicted and trough values were underpredicted. These two methods adequately predicted plasma procainamide concentrations in healthy subjects following a sustained-release procainamide preparation.
Delayed-Action Preparations↗
Comparison of four methods of predicting serum gentamicin concentrations in adult patients with impaired renal function.
Four methods of predicting serum gentamicin concentrations (SGCs) in adult patients with stable impaired renal function were compared. Serum samples obtained from 17 patients receiving intravenous gentamicin therapy were assayed for gentamicin using a radioimmunoassay. Kinetic variables derived using four different methods were used to predict peak and trough concentrations. The Sawchuk-Zaske method uses individualized apparent volume of distribution (Vapp) and half-life (t1/2) derived from at least three SGCs following a given dose. The fitted method assumes Vapp equals 0.28 liters/kg lean body weight (LBW) and a t1/2 derived by a fitting technique using only one SGC. Both the Tozer and Hull methods assume Vapp equals 0.28 liters/kg LBW, and t1/2 is estimated from equations that take into account the patient's renal function (creatinine clearance). The predicted and measured SGCs for each method were compared using linear regression analysis. The prediction errors, defined as the predicted minus the measured SGC, were compared for the four methods. The correlation coefficients between the measured and predicted SGCs were significant at p less than 0.05 only for the Sawchuk-Zaske and fitted methods. For the Sawchuk-Zaske method, peak and trough r values were 0.73 and 0.91, respectively. For the fitted method, peak and trough r values were 0.53 and 0.71, respectively. No significant differences in the mean prediction errors were observed, except for the Sawchuk-Zaske method, which had significantly less mean prediction error than the Hull method. The Sawchuk-Zaske method was the most reliable and accurate pharmacokinetic technique. However, because it is more costly and less convenient than the other three methods, both the accuracy and cost should be considered when selecting a method for determining serum gentamicin concentrations for a particular patient.
Aged↗
Assessing the treatment of congestive heart failure: diuretics, vasodilators, and angiotensin-converting enzyme inhibitors.
Congestive heart failure (CHF) causes disabling symptoms and increases the likelihood of decreased survival. Diuretics, direct vasodilators, and angiotensin-converting enzyme (ACE) inhibitors can be used to reduce symptoms, prolong life, or both, in these individuals. Diuretics induce sodium and water excretion, leading to decreased cardiac preload and wall tension, and an effective decrease of symptomatic pulmonary and systemic congestion. They have not yet been shown to prolong life in patients with CHF, however. Direct vasodilators, which induce venodilation, arterial dilation, or both (balanced vasodilators), may improve symptoms, and some but not all prolong life. Venodilators, such as nitrates, exert a venous pooling effect, decreasing cardiac preload and symptoms of congestion. Arterial dilators, such as hydralazine, decrease afterload and improve cardiac output. The combination of hydralazine and isosorbide dinitrate provides balanced vasodilation. It also improves survival, but is associated with a relatively high frequency of side effects necessitating discontinuation of one or both agents. The drugs are not approved by the Food and Drug Administration for the treatment of heart failure. Flosequinan, a new orally administered, long-acting, balanced arteriovenous dilator, improves exercise tolerance and symptoms. However, preliminary analysis of data from a large, multicenter trial revealed increased mortality and hospitalization for worsening CHF. The drug has recently been withdrawn from the market. The ACE inhibitors can cause hemodynamic and neurohormonal changes that lead to a reduction of preload and afterload, decreasing symptoms of heart failure. They significantly decrease CHF mortality, and might also deter the development of overt heart failure in some asymptomatic patients with left ventricular dysfunction.
Angiotensin-Converting Enzyme Inhibitors↗
Advanced cardiac life support controversy: where do antiarrhythmic agents fit in?
Approximately half of all cardiovascular fatalities are attributable to sudden cardiac death, and the majority of sudden cardiac deaths result from ventricular fibrillation (VF). Antiarrhythmic agents are needed to manage refractory VF and ventricular tachycardia (VT); the primary reason for their administration is to prevent recurrence of VF and to abolish VT. The American Heart Association recommends lidocaine hydrochloride as a first-line antiarrhythmic agent in the advanced cardiac life support (ACLS) setting, followed by bretylium tosylate. Although the newly approved intravenous antiarrhythmic agent, amiodarone hydrochloride, may potentially be effective in ACLS, studies are needed to document its clinical benefit in this setting. Such studies are currently under way to document this potential use.
Amiodarone↗
The pharmacokinetics of intravenous estradiol--a preliminary study.
Estradiol USP was extemporaneously compounded for intravenous administration. Eight postmenopausal women were randomized to receive one of four estradiol dosages. Serum estradiol concentrations were determined at frequent intervals after single bolus dosing. The concentration-time profile was stripped and fit, and pharmacokinetic values were generated. Approximate dosage proportionality was seen with area under the curve, the terminal half-life was 27.45+/-5.65 minutes, and volume of distribution was very low (0.082+/-0.015 L/kg). Estradiol was well tolerated by all study participants.
Aged↗