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Biomedical subjects

G Koren

Publications and source records attributed to G Koren.

At least 631 records · Page 35Linked to original sources
PubMed1985

A simple method for the estimation of glomerular filtration rate by gentamicin pharmacokinetics during routine drug monitoring in the newborn.

Assessment of the glomerular filtration rate (GFR) in the newborn is often imprecise because of difficulties in urine collection and because the plasma creatinine level, the traditional marker of renal function, is influenced by many factors in this age group. Gentamicin is given to most preterm infants for suspected or proved sepsis. This drug is eliminated almost entirely by the kidney and its rate of elimination parallels the GFR. We calculated gentamicin pharmacokinetic parameters (t1/2, volume of distribution, and clearance) from three consecutive concentration-time points (trough, peak, and next trough levels) in 38 newborn infants. Creatinine clearance was measured by the conventional method. Both t1/2 (r = 0.74; P less than 0.001) and gentamicin clearance (r = 0.77; P less than 0.001) correlated well with measured creatinine clearance. There was no correlation between these variables and urine output. Gentamicin elimination t1/2 and clearance are useful indices of GFR in the newborn infant and can be easily calculated during routine therapeutic drug monitoring.

Creatinine↗
PubMed1985

Influence of hypothermia on the pharmacokinetics of gentamicin and theophylline in piglets.

The influence of hypothermia on gentamicin and theophylline pharmacokinetics was studied in anesthetized pigs given an iv bolus of gentamicin and theophylline during normothermia (37 degrees C) and again 1 wk later after the induction of controlled hypothermia (29 degrees C). During hypothermia, the elimination half-time for gentamicin was significantly prolonged (135 +/- 19 min at 37 degrees C vs. 187 +/- 7 min at 29 degrees C), and there were significant decreases in the volume of the central compartment (Vc) of gentamicin, the gentamicin volume of distribution (Vd), and the gentamicin total body clearance (TBC). Hypothermia was associated with a small but significant decrease in theophylline Vd and Vc, but no change in TBC. In separate experiments, cardiac output decreased during the induction of hypothermia in a temperature-dependent fashion. The changes in gentamicin Vd and TBC may be explained by the decrease in cardiac output and the associated decrease in glomerular filtration rate. This study suggests that the elimination of theophylline, which has a relatively low hepatic extraction ratio, is not influenced by the hypothermia-induced decrease in liver blood flow.

Animals↗
PubMed1985

Organization and efficacy of a therapeutic drug monitoring consultation service in a pediatric hospital.

On July 1, 1982, a therapeutic drug monitoring (TDM) consultation service was instituted in the hope of improving the decision-making of clinicians with respect to drug therapy. Thirteen different drugs are monitored daily, with an average load of 1,600 inpatient samples per month. The team consists of clinical pharmacology fellows and staff who are available 7 days a week to monitor all drug levels that are outside the putative therapeutic range. In order to evaluate the efficacy of this service in preventing development of potentially toxic drug concentrations, the TDM data from July 1982 to December 1983 have been reviewed. The percentage of toxic levels from the total sample load was significantly lower in the period of July-December 1983 compared with July-December 1982 at the beginning of the service (2.25% vs. 4.25%, p less than 0.01). Since January 1983, the percentage has been maintained at less than 3%. A TDM consultation service can help to optimize the use of drug monitoring data by physicians and may lead to improved prescribing in a hospital setting.

Adolescent↗
PubMed1985

Coexistence of Kaposi's sarcoma and chronic lymphocytic leukemia in the same lymph node.

A patient with chronic lymphocytic leukemia in whom a carcinoma of the gall bladder was previously found is described. The patient was treated with prednisone and chlorambucil and developed a significant lymphadenopathy. A biopsy of one of the lymph nodes revealed the coexistence of Kaposi's sarcoma and chronic lymphocytic leukemia in the same node. This and the presence of three malignancies in the same patient are discussed.

Aged↗
PubMed1985

Fentanyl pharmacokinetics and hemodynamic effects in preterm infants during ligation of patent ductus arteriosus.

A bolus of 30 micrograms X kg-1 fentanyl was given to nine preterm infants (gestational age 31.8 +/- 4.7 weeks, weight 1100 +/- 309 g) for induction of anesthesia for ligation of a patent ductus arteriosus. Thirty minutes after the injection, fentanyl plasma concentrations were between 7.7 and 13.6 ng X ml-1. Elimination half-life was 6-32 hr (mean +/- SD, 17.7 +/- 9.3). Systolic blood pressure remained stable throughout surgery. There was a gradual increase in heart rate from 159 +/- 12 min-1 at the time of skin incision to 173 +/- 15 min-1 at the time of skin closure (P less than 0.05). Fentanyl plasma concentrations remained virtually unchanged between 30 min (10.6 +/- 1.9 ng X ml-1) and 120 min (9.6 +/- 1.6 ng X ml-1); whereas at the end of surgery most infants moved and breathed spontaneously. This phenomenon can be explained by redistribution of fentanyl from brain into pharmacodynamically inert tissues.

Anesthesia, Intravenous↗
PubMed1985

Evaluating a filter device used for intermittent intravenous drug delivery to newborn infants.

Injection of aminoglycosides into a filter chamber was compared with retrograde injection into i.v. tubing for delivery of intermittent drug dosages at low infusion rates in neonates. In 50 infants receiving gentamicin sulfate and 21 receiving amikacin sulfate for at least two days by retrograde i.v. infusion, peak and trough concentrations of the drugs were obtained. A subsequent dose was administered using the filter device, and peak and trough concentrations were obtained. For each infant, the difference between trough and peak concentration (delta C) was compared for the two methods. In vitro testing for gentamicin concentration was performed using the same infusion systems (10 trials for each system). For both in vivo and in vitro testing, the infusion flow rate was 10 mL/hr. For infants receiving gentamicin, delta C was greater for the filter device in 32, greater for retrograde infusion in 13, and equal in 5. The mean gentamicin delta C was significantly greater for the filter chamber method than for retrograde infusion. The in vitro studies showed significantly better gentamicin recovery with the filter device than with retrograde infusion. For amikacin, delta C was greater for the filter device in 15 infants, but the mean amikacin delta C was not significantly different for the two methods. At low flow rates commonly used in infants, the infusion system using the filter device was equal to or superior to retrograde infusion for ensuring complete delivery of intermittent drug doses.

Amikacin↗
PubMed1985

Postmortem redistribution of digoxin in rats.

Adult male Wistar rats were treated with either 0.1 or 3 mg/kg body weight X day of digoxin for five days, then killed and stored at 4 degrees C for 12 h in an attempt to mimic the normal preautopsy procedures in our hospital. In rats treated with 0.1 mg/kg body weight X day, the antemortem serum digoxin concentrations (SDC) were 1.1 +/- 0.4 ng/mL while the 12-h postmortem concentration was markedly increased (16.3 +/- 5.9 ng/mL) (P less than 0.01). In rats treated with 3 mg/kg body weight X day, SDC was not changed significantly (11.2 +/- 4.8 ng/mL antemortem and 13.3 +/- 6 ng/mL postmortem). Postmortem redistribution of digoxin was assessed by injection of 125I-labelled digoxin with or without pretreatment with the unlabelled drug. The results indicate that after death passive redistribution of digoxin may take place. When the SDC are within the therapeutic or low toxic range, digoxin may reenter the blood. High antemortem serum concentrations of digoxin may prevent such passive redistribution. Therefore, antemortem digoxin intoxication cannot be reliably inferred on the basis of high postmortem levels of the drug. Digoxin intoxication can be ruled out when postmortem SDC remain within the therapeutic range. The above changes cast doubt on some of the forensic and cardiologic literature, which has in the past been based on incorrect assumptions concerning postmortem behavior of digoxin.

Animals↗
PubMed1985

Optimization of gentamicin therapy in very low birth weight infants.

In order to optimize gentamicin (G) therapy we studied G pharmacokinetics in 48 preterm infants (gest. age 31.6 +/- 3.4, range 25-37 wk; birth weight 1.5 +/- 0.5 kg, range 0.7-2.5 kg). They received IV G twice daily (5.2 +/- 0.6 mg/kg/day). After at least 2 days of treatment trough and peak levels were measured for 2 successive doses. Trough levels were significantly higher in infants less than 1 kg receiving 5 mg/kg/day than in other infants (1-2.5 kg) who received the same dose (3.1 +/- 1.0 vs. 2.3 +/- 0.5 micrograms/ml; p less than 0.01). Mean G t 1/2 was significantly longer in infants under 1 kg than in those weighing 1-2.5 kg (7.9 +/- 1.9 and 6.5 +/- 1.6 hr, respectively; p less than 0.01). These differences could be attributed to lower G clearance in infants less than 1 kg (31 +/- 6 vs. 39 +/- 8 ml/kg/hr; p less than 0.005). There was no difference in G distribution volume between less than 1 kg and 1-2.5 kg infants (0.35 +/- 0.07 and 0.38 +/- 0.13 L/kg, respectively). A correlation was found between clearance and t 1/2 for the total group (r = 0.57, p less than 0.01). No correlation was detected between BUN and clearance or between gestational age and clearance. Our data suggest that G dose in infants less than 1 kg should be reduced to 3.5-4 mg/kg/day in order to avoid excessive levels associated with nephrotoxicity.

Birth Weight↗
PubMed1985

Complications resulting from use of arterial catheters: retrograde flow and rapid elevation in blood pressure.

Arterial catheters, routinely used in neonatal intensive care units, have been associated with serious complications. In the present studies, retrograde blood flow occurring during routine flushing of peripheral and umbilical catheters is described. This retrograde flow is associated with a significant elevation of blood pressure at distant sites. These phenomena depend on the volume flushed and on the velocity of the flushing process. These phenomena can be prevented by flushing a small volume of 0.5 mL for a period of five seconds.

Birth Weight↗
PubMed1985

The pharmacokinetics of inhaled N2O in children.

A new approach is described for the calculation of elimination half-life of inhaled N2O. We generated the elimination rate constant (Ke) by measuring the cumulative fraction of exhaled N2O versus time during induction of anaesthesia with oxygen and nitrous oxide. The amount of N2O which remained in the body at 90% steady-state (X1 90%) was estimated by subtracting the cumulative exhaled N2O from the cumulative inhaled N2O. In young children (age range 4-36 mo, mean 19 mo) the elimination rate constant was significantly higher than in adolescents and young adults (age range 14-20 yr, mean 16.8 yr) (0.14 +/- 0.055/sec and 0.0646 +/- 0.019/sec, respectively) (P = 0.025). Elimination T1/2 was therefore shorter in the young children (6.1 +/- 3.3 vs 11.1 +/- 3 sec) (P less than 0.025). T1/2 was longer (14 +/- 2.6 sec) in children with left to right shunt despite being younger than the adolescents and young adults (age range 3.25-15 yr, mean 9.9). X1 90% was significantly larger in the young children (30 +/- 3% of the administered dose) than in the older children (26.7 +/- 2%) (P less than 0.05). Elimination T1/2 positively correlated with the amount of N2O which remained in the body at 90% steady-state (X1 90%) (r = 0.85, P less than 0.01), suggesting that the distribution of N2O and not its clearance is the main determinant of its elimination T1/2 in normal children.

Adolescent↗
PubMed1985

Theophylline pharmacokinetics in adolescent females following coadministration of oral contraceptives.

The influence of 3-9 months of combined low dose oral contraceptives on theophylline pharmacokinetics was studied in 10 adolescent females (age 15-18 years, mean +/- SD 17 +/- 1) and compared to 10 age-matched control subjects (age 13.8-19 years, mean +/- SD 16.5 +/- 1.6). The distribution volume (0.44 +/- 0.06 L/kg in control vs. 0.44 +/- 0.09 L/kg oral contraceptive group), total body clearance (0.78 +/- 0.13 ml/kg/min vs 0.78 +/- 0.18 ml/kg/min) and elimination T 1/2 (402 +/- 78 min vs. 409 +/- 126 min) were identical in the two groups. It appears that during the first 3-9 months of low dose oral contraceptive treatment, these steroids do not alter the pharmacokinetic behaviour of theophylline in adolescent females.

Adolescent↗
PubMed1985

Morphine-induced seizures in newborn infants.

Two neonates suffered from generalized seizures during the course of intravenous morphine sulfate for post-operative analgesia. They received morphine in doses of 32 micrograms/kg/hr and 40 micrograms/kg/hr larger than a group of 10 neonates who received 6-24 micrograms/kg/hr and had no seizures. Plasma concentrations of morphine in these neonates was excessive (60 and 90 mg/ml). Other known reasons for seizures were ruled out and the convulsions stopped a few hours after cessation of morphine and did not reoccur in the subsequent 8 months. It is suggested that post-operative intravenous morphine should not exceed 20 micrograms/kg/ml in neonates.

Humans↗