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Biomedical subjects

J R Koup

Publications and source records attributed to J R Koup.

At least 73 records · Page 4Linked to original sources
PubMed1980

Effect of hemodialysis on total body clearance of chloramphenicol.

The effect of hemodialysis on the total body clearance (ClTB) of chloramphenicol was studied in two patients with renal failure and hepatic dysfunction. Chloramphenicol sodium succinate was administered intravenously eight hours before dialysis in doses of 20 and 26.1 mg/kg/day to Patients 1 and 2, respectively. Serum samples were taken at 48 hours after initiation of the drug, 2.5 hours after the last dose and 5 minutes into dialysis for Patient 1, and before dosing and at 0.5, 1, 2, 4, 6, 8 and 11 hours after dosing for Patient 2. Serum levels of chloramphenicol were measured by high-performance liquid chromatography. Chloramphenicol ClTB values on dialysis (162.2 and 118 ml/min for Patients 1 and 2, respectively) were 58% and 72% higher than off-dialysis ClTB values (102.9 and 69 ml/min) for Patients 1 and 2, respectively. Dialysis extraction ratios for chloramphenicol were 0.52 and 0.31 for Patients 1 and 2, respectively. Although the increased clearance of chloramphenicol that occurred during dialysis may be important only in patients with hepatic dysfunction, it is recommended that the normal maintenance dose of the drug be administered after dialysis to avoid the possibility of increased clearance.

Adult↗
PubMed1980

Chloramphenicol pharmacokinetics in infants and young children.

We measured serum chloramphenicol concentrations in 17 hospitalized pediatric patients (aged 1 month to 6 years) after intravenous infusion of chloramphenicol succinate. The serum T1/2 ranged from 2.1 to 8.3 hours with a mean of 3.98 (SD 1.75) hours, while the apparent volume of distribution ranged from 0.78 to 2.09 liters/kg with a mean of 1.39 (SD 0.34) liters/kg. The total body clearance ranged 0.122 to 0.429 liters/kg/hour with a mean of 0.281 (SD 0.117) liters/kg/hour. Two patients were restudied, and had increased clearance during their hospitalization. Because of the wide variability in pharmacokinetics, we conclude that serum chloramphenicol concentrations should be monitored in infants and children.

Child↗
PubMed1980

Factors affecting theophylline pharmacokinetics in premature infants with apnea.

Theophylline disposition was examined in 17 premature neonates (birth weight 760--1,480 g) at cessation of therapy for primary apnea Mean +/- SD of clearance (22.9 +/- 3.9 ml/h/kg) and apparent volume of distribution (0.630 +/- 0.150 1/kg) were somewhat greater than previously reported for newborn infants at 4--15 days. Better correlations were found between maturational factors and clearance adjusted for body surface area than for clearance adjusted for weight. A limited correlation (r = 0.53) was found between clearance/body surface area and duration of therapy. No significant differences in pharmacokinetics occurred in patients who received parenteral alimentation. While some variability and age dependence exists in theophylline disposition in newborns, such variability is substantially less than found in older children and in adults.

Age Factors↗
PubMed1979

Stability of pulmonary function during periodic intravenous bolus aminophylline therapy.

Peak expiratory flow, forced vital capacity, forced expiratory volume at 1 sec, and midmaximal expiratory flow were measured immediately before and 1 hr after a scheduled intravenous maintenance dose of aminophylline in 12 recently hospitalized asthmatic patients. Serum theophylline concentrations were also determined. No significant improvement was noted in any of these pulmonary function tests despite a significant increase in serum theophylline concentration (10.5 +/- 5.2 to 18.2 +/- 6.3 micrograms/ml, p < 0.001). These results were consistent with previously developed pharmacologic response theory.

Aminophylline↗
PubMed1979

Chloramphenicol pharmacokinetics in hospitalized patients.

The apparent body clearance of chloramphenicol was investigated in 21 hospitalized adult patients on 27 occasions. Apparent body clearance was found to be significantly lower (1.99 +/- 1.49 ml/min per kg) in patients with total serum bilirubin concentrations of >1.5 mg/100 ml than in patients with serum bilirubin concentrations of </=1.5 mg/100 ml (3.57 +/- 1.72 ml/min per kg; P < 0.001). Serum protein binding of chloramphenicol was lower in cirrhotic patients (42.2 +/- 6.8% bound) than in normal adults (53.1 +/- 5.2% bound; P < 0.001). Low binding of chloramphenicol was also found in the serum of premature neonates (32.4 +/- 8.2% bound; P < 0.001). Reduced binding in neonates implies the need for a lower therapeutic range of total chloramphenicol concentration (3.5 to 13.9 mug/ml) compared with the usual adult range (5 to 20 mug/ml). Finally, three case reports are presented which demonstrate marked abnormalities and intrasubject variation in chloramphenicol clearance.

Adolescent↗
PubMed1979

Relationship between serum and saliva chloramphenicol concentrations.

The relationship between serum and saliva chloramphenicol (CAP) concentrations was evaluated in 27 paired specimens collected from 20 hospitalized patients during therapy with the drug. A significant (R = 0.80, P < 0.001) but variable relationship was found to exist. Serum protein binding of CAP was also evaluated (43.7 +/- 5.7% bound; N = 24). Differences in CAP binding did not apparently account for a significant portion of the variability in the observed saliva/serum CAP concentration ratios. The degree of variation observed indicated that saliva CAP concentrations could not be relied upon for the prediction of serum CAP concentrations.

Adult↗
PubMed1979

Single point clearance estimation.

Linear relationships were observed between the log of total body clearance (C1B) and simulated serum concentrations (Cmin) six hours after a test dose of chloramphenicol, as well as between C1B and the reciprocal of Cmin. Correlation coefficients for these relationships were 0.988 and 0.977, respectively. Clearance estimates obtained from a single serum sample following a test dose of a drug may prove to be a useful method of predicting dosage requirements for individual patients.

Chloramphenicol↗
PubMed1978

Interaction of chloramphenicol with phenytoin and phenobarbital. Case report.

The effect of chloramphenicol therapy (48 mg/kg/day) on the serum concentrations of phenytoin and phenobarbital was studied in a patient previously stabilized on anticonvulsant medications. Phenytoin, 12 mg/kg/day, and phenobarbital, 5 mg/kg/day resulted in serum concentrations averaging 10.8 microgram/ml before and 30.5 microgram/ml, after chloramphenicol therapy. A reduction in dose of both phenytoin and phenobarbital was required to minimize adverse effects during the course of chloramphenicol therapy. An average daily dose of phenytoin of 9.1 mg/kg resulted in an average serum concentration of 17.8 microgram/ml. A daily dose of phenobarbital of 4.0 mg/kg resulted in an average serum concentration of 37.1 microgram/ml. These changes indicate 50.5% and 40.4% decreases in clearance of phenytoin and phenobarbital. Multiple-dose nonlinear regression analysis of phenytoin and phenobarbital serum concentration data obtained during chloramphenicol therapy indicated a 62.5% and a 29.5% decrease in clearance. Subsequent serum concentration monitoring demonstrated a similar reduction in phenobarbital clearance when chloramphenicol was added to phenobarbital alone.

Adult↗
PubMed1978

Ethosuximide pharmacokinetics in a pregnant patient and her newborn.

Ethosuximide concentration in serum was monitored during the last trimester of pregnancy in a patient. After delivery, the decline in serum concentration of ethosuximide was observed in the nonnursing neonate. The half-life of elimination of transplacentally acquired ethosuximide in this neonate was 41.3 hr. The ratio of breast milk to maternal serum concentration of ethosuximide was approximately 1. A total daily exposure to ethosuximide of 12.8 to 38.4 mg (3.6 to 11.0 mg/kg) as a result of nursing was predicted.

Adult↗
PubMed1978

High-performance liquid chromatographic assay of chloramphenicol in serum.

A new method for the analysis of serum chloramphenicol by reversed-phase, high-performance liquid chromatography (HPLC) is described. The method involves a preliminary extraction of 0.1 ml of serum with ethyl acetate containing an internal standard, chromatography with a reversed-phase C18 microparticulate column with an acetonitrile-acetate buffer mobile phase, and detection by measuring UV absorbance at 270 nm. Assay performance was compared with an existing microbiological assay. The HPLC method demonstrated both increased precision and increased sensitivity. The specificity of the HPLC method was also evaluated. The new method presents an alternative approach to the analysis of clinical specimens.

Chloramphenicol↗
PubMed1978

Comparison of homogeneous enzyme immunoassay and high-pressure liquid chromatography for the determination of theophylline concentration in serum.

A comparison of the new homogeneous enzyme-multiplied immunoassay technique (EMIT, Syva) with a high-pressure liquid chromatographic technique for the determination of theophylline concentration is presented. The accuracy, precision, and specificity of the methods were compared. In addition, 100 samples from 61 pediatric patients receiving theophylline were assayed by both methods. The accuracy, precision, and specificity of the enzyme immunoassay support the use of this method for the quantification of theophylline concentration in clinical specimens. A significant correlation (R = 0.981, P less than 0.001) was found between results generated by enzyme immunoassay and high-pressure liquid chromatography for patient samples. The regression line relating these results had an intercept of 0.22 microgram per ml, a slope of 1.05, and a standard error of the estimate of 1.36 microgram per ml.

Caffeine↗
PubMed1978

A useful method for predicting creatinine clearance in children.

A practical method for predicting creatinine clearance for pediatric patients from serum creatinine concentration and patient age is presented. Creatinine excretion rate (ER) can be predicted from the patient's age, in years, by the formula: ER = (0.035 X age) + 0.236. Using the predicted excretion rate and serum creatinine concentration, creatinine clearance can be predicted. There was good correlation (r = 0.90) between predicted and observed creatinine clearances in 101 subjects with various degrees of renal impairment. This method allows renal function to be rapidly estimated.

Adolescent↗