Search PubMed⌕ Search

Biomedical subjects

J R Koup

Publications and source records attributed to J R Koup.

At least 91 records · Page 5Linked to original sources
PubMed1977

Paradoxical behavior of serum digoxin concentrations in an anuric neonate.

Serum digoxin values were determined in a newborn infant with severe heart failure and renal failure. The half-life of digoxin in the serum appeared to change, possibly the result of prolonged distribution and/or absorption owing to circulatory insufficiency, or to the accumulation of cross-reacting metabolites of digoxin in the serum. No clinical toxicity was apparent, and no cardiac arrhythmia was observed. The need for monitoring serum digoxin concentration and clinical effect in newborn infants is emphasized.

Anuria↗
PubMed1977

Intravenous theophylline therapy: nomogram guidelines.

We evolved a nomogram for guiding and standardizing intravenous theophylline therapy in hospitalized patients. It provides rapid calculation of a loading dose based on body weight and previous therapy and a maintenance infusion rate related to three categories of expected metabolic activity. The guidelines were prospectively used in the treatment of 72 patients, mainly in a respiratory care unit. The nomogram was successfully used to attain near-steady-state serum concentrations in the therapeutic range of 8 to 20 mg/litre in 72% of patients, with only two patients outside of the range of 5 to 25 mg/litre. These guidelines facilitate initial theophylline dosage in older patients with liver and cardiac disease and provide a rational basis for interpreting serum concentration measurements and adjustment of drug therapy.

Adult↗
PubMed1976

Theophylline pharmacokinetics in premature infants with apnea.

The pharmacokinetics of theophylline were examined in eight low-birth-weight infants (gestation: 26-32 weeks: birth-weight: 887-1,480 gm), who received the drug for treatment of primary apnea. The drug was assayed by high pressure liquid chromatography. The final dosage was 1 to 3 mg/kg/6 hour at 25 to 37 days of age. At the time, theophylline had a prolonged half-life ranging from 13 to 29 hours, a relatively large volume of distribution of 0.65 to 2.86 1/kg, and a small body clearance of 23 to 68 ml/hr/kg. The extremely slow and variable elimination of theophylline must be considered in treatment of apneic infants. The initial dosage regimen suggested is a loading dose of 6 mg/kg and a maintenance dose of 2 mg/kg/ 12 hours, with adjustments made based on monitoring of the serum concentration and on an increased biotransformation capability as maturation occurs.

Apnea↗
PubMed1976

System for clinical pharmacokinetic monitoring of theophylline therapy.

A system was developed for guiding theophylline therapy in acutely ill patients with respiratory disease and for recovery of pharmacokinetic information. A dosage regimen nomogram was designed based on literature data and preliminary pharmacokinetic studies in patients. Using the nomogram, physicians select the loading and infusion dosages based on previous therapy, body weight, age, and cardiac and hepatic status of the patient. Specifications are provided for loading (up to 5.6 mg/kg) and maintenance doses (0.9, 0.68, or 0.45 mg/kg/hr) of aminophylline, handling of i.v. dosage forms, and collection of three initial blood samples. Serum samples were assayed for theophylline by high-performance liquid chromatography for rapid feedback of data to the physician and computer estimation of body clearance values. The usefulness of the nomogram guidelines was examined prospectively in 72 patients. Near-steady-state serum concentrations in the therapeutic range of 8-20 mg/liter were found in 72% of the patients. Only two patients were outside of the range of 5-25 mg/liter. The relationship between the physician's estimate of the patient's clinical status (three classes) and measured body clearance was highly significant (p less than 0.025). A comprehensive data collection format allows further analysis of the factors responsible for the variability in theophylline disposition in patients undergoing therapy.

Adult↗
PubMed1975

Digoxin pharmacokinetics: role of renal failure in dosage regimen design.

Radioimmunoassayed serum concentration and urinary excretion data for digoxin from azotemic patients were characterized using a 2-compartment open model. Urinary excretion rates of digoxin as well as serum concentration data are needed to accurately characterize the disposition of the drug. Seven patients with renal failure showed highly variable steady-state volumes of distribution (V-ss-D equals 195 to 489 liters/1.73 m-minus2) and t1/2beta values (1.5 to 5.2 days). This variability is a major limiting factor in the use of dosage regimen nomograms that assume a constant V-ss-D and a rigorous relationship between t1/2beta and creatinine clearance (Cl-CR). Body clearance (Cl-B) is a parameter that is affected by both elimination and distribution of drugs. A linear relationship between Cl-B and renal clearance of digoxin or Cl-CR was found and was used to develop a model-independent approach to calculation of maintenance doses of digoxin. Several methods for calculating steady-state serum concentrations of digoxin (C-ss-p) were compared with actual measurements obtained in 16 chronically medicated patients. Optimum computation of C-ss-p is obtained by use of digoxin renal and body clearances. Variability in the digoxin:creatinine renal clearance ratio is the major limiting factor in prediction of digoxin dosage regimens.

Adult↗
PubMed1975

pH-dependent secretion of procainamide into saliva.

The relationship between serum and stimulated, mixed saliva concentrations of procainamide was determined in 12 chronically medicated patients. Samples were obtained at times chosen to approximate the maximum and minimum serum concentrations of the drug during a dosing interval. Marked intersubject variability was found in the ratio of saliva to serum concentration of the drug (0.27-8.93). There was no correlation between the dose (milligrams per kilogram per day) and the minimum serum or saliva concentration of procainamide. Saliva pH ranged from 6.3 to 8.0 in eight subjects. The ratio of saliva to serum concentration of procainamide increased with decreasing pH. This result can be largely explained by the pH-dependent ionization and distribution of procainamide, a weak base.

Humans↗
PubMed1975

Digoxin concentrations in serum and saliva.

Serum and mixed saliva concentrations of digoxin were measured in 34 hospitalized patients. The mean saliva:serum concentration ratio of digoxin was 1.14 (plus or minus 0.48). Of 20 patients with saliva digoxin concentrations in the range of 0.7 to 1.5 ng/ml, 18 patients had serum concentrations which were within the same range. Saliva offers a convenient and noninvasive means of monitoring the digoxin status of patients.

Digoxin↗
PubMed1972

Pharmacy hours.

Explore the source record for details and available documents.

Economics↗
PubMedDate not supplied

A single and multiple dose pharmacokinetic and metabolism study of meclofenamate sodium.

A single and multiple oral dose administration study of meclofenamate sodium (Meclomen) was conducted in ten healthy male volunteers. An initial 300 mg oral dose on day 1 was followed by a 100 mg every 8 h dosage regimen on study days 4 through 18. Intensive plasma and urine sample collection was carried out over the first three study days, and for 120 h following administration of the final dose on day 18. Plasma and urine specimens were analyzed by a specific HPLC assay for unconjugated meclofenamic acid and metabolites I and II of meclofenamic acid before and after sample incubation with beta-glucuronidase. Meclofenamic acid was rapidly absorbed following oral dose administration. Concentrations of meclofenamic acid existed primarily as unconjugated drug in plasma, with only a small amount present in the conjugated form. Meclofenamic acid was rapidly eliminated, with an elimination half-life of approximately 1.3 h. This resulted in no detectable accumulation upon multiple dose administration. Metabolite I, which is one-fifth as active as meclofenamic acid in in vitro inhibition of cyclooxygenase, was present in unconjugated form at steady state in concentrations approximately 50 per cent of those of meclofenamic acid, as unconjugated drug. The majority of metabolite I in plasma existed as glucuronide conjugate. Metabolite II, which is inactive, was present in very significant concentrations in unconjugated form. Plasma protein binding determinations conducted on meclofenamic acid and metabolite I indicated that the free fraction of metabolite I was 8.7 to 10.9 times higher than that of meclofenamic acid. When the lower activity and lower steady state concentrations, but higher free fraction, are considered, it would appear that metabolite I may contribute significantly to the in vivo inhibition of cyclooxygenase activity seen after administration of meclofenamic acid.

Adult↗
PubMedDate not supplied

Haemoperfusion in the management of digoxin toxicity: is it warranted?

Several recent publications have encouraged the use of hemoperfusion to remove digoxin from the body of overdosed patients. The usefulness of haemoperfusion in removing digoxin from the body has therefore been examined using pharmacokinetic simulation techniques and published data. Haemoperfusion for a period of 4 hours with a clearance of 100 ml/min removes less than 7% of the amount of digoxin in the body (including that in the gastrointestinal tract at the beginning of haemoperfusion), regardless of the time after the dose that haemoperfusion is started. Dramatic therapeutic benefit in digoxin intoxication is unlikely to be a consequence of the amount of digoxin removed from the body by haemoperfusion. If therapeutic benefit is derived from a transient decline of digoxin concentration in plasma, it may be expected to be negated as the drug redistributes from tissues.

Digoxin↗
PubMedDate not supplied

Hypothesis for the individualisation of drug dosage.

Computer simulations based on the pharmacokinetics of chloramphenicol and theophylline in patients, indicate a very strong correlation (r = 0.988 for chloramphenicol and r = 0.971 for theophylline) between log maintenance dose required to achieve a desired average drug concentration in serum at steady-state, and the drug concentration in serum 6 hours after an initial test dose administered by constant rate intravenous infusion over 0.5h. Accordingly, we have developed a nomogram to predict individual daily dosing requirements for these drugs in uncomplicated patients from a single serum assay following an initial dose. Within defined limits, predictions made with the nomogram are essentially equivalent to those made by iraditional pharmacokinetic methods which require substantially more drug concentration-time data following a test dose. Predictions based on the nomogram are relatively unaffected by small but typical errors in magnitude of the test dose, infusion time, sampling time and assay. Protocols for the administration of the test dose other than described, e.g. administration of an oral theophylline solution, may be equally useful for dosage predictions. In principle, this approach should apply to other drugs.

Chloramphenicol↗
PubMedDate not supplied

Prediction of maintenance dose required to attain a desired drug concentration at steady-state from a single determination of concentration after an initial dose.

Strong correlations have been reported between drug concentrations at steady-state and a single drug concentration determined sometime after an initial dose for lithium, nortriptyline, imipramine, desipramine, choramphenicol and theophylline. The mathematical basis of these relationships suggests that a one point method for predicting steady-state drug concentrations and individual dosing requirements should be widely applicable to most drugs and should be valid for patients having a wide range of drug half-lives. A method is presented for evaluating the optimum time of blood sampling to determine a drug concentration in serum of plasma that best correlates with steady-state levels and for defining the range of drug half-lives beyond which the predictive approach is likely to give poor results.

Antidepressive Agents, Tricyclic↗
PubMedDate not supplied

Rapid estimation of chloramphenicol clearance in infants and children.

A method is presented by which chloramphenicol clearance (CL) can be estimated from a single serum sample obtained 6 hours after the initial intravenous dose. The method was evaluated prospectively in 20 infants and children who received intravenous chloramphenicol sodium succinate. Agreement between predicted and observed clearance was excellent (r = 0.914, p less than 0.001). The equation of the observed regression line was: observed 0.886x predicted + 0.019. The method appears to provide reasonably accurate estimates of clearance which can be used for rapid clinical adjustment of dose.

Child↗
PubMedDate not supplied

Multiple-dose non-linear regression analysis program. Aminoglycoside dose prediction.

The ability of a new multiple-dose non-linear regression analysis program to predict steady-state aminoglycoside peak and trough serum concentrations was evaluated. 30 patients receiving either amikacin (7), gentamicin (10) or tobramycin (13) were studied. A standard method of prediction which requires the collection of 3 or 4 serum samples during a dosing interval and a predictive method which relies upon population-based estimates of pharmacokinetic parameters were compared with the new approach which requires the collection of 2 serum samples. There were no significant differences between the methods which utilised serum concentration data with regard to predictive precision (mean prediction error of about 10%). These methods were more precise than the population-based method (p less than 0.01, mean prediction error 29.1%). None of the methods produced biased estimates. These results indicate that when the regression program is employed, valid estimates of pharmacokinetic parameters and prediction of steady-state serum concentrations can be obtained with fewer serum samples than have been recommended.

Adult↗