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Biomedical subjects

L A Bauer

Publications and source records attributed to L A Bauer.

At least 55 records · Page 3Linked to original sources
PubMed1983

Influence of age on amikacin pharmacokinetics in patients without renal disease. Comparison with gentamicin and tobramycin.

The influence of age on amikacin pharmacokinetics was examined in 87 patients with normal renal function. All patients had a gram negative infection, were febrile, weighed within 20% of their ideal body weight, did not receive penicillin antibiotics concurrently, had normal hematocrits and had a measured 24 h creatinine clearance greater than 80 ml/min/1.73 m2. 31 patients were 20-39 years old, 27 patients were between the ages of 40-59 years, and 29 patients were 60-79 years old. These patients were compared to patients in similar previous studies who received gentamicin or tobramycin. No significant differences in clearance, volume of distribution or half-life were found due to age within a single drug group (amikacin, gentamicin, or tobramycin) or among the 3 drug groups. However, a substantial amount of intersubject variability existed in the calculated pharmacokinetic parameters. Patients over 40 years old tended to be underdosed with amikacin and the other 2 aminoglycosides. The average amikacin dose needed to achieve the desired steady-state concentrations was 18.9 mg/kg/day. 52% of the amikacin patients required doses greater than the recommended maximum (15 mg/kg/day). Since aminoglycoside pharmacokinetics do not change as age increases, doses do not need to be arbitrarily changed in older patients with normal renal function.

Adult↗
PubMed1983

Influence of weight on aminoglycoside pharmacokinetics in normal weight and morbidly obese patients.

Aminoglycoside pharmacokinetics were determined in 30 normal weight patients and 30 morbidly obese patients (greater than 90% overweight). All had normal renal function and a gram-negative infection (documented by cultures, fever and elevated white blood cell counts) which was treated only with aminoglycoside antibiotics. The normal weight and morbidly obese patients were matched with respect to the following criterion: age, sex, ideal body weight (IBW), serum creatinine, site of infection, and type of aminoglycoside antibiotic (gentamicin, tobramycin, or amikacin). The results were similar for all 3 drugs. Average half-life was 2 h for both the morbidly obese and normal weight patients. The mean volumes of distribution and clearances were significantly larger in the morbidly obese (23.3 l and 135.8 ml/min for gentamicin, 29.9 l and 162.4 ml/min for tobramycin, and 26.8 l and 157.3 ml/min for amikacin) than in normal weight patients (17.0 l and 95.9 ml/min for gentamicin, 18.3 l and 101.3 ml/min for tobramycin, and 18.6 l and 99.2 ml/min for amikacin). As a result of altered aminoglycoside pharmacokinetics, morbidly obese patients required significantly larger mean doses (540 mg/d for gentamicin, 690 mg/d for tobramycin and 1970 mg/d for amikacin) when compared to the normal weight patients (380 mg/d, 420 mg/d and 1420 mg/d, respectively; p less than 0.005) in order to achieve comparable serum concentrations.

Aminoglycosides↗
PubMed1983

Importance of unbound phenytoin serum levels in head trauma patients.

Total (bound + unbound) and unbound phenytoin serum concentrations were measured in ten male comatose head trauma patients and ten male epileptic patients. Serum biochemistry and complete blood cell counts were normal for both groups, except albumin concentrations were below normal in the head trauma patients for nutritional reasons. Total phenytoin concentrations were 6.8 +/- 1.8 mcg/ml for the head trauma patients and 14.5 +/- 3.0 mcg/ml for the epileptic patients (p less than 0.0002) even though phenytoin doses were similar. However, unbound phenytoin concentrations were within the therapeutic range of 1 to 2 mcg/ml for both groups and were not significantly different. Had only the total concentrations been measured, phenytoin doses might have been increased inappropriately in the head trauma patients. The reason head trauma patients had therapeutic unbound concentrations despite lower total concentrations was that the unbound per cent of phenytoin was higher in these patients (21 +/- 3.2%) than in the epileptic patients (10 +/- 1.3%, p less than 0.0002).

Adult↗
PubMed1983

Primer on clinical pharmacokinetics.

Basic concepts of clinical pharmacokinetics and principles of therapeutic drug monitoring are discussed. Pharmacokinetic variables such as volume of distribution, clearance, and half-life describe drug disposition in the body; in individual patients, these values may vary substantially. Serum concentrations of drugs may be influenced by numerous factors, such as route of administration, bioavailability, tissue distribution, and clearance. Therapeutic drug monitoring is designed to individualize drug dosages to achieve steady-state concentrations within a range of values that correlates well with patient response. An understanding of clinical pharmacokinetics and drug monitoring facilitates interpretation of serum concentrations in individual patients.

Biological Availability↗
PubMed1982

Determination of thiabendazole and 5-hydroxythiabendazole in human serum by fluorescence-detected high-performance liquid chromatography.

We have developed a rapid, sensitive and precise high-performance liquid chromatographic method using fluorescence detection for the simultaneous determination of thiabendazole and unconjugated 5-hydroxythiabendazole in serum. Sample pretreatment consists only of protein precipitation with acetonitrile containing the internal standard, 2-methylindole. Detection limits were found to be 0.1 microgram/ml serum for thiabendazole and 0.4 microgram/ml serum for 5-hydroxythiabendazole. Between-day analytical precision coefficients of variation for serum-based controls were 7% and 11% for thiabendazole levels of 1 and 5 micrograms/ml, respectively; and 43% and 8% for 5-hydroxythiabendazole levels of 6 and 60 micrograms/ml, respectively. We also devised a microenzymatic method for the conversion of the glucuronide and sulfate esters of 5-hydroxythiabendazole using beta-glucuronidase [EC 3.2.1.31] and sulfatase [EC 3.1.6.1]. Thus, quantitation of the separate metabolites was possible. We also utilized a special adaptation of the chromatographic procedure for the determination of the 5-hydroxythiabendazole metabolites in the sera of uremic patients, which can contain large amounts of interfering fluorescent substances. The method should be particularly useful for monitoring thiabendazole therapy in patients unable to eliminate the potentially toxic metabolites.

Chromatography, High Pressure Liquid↗
PubMed1982

The effect of acute and chronic renal failure on theophylline clearance.

Theophylline total body clearance was measured in 29 anuric, chronic obstructive pulmonary disease patients with acute or chronic renal failure during a continuous intravenous infusion. They were divided into two groups depending on the absence (group 1, N = 16) or presence (group 2, N = 13) of congestive heart failure and compared to normal renal function control patients with similar disease states. All study and control patients smoked cigarettes. The theophylline mean total body clearance values (+/- S.D.) for group 1 were 68.0 +/- 14.5, 64.5 +/- 12.9, and 62.6 +/- 17.3 ml/kg.hr for acute renal failure patients, uremic chronic renal failure patients, and control patients, respectively. For group 2, the corresponding values were 25.6 +/- 5.1, 28.6 +/- 8.7, and 27.4 +/- 12.9 ml/kg.hr. There was no significant difference between study and control patients in either group 1 or group 2 (P greater than 0.05, one-way analysis of variance). Since total body clearance determines the steady-state concentration of a drug after repeated administration, theophylline doses do not need to be reduced in acute renal failure or uremia patients.

Acute Kidney Injury↗
PubMed1982

Ethosuximide kinetics: possible interaction with valproic acid.

Ethosuximide kinetics were determined in six normal healthy adults after a single dose (phase 1) and at steady-state (phase 2). After the completion of phase 2, valproic acid was added to the ethosuximide regimen (phase 3) to assess the possibility of drug interaction. Between phases 1 and 2 total clearance fell from 13.1 to 11.1 ml/hr/kg (P less than 0.05) and nonrenal clearance fell from 10.1 to 8.3 ml/hr/kg (P less than 0.05). When valproic acid was added (phase 3) there was no further change in total or nonrenal clearance (11.2 and 8.3 ml/hr/kg). To assess the possibility of nonlinear ethosuximide kinetics a review was conducted of patients who received ethosuximide as sole therapy for absence seizures. Of 106 patients, 10 met the required criterion that defined steady state. Data from seven of the 10 patients showed evidence of a nonlinear relationship when steady-state ethosuximide concentrations were plotted against dose.

Adult↗
PubMed1982

Age and phenytoin kinetics in adult epileptics.

Michaelis-Menten parameters for rate of drug metabolism (Vmax) and serum concentration at which metabolism is half of Vmax (Km) were determined in 92 adult epileptic patients taking phenytoin who were 21 to 78 yr old. The patients received no known inhibitors or inducers of phenytoin metabolism. Results of physical examinations and tests of liver function and total bilirubin and albumin concentration were normal. Divided into age groups, Vmax values were 7.5 +/- 2.2, 6.6 +/- 1.8, and 6.0 +/- 1.9 mg/kg/day for the 20- to 39-, 40- to 59-, and 60- to 79-yr-old subjects, respectively. Values for those in the 60- to 79-yr-old group were substantially less than those for the youngest subjects (20- to 39-yr-olds; P less than 0.05). Linear regression analysis indicated a decline in Vmax with age (r = 0.518). Km values did not appear to be influenced by age; means ranged from 5.4 to 5.8 microgram/ml. As a result of these changes, the 60- to 79-yr-old group would require, on the average, 21% less phenytoin per day than the 20- to 39-year-olds to maintain a steady-state concentration of 15 microgram/ml. First doses can be based on these data and maintenance doses arrived at based on clinical response.

Adult↗
PubMed1982

Influence of long-term infusions on lidocaine kinetics.

Lidocaine kinetics were examined during continuous infusions in five healthy subjects using stable isotope lidocaine labeled with two deuterium atoms. During phase 1, lidocaine and stable isotope lidocaine (50 mg IV each) were given as a bolus to confirm that the two species were kinetically identical. Phase 2 consisted of a long-term (30 hr) lidocaine infusion designed to produce a steady-state concentration equal to 1.5 microgram/ml. Twenty-four hours into the infusion, stable isotope lidocaine (50 mg) was given as an intravenous bolus and kinetic parameters were calculated. Phase 3 differed from phase 2 in that target steady-state lidocaine concentration was 4 microgram/ml and the stable isotope lidocaine dose was reduced to 40 mg. A gas chromatograph-mass spectrometer was used to determine lidocaine and stable isotope lidocaine serum concentrations. Compared to phase 1, clearance decreased (P less than 0.05) and half-life increased (P less than 0.025) during phases 2 and 3. The volume of distribution at steady-state remained constant during all three phases. Lidocaine cumulated in serum during long-term infusions in all five patients; repeated decreases in infusion rate were necessary to avoid exceeding desired target concentrations in phases 2 and 3.

Adult↗
PubMed1982

Rebound gentamicin levels after hemodialysis.

After observing the phenomenon clinically, seven post-hemodialysis patients were studied for a rebound effect of gentamicin levels. Serum gentamicin levels were obtained immediately after dialysis and 1 hr postdialysis. An average 25.7% rebound occurred in the serum levels. A slow redistribution of gentamicin out of tissue into the serum is the probable mechanism. This data suggests that a short time period should be allowed before postdialysis levels are obtained to determine gentamicin replacement doses.

Acute Kidney Injury↗
PubMed1982

Gentamicin pharmacokinetics: effect of aging in patients with normal renal function.

The effects of aging on gentamicin total-body clearance, volume of distribution, and half-life were examined in 173 febrile patients with gram-negative infections. All had normal renal function, normal hematocrit levels, near-ideal body weights, and were not receiving concurrent penicillin therapy. In the 51 patients who were 20-39 years old, the mean clearance of gentamicin was 1.29 ml/min/kg, the volume of distribution was 0.23 l/kg, and the half-life was 2.2 hours. In the 59 patients 40-59 years old, these values were 1.35 ml/min/kg, 0.27 l/kg, and 2.1 hours; in the 63 patients 60-79 years old, they were 1.31 ml/min/kg, 0.26, and 2.4 hours. No significant difference was observed for any of the measures among the three age groups (P less than 0.05, analysis of variance). Linear regression revealed poor correlations between the individual measures and age. Since there is no change in gentamicin pharmacokinetics with aging, dosages do not need to be changed arbitrarily for older patients who have normal renal function.

Adult↗
PubMed1982

Vancomycin pharmacokinetics in normal and morbidly obese subjects.

In an uncontrolled study, vancomycin pharmacokinetics were determined in four normal (total body weight [TBW], 65.9 to 89.1 kg) and six morbidly obese (TBW, 111.4 to 226.4 kg) subjects. The morbidly obese subjects were investigated 3 to 4 h after gastric bypass surgery. Mean terminal half-lives, volumes of distribution, and total body clearances for the normal controls and the morbidly obese (TBW, 111.4 to 226.4 kg) subjects. The morbidly obese subjects were investigated 3 to 4 h after gastric bypass surgery. Mean terminal half-lives, volumes of distribution, and total body clearances for the normal controls and the morbidly obese subjects were 4.8 h, 0.39 liter/kg, and 1.085 ml/min per kg versus 3.2 h, 0.26 liter/kg TBW, and 1.112 ml/min per kg TBW. The mean terminal half-life and volume of distribution values were significantly different between the two groups. Strong correlations were found between TBW and both volume of distribution (correlation coefficient, 0.943) and total body clearance (correlation coefficient, 0.981). There results implied that TBW should be used to calculate vancomycin doses for morbidly obese patients. This was supported by the finding that there was no significant difference in the daily dose (in milligrams per kilogram per day) required to produce an average steady-state concentration of 15 micrograms/ml in the two groups (23.4 +/- 1.5 mg/kg per day for normal weight subjects and 24.0 +/- 3.4 mg/kg per day TBW for the postsurgery morbidly obese subjects). Therefore, the morbidly obese required higher total doses (in milligrams per day) than did normal weight subjects to achieve the same mean steady-state concentrations. In addition, normal weight and morbidly obese subjects had similar volumes of the central compartment (7.7 and 6.4 liters, respectively). To avoid high transient peak concentrations which would occur when obese patients are given larger total doses (in milligrams per day), maintenance doses may be given at more frequent intervals. The shorter mean terminal half-lives observed in morbidly obese patients allows more frequent dosing without excessive accumulation.

Adult↗
PubMed1982

Interference of oral phenytoin absorption by continuous nasogastric feedings.

Inhibition of phenytoin absorption by continuous nasogastric tube feeding was studied in 20 neurosurgery patients and 5 normal subjects. Ten patients receiving phenytoin suspension 300 mg per day coadministered with continuous nasogastric feedings had a mean phenytoin serum concentration of 2.59 micrograms per milliliter. When the feedings were discontinued, the average concentration rose to 10.22 micrograms per milliliter in 7 days. In 10 other patients stabilized on phenytoin suspension 300 mg per day, the average serum concentration decreased from 9.80 microgram per milliliter to 2.72 microgram per milliliter in 7 days when continuous tube feedings were started. Five normal subjects received a single oral dose of phenytoin suspension alone and while drinking a nasogastric tube feeding preparation orally at a rate of 100 ml per hour; phenytoin serum levels decreased an average of 71.6% when the tube feeding was taken concurrently.

Adult↗
PubMed1982

Integrated calculator programs for pharmacokinetic calculations.

A package of integrated programs for calculating pharmacokinetic variables and drug-dosing regimens using a hand-held programmable calculator is described. Twelve pharmacokinetic programs, which were based on previously published pharmacokinetic equations, were developed for use in a HP-41C hand-held calculator (Hewlett-Packard). The programs perform, pharmacokinetic calculations for many drugs, including digoxin, theophylline, phenytoin, nd the aminoglycosides. Also programs for ideal body weight, body surface area, and creatinine clearance calculations are included. Eleven of the 12 programs can be stored in the calculator at any time. Values generated in one program are stored in memory registers and can be recalled directly for use in other programs. The calculator has a continuous memory; therefore, all stored data, programs, and functions are maintained when the calculator is turned off. The integrated calculator programs provide a quick and reliable means of applying pharmacokinetic principles to everyday hospital pharmacy practice.

Computers↗
PubMed1981

Influence of age on tobramycin pharmacokinetics in patients with normal renal function.

The influence of age on tobramycin half-life, volume of distribution, and clearance was examined in 77 patients with infections due to gram-negative bacteria. All patients had normal renal function and hematocrits, were within 20% of their ideal body weight, did not receive penicillin antibiotics concurrently, and had a fever. Twenty-five patients were between 20 and 39 years of age, 23 patients were 40 to 59 years old, and 29 patients were in the age group 60 to 79 years. The mean half-lives were 2.3, 2.2, and 2.4 h, respectively, for the three age groupings. The average clearance and volume of distribution terms were, respectively, 1.34 ml/min per kg and 0.25 liter/kg for the younger group, 1.44 ml/min per kg and 0.26 liter/kg for the middle age group, and 1.25 ml/min per kg and 0.25 liter/kg for the older group. There was no significant difference among the three groups for any of the parameters (P less than 0.05, analysis of variance). Correlation coefficients determined from individual plots of the three pharmacokinetic parameters versus age revealed no correlation between any parameter and age. Forty-five percent of the patients required doses greater than the recommended maximum (5 mg/kg per day) to achieve desired steady-state concentrations. Since tobramycin pharmacokinetics do not change as age increased, doses do not need to be arbitrarily changed in older patients with normal renal function.

Adult↗
PubMed1981

Estimating creatinine clearance in morbidity obese patients.

Estimates of creatinine clearance (Clcr), using five methods, were compared to measured Clcr in morbidity obese patients. Patients whose total body weight (TBW) was greater than or equal to 195% of their ideal body weight (IBW) and who had urinary Clcr measured with 24-hour urine collections were studied. The 12 men weighed an average of 180 kg; the 31 women averaged 138 kg. The methods studied considered a combination of the following factors: weight, age, sex, and serum creatinine. One method was a nomogram; TBW could not be used because of limitations of the nomogram. Both TBW and IBW were used in two methods that considered weight as a variable. Measured Clcr averaged 105.7 ml/min/1.73 sq m body surface area. All estimating methods using IBW significantly underestimated Clcr; all methods using TBW significantly overestimated Clcr. Two methods that did not include body weight as a variable predicted Clcr more accurately than did other methods, but there was still a significant difference between estimated and measured Clcr. None of the Clcr estimation methods is accurate in morbidly obese patients.

Adult↗
PubMed1980

Theophylline clearance: effect of marked obesity.

Total body clearance (ClT) of theophylline was examined in 12 markedly obese patients and related to total body weight (TBW) and ideal body weight (IBW). Patients were infused with aminophylline continuously and evaluated at steady state. Total body clearances of theophylline were 29.5 +/- 7.8 ml/hr/kg TBW and 58.8 +/- 15.9 ml/hr/kg IBW. In patients with congestive heart failure (CHF) (N = 4) theophylline ClT was 19.7 +/- 1.9 ml/hr/kg TBW or 47.7 +/- 8.3 ml/hr/kg IBW while in those with no CHF (N = 8) clearance was 34.5 +/- 3.5 ml/hr/kg TBW or 64.3 +/- 16.2 ml/hr/kg IBW. Acute renal failure did not appear to alter theophylline ClT in two patients (one with and one without CHF). Mean theophylline ClT closely approximated that of a normal population when corrected for IBW, but there was a much stronger correlation between theophylline ClT and weight when corrected for TBW. Our data suggest that maintenance doses of theophylline in markedly obese patients with CHF should be based on a theophylline ClT of 19.7 ml/hr/kg TBW and of 34.5 ml/hr/kg TBW in those with no CHF.

Adult↗