PubMed Health⌕ Search

Biomedical subjects

K J Simons

Publications and source records attributed to K J Simons.

88 records · Page 5Linked to original sources
PubMed1980

Theophylline toxicity in term infants.

The pharmacokinetics of theophylline were studied in 1-month-old term infants who received accidental overdoses of theophylline during treatment for bronchiolitis. Both infants survived without neurologic sequelae. Elimination half-life values of 14.5 and 15.2 hours, respectively, were shorter than reported in premature infants but longer than in infants aged 3 months or older. Caffeine appeared in the sera of both patients, who had not received it in any form. In term infants, elimination of theophylline may occur by N-methylation in contrast to older patients in whom the drug is chiefly eliminated by demethylation and oxidation. Theophylline has not been proved effective for the treatment of bronchiolitis. It should be used with caution for wheezing in very young infants until its pharmacokinetics have been studied further in nontoxic, full-term infants younger than age 3 months.

Bronchopneumonia↗
PubMed1979

Theophylline protein binding in humans.

Theophylline protein binding was 58-82% in serum from six normal adults and 42 asthmatic patients, 1-25 years old, who were given 5 mg of theophylline/kg. The binding range was greatest in young patients, but the proportion of protein-bound drug did not correlate with age. Theophylline protein binding was higher than previously reported. The effect of binding should be considered in patients who do not have optimal bronchodilation from theophylline despite total serum theophylline concentrations of 10-20 microgram/ml.

Adolescent↗
PubMed1979

Urinary excretion of dyphylline in humans.

The pharmacokinetics and urinary excretion of a single dyphylline dose were studied in five normal volunteers. The mean dyphylline half-life was 1.8 +/- 0.2 hr; the mean total body clearance rate and mean renal clearance rate were 333 +/- 62 and 276 +/- 52 ml/min, respectively; and the mean volume of distribution was 0.8 +/- 0.2 liter/kg. In the urine, 83 +/- 5% of the dose was excreted as unchanged drug, and theophylline was not detected. Dyphylline doses of 19--27 mg/kg, resulting in peak serum dyphylline concentrations of 19.3--23.5 micrograms/ml, were tolerated well by four subjects. One subject had a severe headache following a 28-mg/kg dose, associated with a peak serum dyphylline concentration of 36.4 micrograms/ml. This study confirms speculation that dyphylline is not metabolized to theophylline in vivo.

Adult↗
PubMed1978

Pharmacokinetics of theophylline in infancy.

Theophylline clearance rates and half-life values were measured in 15 infants aged three to 23 months, after infusion of aminophylline by the intravenous route for at least 24 hours. The mean clearance rate was 1.07 +/- 0.55 ml/min-kg, which is comparable with values obtained by others in older children. There was some correlation of clearance rates with age. The mean half-life was 4.4 +/- 2.2 hours. There was a tenfold variability in half-life, suggesting that individualization of theophylline dose is especially important in infants if undertreatment and toxicity are to be avoided.

Age Factors↗
PubMed1978

Physiologic changes induced by theophylline in the treatment of apnea in preterm infants.

Ten preterm infants (birth weight 0.970 to 2.495 kg) with apnea due to periodic breathing (apneic interval = 5 to 10 seconds) or with "serious apnea" (greater than or equal to 20 seconds) were studied before and after the administration of theophylline. We determined the incidence of apnea, respiratory minute volume, alveolar gases, arterial gases and pH, "specific" compliance, functional residual capacity, and work of breathing. Theophylline decreased the incidence of apnea (P less than .05), increased respiratory minute volume (P less than 0.001), decreased (PACO2 (and PaCO2 P less than 0.001), increased the slope of the CO2 response curve (P less than 0.02) with a significant shift to the left (P less than 0.02). These findings suggest that the decreased incidence of apnea after theophylline is associated with an increase in alveolar ventilation and increased sensitivity to CO2 with a pronounced shift of the CO2 response curve to the left. These data are consistent with the idea that apnea is a reflection of a depressed respiratory system.

Apnea↗
PubMed1978

Pharmacokinetics of theophylline in acute asthma.

Serum theophylline concentrations were measured in 17 children and adolescents with acute asthma who received an aminophylline loading dose of 7 mg/kg and a constant infusion of 15 mg/kg/24 hours. The mean total theophylline clearance rate was 1.32 +/- S.D. 0.66 ml/min/kg. Hypoxia, and in two patients, acidosis, did not appear to significantly influence theophylline clearance rates. Inter-individual differences in clearance rates were great. No child experienced symptoms or signs of theophylline toxicity during the study. If serum theophylline concentrations cannot be monitored readily, an aminophylline infusion rate of 15 mg/kg/24 hours can be used safely in patients with acute asthma, but in most patients this infusion rate will not provide serum theophylline concentrations in the desired therapeutic range of 10-20 microgram/ml. Monitoring of serum theophylline concentrations during aminophylline infusion is desirable in order to individualize infusion rates, and achieve optimal bronchodilation without toxicity.

Acute Disease↗
PubMed1977

Bioavailability of a sustained-release dyphylline formulation.

The bioavailability of dyphylline from sustained-release tablets, studied in seven normal subjects given a single dose of the drug, was 67.8 per cent of that from conventional tablets. In three subjects given 40 mg/kg dyphylline as sustained-release tablets every 8 hours for four days, serum dyphylline concentrations were maintained above 7.88 microng/ml once steady state was achieved. No adverse effects were noted, though in one subject peak serum dyphylline concentrations reached 30 microng/ml after multiple doses.

Adult↗
PubMed1975

GLC determination of procainamide in biological fluids.

A GLC method for the determination of procainamide in biological fluids is presented. By using a dipropyl analog of procainamide as an internal standard, both compounds can be chromatographed directly, yielding linear calibration curves and a sensitivity that allows quantitative determination of concentrations as low as 0.1 mug/ml. The extraction procedure was carefully modified to avoid hydrolysis of N-acetylprocainamide, a major metabolite of procainamide. The usefulness of the procedure is demonstrated by following the disappearance of procainamide from the plasma and urine of human subjects treated with the drug.

Chromatography, Gas↗
PubMed1975

The pharmacokinetics of dihydroxypropyltheophylline: a basis for rational therapy.

Dihydroxypropyltheophylline (dyphylline) was administered in a single dose on 7 different days to 7 normal subjects; 5 mg/kg was given by intramuscular injection and oral tablet; 10 mg/kg was given by these routes and also in 3 different liquid formulations. Dyphylline is rapidly absorbed, and bioavailability is independent of route of administration or formulation. The pharmacokinetics of dyphylline do not appear to be dose-dependent in the dosage range studied. The mean half-life of dyphylline is 2.11 +/- 0.36 hr; because of its short half-life and unproved efficacy, current dosage recommendations for dyphylline must be revised greatly. Further efficacy trials utilizing the pharmacokinetic data from this study are essential.

Administration, Oral↗
PubMed1975

Efficacy of dyphylline (dihydroxypropyltheophylline) in exercise-induced bronchospasm.

The efficacy of dyphlline in prevention of exercise-induced bronchospasm (EIB) was studied in seven subjects. A single 15 mg/kg dose of dyphylline 40 minutes prior to exercise prevented EIB as documented by a significantly smaller mean greatest percent decrease in forced expiratory volume in one second when compared to placebo. Mean serum dyphylline concentrations 40 minutes after a dose of 15 mg/kg were probably in the lower portion of the therapeutic range.

Adolescent↗
PubMed1975

The pharmacokinetics of procainamide in normal subjects using a specific gas chromatographic assay.

Previous procainamide pharmacokinetic studies have involved the use of colorimetric and fluorimetric methods for the determination of drug concentrations in plasma and urine. However, recent evidence shows that N-acetyl procainamide, the major metabolite in humans, is hydrolyzed during these assay procedures. As a result, a specific gas chromatographic method has been developed for the determination of procainamide in biological fluids. Using this assay procedure, the pharmacokinetics of procainamide were studied in 7 normal subjects following intravenous administration of the drug. The values of half-life (2.08 +/- 0.52 hr), volume of distribution (4.3 +/- 0.6 1/Kg) and total body clearance (1344 +/- 238 ml/min) found in this study differed from those previously reported. These discrepancies could be understood in terms of differences in assay specificity.

Blood Pressure↗
PubMedDate not supplied

The pharmacokinetics of HI-6 in beagle dogs.

The pharmacokinetics of HI-6 were studied following intravenous administration to beagle dogs (n = 7). The bioavailability of two different strength intramuscularly administered doses was also determined in the same animals. After a 20 mg kg-1 intravenous dose, the mean (+/- S.D.) initial HI-6 plasma concentration was 93.1 +/- 10.8 micrograms ml-1. The mean half-life was 48.2 +/- 17.7 min, the mean total body clearance was 5.16 +/- 0.81 ml min-1 kg-1, the mean apparent volume of distribution was 0.37 +/- 0.20 l kg-1 and 61.2 +/- 14.6 per cent of the dose was excreted as unchanged drug. The pharmacokinetic constants calculated following the 20 mg kg-1 intramuscular doses of 250 and 25 mg ml-1 solutions were not significantly different from those obtained following the intravenous dose. Also, the areas under the plasma concentration versus time curves were not significantly different indicating 100 per cent bioavailability from the intramuscular route of administration.

Animals↗
PubMedDate not supplied

Effect of poisoning by soman (pinacolyl methylphosphonofluoridate) on the serum half-life of the cholinesterase reactivator HI-6 in mice.

The effect of fasting, atropine, and poisoning by an organophosphate anticholinesterase soman (pinacolyl methylphosphonofluoridate) on the pharmacokinetics of the acetylcholinesterase oxime reactivator HI-6 (CAS Reg. No. 34433-31-3; 1-[(4-(aminocarbonyl)pyridinio)methoxy)methyl)-2-(hydroxy imino)methyl) pyridinium dichloride) was investigated. Pharmacokinetic parameters (elimination half-life, volume of distribution, clearance rate) were determined for the following groups: (1) a 20 and 50 mg kg-1 dose of HI-6; (2) a 50 mg kg-1 dose of HI-6 after fasting for 18 h (water ad lib); (3) a 50 mg kg-1 dose of HI-6 at 0, 4, and 24 h after atropine (17.4 mg kg-1, i.p.) and soman (287 micrograms kg-1, s.c.); and (4) a 50 mg kg-1 dose of HI-6 at 0 and 4 h after soman (100 micrograms kg-1, s.c.). Fasting increased significantly (p less than 0.05) the elimination of half-life (t1/2) and tended to increase the volume of distribution (Vd) and decrease the clearance rate (CL). Following soman (287 micrograms kg-1) poisoning the t1/2 of HI-6 increased from 8.6 min to 21.6 min and the Vd increased to 0.731 kg-1. At the lower soman dose (100 micrograms kg-1) no significant effect on HI-6 pharmacokinetics was found. Atropine (17.4 mg kg-1: i.p.) pretreatment increased the t1/2 and CL while having no effect on the Vd. By 24 h the pharmacokinetic parameters of HI-6 in the various treatment groups were not significantly different from the control group. The changes in the pharmacokinetics of HI-6 following soman and atropine are probably the result of haemodynamic changes.

Animals↗