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Biomedical subjects

L A Bauer

Publications and source records attributed to L A Bauer.

68 records · Page 4Linked to original sources
PubMed1980

Theophylline hemodialysis clearance.

The hemodialysis clearance, total body clearance off dialysis, and protein binding for theophylline were determined in a 64-year-old cigarette-smoking male in acute renal failure. The hemodialysis clearance of 39.4 ml/kg/hr was comparable to two other reports and indicated that theophylline was significantly hemodialyzed. The total body clearance of 52.4 ml/kg/hr was similar to that observed in non-renal-failure smoking patients and suggested that renal failure did not appreciably affect the total body clearance in the patient. The plasma protein binding was 40% before dialysis and 33% after dialysis. This finding implied that renal failure and hemodialysis may alter protein binding compared to that in normal adults. Theophylline plasma levels should be monitored in renal failure patients because the drug is hemodialyzed. Decreased plasma protein binding may indicate the need for a lower therapeutic range in this patient population.

Acute Kidney Injury↗
PubMed1980

Amikacin pharmacokinetics in morbidly obese patients.

The pharmacokinetics of single-dose amikacin sulfate was studied in seven morbidly obese patients to determine the fraction of fat weight (FW) that, when added to ideal body weight (IBW), will normalize the volume of distribution. Seven patients (mean total body weight of 166.5 kg) were each given a 1,250-g intravenous injection of amikacin. Amikacin serum levels over eight hours were measured by radioimmunoassay. A correction factor (CF) of 0.38 was found to normalize the patients' volume of distribution (Varea) to 0.26 liters/kg, when added to the patients' IBW. There was no significant difference between peak amikacin levels predicted using the actual Varea and using the Varea plus the CF. Predictions using the actual Varea and those using Varea estimated by ideal body weight were significantly different. In morbidly obese patients, peak amikacin serum levels can be predicted best when a volume of distribution based on IBW plus a correction factor of 38% of FW is used.

Adult↗
PubMed1979

Tobramycin pharmacokinetics in morbidly obese patients.

Tobramycin kinetics were examined in 9 morbidly obese women following a single intravenous (120 mg) bolus. After the injection, serum elimination conformed to a 2-compartment open model with alpha and beta t1/2s of 0.285 and 2.1 hr. The volume of distribution (Varea) was determined to be 0.44 1/kg ideal body weight (IBW) and 0.20 1/kg total body weight (TBW). To normalize Varea to 0.26 1/kg, 58% of the patients' adipose weight (TBW -- IBW) must also be taken into account.

Anti-Bacterial Agents↗
PubMedDate not supplied

The pharmacokinetics of thiabendazole and its metabolites in an anephric patient undergoing hemodialysis and hemoperfusion.

The pharmacokinetics of thiabendazole and its metabolites were determined after the first dose and during hemodialysis and hemoperfusion in an anephric female patient treated for a strongyloides infection. The half-live, volume of distribution, and clearance for thiabendazole were 1.17 hour, 2.76 liters/kg, and 27.2 ml/min . kg, respectively. While thiabendazole and the 5-OH metabolite did not accumulate during multiple dosing, the glucuronide and sulfate esters accumulated extensively despite hemodialysis and hemoperfusion. Hemodialysis clearances for all compounds were poor. Hemoperfusion removal was much better but declined rapidly after the first hour. If rapid removal of thiabendazole and its metabolites is required, the hemoperfusion column should be changed hourly.

Adult↗
PubMedDate not supplied

Phenobarbital overdose: a kinetic approach.

A case that utilizes a pharmacokinetic approach to evaluate the need for withdrawal prophylaxis after a phenobarbital overdose is presented. To date, the practitioner has had to rely on an accurate drug-use history to predict which patients may be at risk for withdrawal symptoms. Since this information is often difficult to obtain, some other means of identifying potential withdrawal-syndrome patients would be useful. This case describes the successful use of kinetically determined parameters, the elimination rate constant and half-life, in predicting withdrawal potential. This easily used kinetic approach may provide practitioners with a useful tool for predicting those patients at risk for withdrawal symptoms following phenobarbital overdose.

Adult↗
PubMedDate not supplied

Influence of age on theophylline clearance in patients with chronic obstructive pulmonary disease.

Theophylline total body clearance was calculated in 59 adult patients requiring intravenous aminophylline therapy. Group 1 consisted of 36 chronic obstructive pulmonary disease patients who were cigarette smokers without other conditions known to alter theophylline kinetics (age range: 22 to 79 years). Group 2 consisted of 23 chronic obstructive pulmonary disease patients who were cigarette smokers with a similar degree of congestive heart failure, but free of other characteristics or diseases that affect theophylline disposition (age range: 41 to 81 years). When individual theophylline total body clearance values were plotted against age in each group, poor correlation coefficients were found, indicating that age is not a good predictor of total body clearance of theophylline (group 1: r = 0.101; group 2: r = 0.276). Each group was also broken into 'younger' and 'older' patients. No significant differences in theophylline total body clearance values were found between the younger and older patients for either group I or 2, suggesting that a theophylline dosage reduction is not necessary in cigarette smoking patients over an arbitrary age limit.

Adult↗
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↗
PubMedDate not supplied

Phenytoin Michaelis-Menten pharmacokinetics in Caucasian paediatric patients.

The Michaelis-Menten pharmacokinetic parameters Vmax and Km were calculated for 135 epileptic paediatric patients receiving phenytoin as their only anticonvulsant therapy. Mean Vmax and Km values were 13.95 mg/kg/day and 6.59 micrograms/ml for 0.5 to 3-year-old patients, 10.93 mg/kg/day and 6.82 micrograms/ml for the 4 to 6 year age group, 10.05 mg/kg/day and 6.51 micrograms/ml for the 7 to 9-year-olds, and 8.25 mg/kg/day and 5.69 micrograms/ml for the 10 to 16 year group. Using analysis of variance, the Vmax values were significantly different (p less than 0.01) but the Km values were not. Linear regression analysis of Vmax versus age revealed a significant decline in Vmax with age (r = -0.554; p less than 0.001). A plot of Km versus age showed a poor correlation (r = -0.170) and a large amount of variability. Based on this data, the youngest age group would require on average 62% more phenytoin/kg/day than the oldest age group in order to maintain a steady-state phenytoin concentration of 15 micrograms/ml. Because of these age-related pharmacokinetic differences, phenytoin dosages may require adjustment as paediatric patients become older.

Adolescent↗
PubMedDate not supplied

Influence of pharmacokinetic diurnal variation on bioavailability estimates.

The effects of diurnal variation on bioavailability assessments were examined using computer-simulated data based on the changes observed in theophylline kinetics. During one 12-hour dosage interval (noon to midnight), clearance was assumed to be larger than during the other dosage interval (midnight to noon). Oral data was simulated until steady-state occurred. Intravenous bolus data, which represented a stable-isotope pulse dose, was also simulated for both the high and low clearance dosage intervals. When the respective areas under the serum concentration-time curves were compared, the systemic availability (F = AUCpo/AUCiv) during the dosage interval with the larger clearance was greater than 1.0, but during the dosage interval with the smaller clearance it was less than 1.0. When computing the bioavailability of a drug, diurnal variations should be assessed as a potential cause of variation.

Biological Availability↗
PubMedDate not supplied

Nonlinear regression program to individualize oral theophylline dosage.

Theophylline pharmacokinetic values were estimated by two similar computer-assisted methods, and the predictive ability of these methods was evaluated. In each of two study phases, baseline serum theophylline concentrations were obtained in 20 adults receiving oral theophylline for chronic obstructive pulmonary disease; the subjects received no theophylline for 48 hours before start of each phase. In phase 1 all patients received theophylline 400 mg followed by 300 mg every six hours for three doses, and serum theophylline concentrations were measured at 0-6 hours and at 24 hours. In phase 2 patients received individualized theophylline doses calculated from phase 1 data. Predictive method 1 used measured serum theophylline concentrations at 2, 6, and 24 hours to estimate pharmacokinetic values, and method 2 used concentrations at 6 and 24 hours. The computer-predicted values were used to calculate 24-hour serum theophylline concentrations for individualized regimens in phase 2; these were compared with the measured concentration. Pharmacokinetic values predicted by both methods were compared with values based on data obtained after the loading dose in phase 1. Both methods were unbiased when predicting clearance, half-life, and volume of distribution. Estimates of half-life and volume of distribution were significantly more precise with method 1. Both methods underpredicted serum theophylline concentration at 24 hours. The greater number of serum concentrations in method 1 allowed more precise prediction of t1/2 and V; in instances where precision is not critical, method 2 is an acceptable alternative.

Adult↗
PubMedDate not supplied

Gentamicin and tobramycin pharmacokinetics in patients with cystic fibrosis.

Pharmacokinetic variables were compared in patients with cystic fibrosis receiving gentamicin or tobramycin for the treatment of a pseudomonas pulmonary infection. Sixty-nine pediatric patients receiving gentamicin sulfate (n = 31) or tobramycin sulfate (n = 38) were studied. Doses were administered every six hours. All patients received concurrent ticarcillin therapy, had a mild fever, and normal hematocrit and serum creatinine values. Amino-glycoside pharmacokinetic variables were calculated. Tobramycin and gentamicin serum concentrations were determined by radioimmunoassay. The mean (+/- S.D.) half-lives for the tobramycin and gentamicin patients were 1.2 +/- 0.5 and 1.4 +/- 0.4 hr, respectively. The average volume of distribution and clearance values for the tobramycin and gentamicin patients were 0.33 +/- 0.20 liters/kg and 2.98 +/- 0.80 ml/min/kg, and 0.35 +/- 0.15 liters/kg and 2.79 +/- 0.75 ml/min/kg, respectively. There were no significant differences between the kinetic variables in the patients receiving gentamicin or tobramycin. To achieve steady-state peak concentrations between 7 and 9 micrograms/ml and trough concentrations below 2 micrograms/ml, gentamicin patients required 10.3 +/- 3.2 mg/kg/day and tobramycin patients required 11.1 +/- 3.9 mg/kg/day. Because of the large amount of interpatient variability in maintenance dosage requirements, therapy should be initiated with 2.5 mg/kg of gentamicin or tobramycin given every six hours and then individualized on the basis of serum concentrations and clinical response.

Adolescent↗