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Biomedical subjects

L A Bauer

Publications and source records attributed to L A Bauer.

At least 37 records · Page 2Linked to original sources
PubMed1989

Influence of nifedipine therapy on indocyanine green and oral propranolol pharmacokinetics.

Nine healthy adults were administered indocyanine green (ICG) 0.5 mg.kg-1 IV alone and after the administration of the following oral drugs: nifedipine 10 mg, propranolol 80 mg, propranolol 80 mg and nifedipine 10 mg, and propranolol 80 mg after nifedipine 10 mg every 8 h for 5 days. Heart rate and mean arterial blood pressure (MAP) were also determined. Nifedipine increased ICG clearance by 14% and decreased t1/2 by 26%. Propranolol decreased ICG clearance by 21% and increased t1/2 42%. Nifedipine and propranolol given together increased ICG clearance 63% and decreased t1/2 by 19%. All changes were statistically significant. Propranolol given after multiple doses of nifedipine did not change ICG kinetic parameters. Propranolol Cmax, tmax, oral clearance, and t1/2 did not change after nifedipine therapy. However, partial propranolol AUC values between 0-0.33, 0-0.5, 0-1.0 and 0-1.5 h were significantly larger after single and multiple doses of nifedipine indicating higher propranolol concentrations during the absorption phase. Heart rate and MAP did not change after nifedipine treatment. Similar declines in heart rate and MAP occurred after propranolol alone and propranolol after single and multiple doses of nifedipine.

Administration, Oral↗
PubMed1989

Influence of age, renal function and heart failure on procainamide clearance and n-acetylprocainamide serum concentrations.

Twenty Caucasian adult patients with ventricular tachycardia were treated with intravenous procainamide. Seven patients also had moderate congestive heart failure. Steady-state procainamide (PA) and n-acetylprocainamide (NAPA) concentrations were used to compute procainamide clearance and NAPA/PA concentration ratio. Using stepwise multiple linear regression age, creatinine clearance and congestive heart failure were found to influence procainamide clearance significantly (p less than 0.05). Age and creatinine clearance effected the NAPA/PA concentration ratio (p less than 0.05). Based on this data, age appears to have an independent effect on both procainamide clearance and the NAPA/PA ratio that is separate from the decline in renal function that occurs in elderly patients.

Acecainide↗
PubMed1988

Glipizide pharmacokinetics in young and elderly volunteers.

The effects of aging on the pharmacokinetics of glipizide were studied. Ten healthy young men (24.9 +/- 1.9 years of age) and 10 healthy older men (74.4 +/- 7.9 years of age) each ingested a single 5-mg tablet of glipizide after an overnight fast. Blood samples were obtained immediately before drug ingestion and at 10, 20, 30, 45, 60, 90, and 120 minutes and at 3, 4, 6, 8, 10, 12, and 24 hours after drug ingestion. Serum samples were assayed for glipizide content by a modified high-pressure liquid chromatographic method. Clearance, volume of distribution at steady state, and half-life were estimated from the serum concentration-time curve data. Area under the concentration-time curve and area under the moments curve were calculated using the trapezoidal rule. The mean values for young and older subjects for time to peak concentration (2.1 versus 2.5 hours), peak concentrations (465 versus 399 micrograms/mL), elimination half-life (4.2 versus 4.0 hours), clearance (38.8 versus 38.1 mL/min), and distribution volume at steady state (12.5 versus 14.3 L) were not significant. However, two older individuals had a markedly prolonged time to peak concentration (six to eight hours). For 8 of the 20 subjects a more prolonged terminal half-life may have existed. Further study is required to determine whether significant pharmacokinetic differences between young and elderly subjects appear with multiple dosing of glipizide.

Adult↗
PubMed1987

Systemic absorption of endotracheally administered aminoglycosides in seriously ill patients with pneumonia.

A study was performed with 10 hospitalized patients to determine the percentage of an aminoglycoside dose (tobramycin or gentamicin) that is absorbed systemically after being instilled into the endotracheal tube at steady state. All patients were on respirators, had indwelling urinary catheters, and had creatinine clearances estimated to be greater than or equal to 40 ml/min. Tobramycin or gentamicin (40 mg) was instilled every 4 h directly into the endotracheal tube. Nine patients also received systemically a different aminoglycoside from that administered through the endotracheal tube. Urine was collected over a 4-h dosing interval at steady state (after at least 5 doses of the drug). The amount of aminoglycoside excreted over the 4-h interval was measured and expressed as percentage of the dose administered over that period. The range of percentage of dose absorbed was 1.5 to 34%, with a mean of 16.7 +/- 11.4% standard deviation and a median of 16.5%. The coefficient of variation was 68%. Levels of the endotracheally administered aminoglycoside in serum were measured, and all were less than 1.0 microgram/ml. While a large degree of variability in absorption was observed in this study, significant amounts of aminoglycosides could be absorbed in some patients. However, levels apparently did not accumulate in sera of patients with adequate renal function, and an empirical dosage reduction in intravenous aminoglycoside should not be necessary with the addition of endotracheally instilled aminoglycoside in patients with creatinine clearances greater than 40 ml/min.

Absorption↗
PubMed1986

Changes in antipyrine and indocyanine green kinetics during nifedipine, verapamil, and diltiazem therapy.

Ten healthy subjects received oral antipyrine and intravenous indocyanine green (ICG) alone and after 5 days of oral nifedipine, diltiazem, and verapamil. Antipyrine clearance decreased during verapamil (range 4% to 26%) and diltiazem (6% to 24%) therapy (P less than 0.001) but did not change during nifedipine treatment. Antipyrine t1/2 also increased during verapamil and diltiazem treatment (P less than 0.001). ICG clearance did not change during diltiazem therapy but increased during dosing with nifedipine and verapamil (P less than 0.05). Estimated liver blood flow (derived from ICG clearance and hematocrit) also increased during verapamil (mean 33%) and nifedipine (mean 27%) treatment (P less than 0.05). Drug interactions with other liver-metabolized drugs may occur during therapy with these calcium antagonists. Nifedipine appears to increase liver blood flow whereas diltiazem inhibits oxidative drug metabolism. Drug interactions with verapamil could involve both mechanisms.

Adult↗
PubMed1986

Phenytoin removal by plasmapheresis in renal insufficiency.

The removal of phenytoin by plasmapheresis in a patient with compromised renal function is described. The results indicate that plasma concentrations of total phenytoin increase after plasmapheresis, while unbound phenytoin plasma concentrations and free fraction decrease. The amount of phenytoin removed was 36 mg and, when expressed as a fraction of total body stores, equaled 2.8%. The negligible amount of total body phenytoin removed during plasmapheresis was the result of an increased volume of distribution due to renal failure and hypoalbuminemia. Our results indicate that the removal of phenytoin by plasmapheresis is likely to be greatest when its free fraction is the lowest and blood flow the highest. The data suggest that replacement of phenytoin after plasma exchange may be unnecessary but in all cases should be based on unbound concentrations or the determination of the absolute amount of phenytoin removed during the procedure.

Adult↗
PubMed1986

Impact of an aminoglycoside kinetic service on aminoglycoside use in a community hospital.

The effectiveness of an aminoglycoside monitoring service in improving the prescribing patterns of physicians in the hospital was evaluated. A drug utilization review (DUR) done as part of routine monitoring demonstrated a deficiency in eight of 19 elements based on national DUR standards. An aminoglycoside monitoring program developed by the Pharmacy Department was then implemented. A comparative DUR demonstrated significant improvement in five previously deficient elements, a trend towards improvement in two elements, and no change in one element. We conclude that a concurrent drug monitoring program with aggressive pharmacy participation improves prescribing patterns by physicians.

Aminoglycosides↗
PubMed1985

Valproic acid clearance: unbound fraction and diurnal variation in young and elderly adults.

Six young (22 to 25 years old) and six elderly (60 to 88 years old) healthy adults took valproic acid, 250 mg by mouth, at 8 am and 8 pm for 5 days. On the fifth day, blood samples were drawn over each dosage interval. Both young and elderly subjects exhibited diurnal variability. Total and unbound clearances in the young and elderly subjects were about 10% and 15% higher during the evening. These changes led to lower total and unbound steady-state and peak concentrations during the nighttime dosage interval. There were no differences in total steady-state concentrations and kinetics computed from total concentrations between the young and elderly, but there were differences in unbound steady-state concentrations and kinetics. Unbound clearances were 65% lower, which resulted in unbound steady-state concentrations 67% higher in the elderly. The average unbound fractions in the elderly and young were 10.7% and 6.4%. To minimize the influence of diurnal variability, drug concentrations should be determined at the same time each day. Total valproic acid concentration data may be less useful in elderly patients; unbound concentrations may be more reliable in this population.

Adult↗
PubMed1985

Cimetidine clearance in the obese.

Six subjects with normal weight (mean weight = 62 kg) and six obese subjects (mean weight = 140 kg) were given a single intravenous cimetidine infusion of 600 mg over 10 to 15 minutes. Both groups of subjects had normal serum creatinine levels and were matched with respect to age, desirable body weight, height, renal function, and sex. Compared with subjects of normal weight, obese subjects had higher cimetidine systemic (1147 and 637 ml/min) and renal (808 and 318 ml/min) clearances. Volume of distribution at steady state was of the same order for the two groups (82 and 84 L), but the t 1/2 was shorter in the obese group (1.2 and 1.9 hr). Obese subjects had lower cimetidine sulfoxide serum concentrations and greater cimetidine sulfoxide renal clearance (856 and 509 ml/min). Cimetidine systemic clearance and cimetidine sulfoxide renal clearance values were of the same order in the two groups when normalized by the value of weight raised to the 0.76 and 0.5 powers. Under the assumptions of an average weight of 70 kg and that average serum concentrations produced by cimetidine, 300 mg iv every 6 hours, are appropriate, people with normal renal function and body weight usually receive 48 mg/day/weight0.76. This same dosage in obese individuals with normal serum creatinine values should result in the same average steady-state serum concentrations. In our obese subjects, the mean cimetidine dose would have been approximately 500 mg iv every 6 hours.

Adult↗
PubMed1985

Influence of high-dose pentobarbital on theophylline pharmacokinetics: a case report.

The effect of high dose pentobarbital coma therapy on the total body clearance of theophylline (CLT) was evaluated in a neurosurgical patient. Preinduction and induction CLT were 4.22 and 8.02 L/h, respectively, which represented a 95% increase in the CLT as a consequence of pentobarbital therapy. Although barbiturates have been shown to induce hepatic microsomal enzymes, previous reports minimize their effect on CLT in humans. This case report demonstrates remarkable alterations in the CLT as a result of high doses of pentobarbital, necessitating the need for substantial dosage adjustments of theophylline.

Aminophylline↗
PubMed1984

Diurnal variation in valproic acid clearance.

Diurnal variation in total and unbound valproic acid concentrations was measured at steady state in seven healthy men and three healthy women after 250-mg oral doses every 12 hr. Total average steady-state concentration (Css) during the morning dosage interval was 50.4 mg/l. During the evening dosage interval, total Css was 45.7 mg/l. Unbound Css was also less during the evening (2.9 and 3.4 mg/l). These changes were due to higher total and unbound clearance rates during the evening dosage interval. Total peak concentrations were lower (56.8 and 64.3 mg/l) and time of peak concentrations slightly longer (2.2 and 1.8 hr) during the evening. There was marked interindividual variability in all these changes. For best reproducibility of steady-state valproic acid concentrations, our results suggest that total and unbound levels be drawn at the same time of day.

Administration, Oral↗