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Biomedical subjects

L A Bauer

Publications and source records attributed to L A Bauer.

At least 19 recordsLinked to original sources
PubMed1992

Verapamil inhibits ethanol elimination and prolongs the perception of intoxication.

Ten young healthy men received verapamil (80 mg every 8 hours for 6 days) or placebo in a blinded, randomized, crossover design. On the sixth day, ethanol was administered as a single oral dose (0.8 gm/kg), and blood samples were collected over the following 12 hours for determination of verapamil, norverapamil, and ethanol concentrations. Compared with placebo, verapamil increased the peak blood ethanol concentration (106.45 +/- 21.40 to 124.24 +/- 24.74 mg/dl, p less than 0.05) and area under the ethanol concentration versus time curve (365.67 +/- 93.52 to 475.07 +/- 97.24 mg.hr/dl, p less than 0.005). Verapamil areas under the concentration versus time curves (AUC) were positively correlated (r = 0.71, p less than 0.05) to increased ethanol blood AUC values. Each subject's perception of ethanol intoxication was measured by use of a simple visual analog scale. Compared with placebo, verapamil significantly increased area under the effect versus time curve (10.19 +/- 7.6 to 13.83 +/- 7.81 cm.hr, p less than 0.002) but did not change the peak effect or time to peak effect. Ethanol effect versus concentration plots were not significantly different between verapamil and placebo treatment phases when increased ethanol concentrations during verapamil therapy were taken into account. The findings of our study suggest that verapamil significantly inhibits ethanol elimination, resulting in elevated blood ethanol concentrations that prolong the intoxicating effects of alcohol.

Adult↗
PubMed1992

Accuracy of duplex scanning for measurement of arterial volume flow.

This study examined the accuracy of duplex ultrasound measurements of volume flow in a baboon model. Volume flow (Vf) through the external iliac artery was calculated from measurements of blood velocity averaged over several cardiac cycles (time-averaged velocity [TAV]) and vessel cross-sectional area (A) measured from the B-mode image: Vf = TAV x A. Fourteen anesthetized baboons were studied with a duplex scanner with a 7 MHz imaging transducer and 5 MHz pulsed Doppler. B-mode ultrasound measurements of external iliac artery diameters (2.5 +/- 0.2 mm) were used for calculation of cross-sectional area. Timed blood collections obtained through a cannula inserted into the common femoral artery and TAV measurements were obtained simultaneously during 6 to 15-second intervals. These measurements were repeated three to five times per animal with different flow rates each time. Flow rates ranged from 56 to 280 ml/min (170 +/- 54 ml/min). Average velocity was 55 +/- 17 cm/sec. There was no significant difference between the two methods of volume flow measurement (Student t test). Linear regression analysis revealed a high degree of correlation (r = 0.90, slope 0.95, and p = 0.0001). The absolute percentage error was 13% +/- 8%. Volume flow measured by duplex scanning correlates highly with timed blood collections. This method has potential application for the evaluation of diseased arteries and bypass grafts whose rates of flow and waveform patterns are similar to those of this experiment.

Animals↗
PubMed1991

The effects of oral nifedipine on hepatic blood flow in humans.

Duplex ultrasonography was used to measure changes in hepatic blood flow in 13 healthy volunteers after they received single doses of 10 mg oral nifedipine and placebo. Blood flow was measured in the hepatic artery and branches of the portal and hepatic veins at baseline and 0.3, 0.6, 1, 1.5, 2, 3, 4, and 5 hours after drug administration. Cardiac output was also measured at baseline and 1, 2, and 3 hours after dosing. Blood flow initially increased in all three vessels 0.6 hour after administration of nifedipine (29%, 56%, and 31% in the hepatic artery, hepatic vein, and portal vein, respectively) compared with placebo. Flow rapidly returned to baseline in the hepatic artery and hepatic vein, whereas it appeared to remain elevated through 3 hours in the portal vein. Nifedipine administration resulted in an increase in cardiac output of 26%, 22%, and 14% above placebo at 1, 2, and 3 hours, respectively. No significant differences were detected in the systolic, diastolic, or mean arterial blood pressures after nifedipine or placebo. This study demonstrates that nifedipine increases hepatic blood flow in a transient nature and systemic hemodynamic parameters do not necessarily reflect specific organ responses. The nifedipine-induced change in blood flow should be considered when nifedipine is coadministered with high-clearance drugs, because systemic availability may be increased.

Administration, Oral↗
PubMed1991

Disposition of drugs in cystic fibrosis. II. Hepatic blood flow.

To determine whether the increased clearance of high extraction-ratio drugs in cystic fibrosis is caused by an increase in hepatic blood flow, the blood flow in main branches of the hepatic vein and portal vein was measured by use of noninvasive duplex ultrasound scanning in 10 adult subjects with cystic fibrosis and in 10 healthy age-, gender-, and height-matched control subjects. No statistically significant differences between subjects with cystic fibrosis and control subjects were detected in either the hepatic vein (217 +/- 103 ml/min for subjects with cystic fibrosis versus 211 +/- 135 ml/min for control subjects) or the portal vein (205 +/- 114 ml/min for subjects with cystic fibrosis versus 190 +/- 101 ml/min for control subjects) blood flows. These data indicate that a large (greater than or equal to 100%) increase in the clearance of high extraction-ratio drugs in patients with cystic fibrosis is unlikely to be primarily caused by an increase in hepatic blood flow. It is probable that alternative mechanisms such as enhanced secretory or metabolic pathways account in large part for increases in clearance of high extraction-ratio drugs.

Adolescent↗
PubMed1991

Primary pancreatic tuberculosis.

A 71-year-old man developed weight loss, nausea, and night sweats. A PPD skin test was positive; chest films were normal. Abdominal computerized tomography revealed a mass in the head of the pancreas. Laparotomy revealed a 3 cm by 5 cm multi-loculated abscess cavity. Cultures grew Mycobacterium tuberculum. The diagnostic criteria for abdominal tuberculosis include skin test positivity, localized disease, and culture verification. This is the first reported case that fulfills diagnostic criteria for primary pancreatic tuberculosis.

Aged↗
PubMed1990

Estimation of hepatic blood flow in branches of hepatic vessels utilizing a noninvasive, duplex Doppler method.

The measurement of hepatic blood flow by indirect methods such as indocyanine green clearance has several limitations. The duplex Doppler offers the potential for noninvasive, real-time measurement of blood flow and has been employed in the evaluation of arterial disease in a variety of vascular beds. We evaluated Doppler ultrasound estimation of blood flow in branches of the hepatic artery, hepatic vein, and portal vein in 12 healthy subjects on two separate days. In vitro accuracy of the scanner was assessed using phantom targets of known diameter and velocity. Blood velocity and vessel diameter measurements were obtained five times over a period of 2 hours. No significant differences were seen in velocity or blood flow measurements within or between days. The interday coefficients of variation, which include intrasubject variability, were 10-15% and 14-20% for velocity and blood flow measurements, respectively. This study demonstrates the potential utility of Doppler ultrasound to detect intrinsic, drug, or disease-induced changes in hepatic blood flow.

Adult↗
PubMed1990

Single and multiple doses of oral cimetidine do not change liver blood flow in humans.

Liver blood flow was measured in 10 healthy men for 6 hours after single (300 mg) and multiple (300 mg every 6 hours for 5 days) oral doses of cimetidine. Blood flow measurements were determined in the superior mesenteric and hepatic arteries and in the intrahepatic branches of the portal and hepatic veins by use of a duplex Doppler ultrasound technique. Compared with baseline measurements obtained before drug administration, cimetidine treatment did not change blood flow in any of the four blood vessels. Cimetidine serum concentrations and pharmacokinetic parameters were similar to those reported in other studies conducted in healthy adults. The findings of this study indicate that single and multiple 300 mg doses of oral cimetidine do not change liver blood flow.

Administration, Oral↗
PubMed1990

Procainamide-cimetidine drug interaction in elderly male patients.

Thirty-six hospitalized male patients receiving oral sustained-release procainamide every six hours for the treatment of ventricular arrhythmias were studied at steady-state before and after oral cimetidine 300 mg every six hours for three days. Average age and weight were 73 +/- 12 (SD) years and 76 +/- 10 kg. Patients did not have a myocardial infarction within the last two years or congestive heart failure and had calculated creatinine clearances (CrCl) between 35 and 75 mL/min/70 kg. Ten patients had urine collections that permitted computation of the ratio between the renal clearance of procainamide and CrCl (PA/CrCl) and the renal clearance of n-acetyl-procainamide (NAPA) and CrCl (NAPA/CrCl). The average steady-state procainamide and NAPA concentrations increased 55% and 36%, respectively, during cimetidine treatment (P less than .01). Twelve patients experienced mild to severe symptoms of what may have been procainamide toxicity. Apparent procainamide oral clearance decreased 41% while patients received cimetidine (P less than .01). PA/CrCl and NAPA/CrCl ratios decreased by 33% and 21%, respectively, during cimetidine therapy (P less than .05). Cimetidine therapy given to older male patients taking procainamide can cause steady-state concentrations of procainamide to rise to toxic levels. Patients prescribed this combination should be monitored carefully for adverse side effects.

Aged↗
PubMed1989

Glipizide pharmacokinetics: effects of age, diabetes, and multiple dosing.

Aging and disease may contribute to alterations in drug pharmacokinetics. The purpose of this study was to determine the effects of aging, the presence of NIDDM, and multiple dosing on the pharmacokinetics of glipizide, an oral hypoglycemic drug. Ten healthy young men (under age 25), ten healthy older men (over age 65) and 15 older diabetic men ingested a single 5 mg tablet of glipizide after an overnight fast. Blood samples for measurement of serum glipizide were obtained over the next 24 hours. The study was repeated in the diabetics after 2 weeks of daily therapy. The mean values for Tmax (range 2.0-2.5 hours), Cmax (385-465 micrograms/l), and t1/2 (4.0-4.2 hours) were not significantly different in the three populations after single doses of glipizide. Several subjects in each population had slow absorption, with peak concentrations delayed for up to 12 hours. Only one elderly diabetic subject had evidence of drug accumulation at steady state. AUC, Cl, Vss and V area were not significantly different in the three populations or at steady state, but there was a trend for AUC to be smaller and each of the other parameters to be increased in the older diabetics. The young subjects had a significantly higher fp (0.83%) than either of the two elderly groups (0.55-0.64%), but Cl int did not differ between groups. Age, diabetes, and multiple dosing appear to have little effect on the pharmacokinetics of glipizide and should have little influence on the clinical response to this drug.

Adult↗
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↗