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Biomedical subjects

J H Fischer

Publications and source records attributed to J H Fischer.

At least 55 records · Page 3Linked to original sources
PubMed1990

Altered theophylline metabolism in patients with psoriasis.

We observed two patients on theophylline therapy with concomitant severe psoriasis and a two- to threefold greater theophylline clearance than that reported in healthy, nonsmoking adults. There were no factors known to induce theophylline clearance. In both cases, the induction of theophylline metabolism was relatively selective for the 1-methyluric acid pathway. The altered metabolism in these patients appeared to correlate with the clinical severity of the disease. The data suggest the possibility that an observed lack of efficacy for theophylline in psoriasis may be related to pharmacokinetic effects. The concept that altered drug metabolism may occur in the presence of skin disease has important implications for pharmacotherapeutics in dermatology.

Aged↗
PubMed1990

Effect of age and training status on pharmacokinetics of flunixin meglumine in thoroughbreds.

The effect of age and training status on the pharmacokinetics of flunixin meglumine was evaluated in 16 Thoroughbreds. Horses were assigned to 1 of 3 groups on the basis of age and training status: group A (n = 6), horses in active training and less than or equal to 5 years old; group B (n = 5), horses out of training for a minimum of 6 weeks and less than or equal to 5 years old; and group C (n = 5), horses out of training for at least 2 years and greater than or equal to 9 years old. After administration of 500 mg of flunixin meglumine IV, multiple serum and urine samples were obtained over 24 hours and assayed for flunixin by high-performance liquid chromatography. Although the mean distribution rate constant and volume of distribution were similar for the 3 groups, mean total body clearance and elimination rate constant were significantly (P less than 0.05) greater and half-life significantly (P less than 0.01) less in groups A and B, compared with group C. Differences in pharmacokinetic values were not observed between the horses in group A and B. In addition, the changes in clearance, elimination rate constant, and half-life of flunixin were found to significantly (P less than 0.05) correlate with age. The results of this investigation indicated that age, but not training status, influences disposition of flunixin meglumine in Thoroughbreds.

Age Factors↗
PubMed1989

[Status of the captopril test in the diagnosis of hypertension].

The place of captopril (C) testing in the screening for renovascular hypertension is still controversial. Baseline and C-stimulated plasma renin concentrations (PRC) were measured in 113 hypertensives, who where referred for the exclusion of secondary hypertension. In addition intravenous digital subtraction angiography (DSA) and a renal scintigraphy were performed. When renal artery disease was revealed by DSA or renin was stimulated the renal arteries were visualized by direct arteriography (and treated by angioplasty if possible). 86 patients underwent each diagnostic test: 21% had renovascular hypertension. Unilateral renal artery stenosis (n = 10) was detected by the captopril test (cutoff values: baseline greater than 40 microU/ml, after C greater than 180 microU/ml, sensitivity 100%). Bilateral renal artery stenosis (n = 8) was missed when the disease was equally severe on either side (sensitivity 50%). The specificity of C testing was 82%, overall sensitivity (uni- and bilateral disease 78%, prevalence 21%, predictive value of the positive test 0.56, predictive value of the negative test 0.93). With i.v.-DSA the renal arteries were technically evaluable in 91% (82/92) of cases. The sensitivity for the detection of all renal artery stenoses was 79% (uni-lateral 100%, bilateral 40%, specificity 97%). The sensitivity of renal scintigraphy for the detection of unilateral renal artery stenoses was 50%, for the detection of bilateral renal artery stenoses 43%, specificity 81%. The present study demonstrates the usefulness of captopril for the detection of unilateral renal artery stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Nizatidine suppression of basal gastric acid output: a comparison of two intravenous dosage regimens.

To study the pharmacokinetics and pharmacodynamics of two intravenous nizatidine dosing regimens, serial plasma concentrations and continuous intragastric pH were monitored simultaneously in 10 subjects with a documented history of duodenal or gastric ulcers. A 24-hour gastric pH profile was characterized for a 300 mg daily dose of nizatidine randomly administered both as 100 mg every 8 hours and 150 mg every 12 hours. No significant differences were observed in the mean pharmacokinetic parameters between the two dosing regimens. Pharmacodynamic parameters for the 100 mg every 8 hours versus the 150 mg every 12 hours regimen were not significantly different except for percent of time during the 24-hour study period that the pH was maintained greater than 4 (43.6 +/- 20.7 versus 34.7 +/- 18.3, P less than .05). A significant relationship was demonstrated for both regimens (P less than .05) between the percent time pH greater than 4 and area under the plasma curve for the 24 hour study period. The lack of a significant difference in nizatidine pharmacokinetics between the two dosage regimens suggests a pharmacodynamic cause for the greater cumulative pH effect of the every 8 hour regimen.

Adult↗
PubMed1989

Simulation of vancomycin peak and trough concentrations using five dosing methods in 37 patients.

Five methods of dosing vancomycin (Matzke, Moellering, Nielsen, Lake-Peterson, and manufacturer's) were simulated in 37 patients. Ten serum samples were obtained after a 1-hour intravenous infusion of 6.2-20 mg/kg total body weight. A preinfusion serum sample was obtained from patients not studied on the first dose. Initial estimates of pharmacokinetic values were made using nonlinear iterative least squares regression and serum concentration-time data. These data were fitted to a two-compartment, open-infusion model. Simulations of the peak and trough serum concentrations at steady state for each patient were determined by multiple-dose simulated pharmacokinetics and each patient's pharmacokinetic values using the regimen suggested by each of the five methods. Steady-state serum concentrations, predicted systemic clearance by each method (except Lake-Peterson), and the daily dose for each patient recommended by each method were determined. All the methods underpredicted actual drug clearance, with the Nielsen method having the lowest prediction. The Matzke method recommended the largest dosage. Using each of the methods, only 3-16% of patients would have achieved recommended peak and trough serum concentrations. In the simulation model used, no method performed satisfactorily in attaining the desired vancomycin peak and trough concentrations. We suggest that the Lake-Peterson method could be used initially, provided that monitoring is also performed to adjust the dosage regimen further.

Adult↗
PubMed1988

Vancomycin pharmacokinetics in patients with various degrees of renal function.

The influence of age, protein binding, and renal function on the pharmacokinetics of intravenous vancomycin was evaluated in 37 adult patients with various degrees of renal function. Patients were categorized into three groups based on measured creatinine clearance (CLCR): groups 1, 2, and 3 had 24-h CLCRs of greater than 70, 40 to 70, and 10 to 39 ml/min per 1.73 m2, respectively. After 1 h of intravenous infusion, concentrations of vancomycin in serum declined in a biexponential manner in all patients. Diminished renal function in groups 2 and 3 was accompanied by a lower total body vancomycin clearance (CL) (52.6 and 31.3, respectively, versus 98.4 ml/min per 1.73 m2) and a lower renal vancomycin clearance (CLR) (48.2 and 19.8, respectively, versus 88.0 ml/min per 1.73 m2) than in group 1. No significant differences in apparent distribution volume of the central compartment or apparent distribution volume at steady state were observed. Mean serum protein binding of vancomycin was 30% and was not significantly affected by renal function. Stepwise multiple linear regression analysis revealed that CLCR was the strongest predictor of vancomycin CL (r = 0.77, P less than 0.001) and vancomycin CLR (r = 0.87, P less than 0.001). Age did not significantly improve these correlations once CLCR was included. The relationship of vancomycin CL and CLCR was utilized to develop the following equation to dose vancomycin in the majority of renally impaired patients: dose (milligrams per kilogram per 24 h) = 0.227CLCR + 5.67, where CLCR is standardized to milliliters per minute per 70 kg. The practical dosing intervals that the calculated dose can be divided into and administered include 8, 12, 24, and 48 h based on the CLCR of the patient.

Adult↗
PubMed1988

Serum haloperidol concentration and choreiform movements in Huntington's disease.

The relationship between serum haloperidol concentration and improvement in abnormal movements was investigated in 20 adult Huntington's disease (HD) patients. Serum samples and assessments of severity of chorea were simultaneously obtained from each patient. Data were obtained prior to and at one or more doses following the initiation of haloperidol in ten patients. Serum was analyzed for haloperidol by two different methods, gas chromatographic/mass spectrometric (GC/MS) and radioreceptor (RR) assays. Steady-state serum haloperidol concentrations (GC/MS) of 0.5 to 24 ng/ml were observed following administration of doses of 1 to 40 mg/d and varied markedly between patients. Only results from the GC/MS assay were used for examining relationships with dose and clinical response because of insensitivity of RR assay. Significant improvement of abnormal movements, greater than 30% from baseline, occurred at serum concentrations between 2 and 5 ng/ml, which corresponded to doses of 1.5 to 10 mg/d. Further improvement in abnormal movements at serum concentrations above this range was minimal.

Adult↗
PubMed1988

Effect of food on the serum concentration profile of enteric-coated valproic acid.

We evaluated the effect of food on the serum concentration profile of enteric-coated divalproex sodium (EC-VPA) in six adult volunteers following a single dose and in six patients during chronic-dose administration. The results demonstrated a significant delay but no decrease in extent of EC-VPA absorption following administration with food. To monitor serum concentrations in patients receiving EC-VPA, consideration of sampling time in relation both to time of dose and meals is required.

Adult↗
PubMed1988

Near-total reduction in verapamil bioavailability by rifampin. Electrocardiographic correlates.

We evaluated the significance of the interaction between rifampin and verapamil in six volunteers who received single doses of verapamil, 10 mg intravenously (IV), then 120 mg orally two days later. Subjects were then given rifampin, 600 mg orally every day for 15 days. After 13 and 15 days of rifampin therapy, the IV and oral doses of verapamil were repeated. Electrocardiograms (ECG) were done and serum verapamil and norverapamil concentrations measured before and for 12 h after each dose. For IV verapamil, there was a small decrease in area under the serum concentration-time curve and an increase in clearance after rifampin therapy (p less than 0.05). There were no changes in elimination half-life, volume of distribution, or AUC for percentage of change in P-R interval-time curve (AUCPR). For oral verapamil, there were marked decreases in peak concentration, AUC, oral bioavailability (all p less than 0.005), and AUCPR (p less than 0.001) after rifampin treatment. There were no changes in time to peak concentration or elimination half-life. For oral verapamil, significant P-R interval prolongation occurred only before treatment with rifampin. The decrease in oral bioavailability and the abolition of ECG response confirm that a highly significant drug interaction exists between rifampin and verapamil given orally but not intravenously.

Administration, Oral↗
PubMed1988

Stability of nizatidine in commonly used intravenous fluids and containers.

The stability of nizatidine in commonly used i.v. fluids stored in glass and plastic containers was studied. Stock solutions of nizatidine 0.75, 1.5, and 3.0 mg/mL in 15 i.v. fluids were prepared using nizatidine injection 25 mg/mL. Six 50-mL aliquots of each solution were transferred to separate glass infusion bottles and stored at room temperature or under refrigeration. Twenty-one 40-mL aliquots of additional stock solutions of nizatidine 0.75 and 3.0 mg/mL in 0.9% sodium chloride injection or 5% dextrose injection were transferred to polyvinyl chloride (PVC) bags and stored at room or refrigerated temperature; some of these solutions were frozen, thawed, and refrigerated before analysis. Samples of each admixture were analyzed after 0.5, 1, 2, 3, and 7 days of storage for nizatidine concentration using a stability-indicating high-performance liquid chromatographic assay and also for visible changes and pH. The concentration of nizatidine in each admixture remained within 92%-106% of actual initial storage concentration throughout the study period, with the exception of nizatidine 3.0 mg/mL in 8.5% amino acid injection. The stability of nizatidine in admixtures stored in polyvinyl chloride bags was similar to that of admixtures stored in glass bottles. In the i.v. fluids, concentrations, and containers studied, nizatidine admixtures are stable for at least 7 days at either room or refrigerated temperature and 30 days when stored frozen in polyvinyl chloride bags. Admixtures of nizatidine 3.0 mg/mL in 8.5% amino acid injection should not be stored at room temperature for longer than four days.

Chromatography, High Pressure Liquid↗
PubMed1988

Efficacy of individualized phenytoin sodium loading doses administered by intravenous infusion.

The safety and efficacy of administering individualized phenytoin sodium loading doses by intravenous infusion were studied on 40 occasions in 37 adult patients having seizures. Doses were calculated based on an average volume of distribution (0.75 L/kg) and desired plasma phenytoin concentration. Total and free phenytoin concentrations were determined before and after the infusion. Phenytoin sodium doses of 225-1300 mg were administered by intravenous infusion at a rate of 40 mg/min after dilution in 0.9% sodium chloride injection to concentrations ranging from 4.5 to 13.5 mg/mL. Infusion rates were reduced if adverse effects occurred. The dosing method accurately achieved desired phenytoin concentrations (predicted mean +/- S.D. concentration, 18.3 +/- 1.6 micrograms/mL; observed mean concentration, 17.4 +/- 2.5 micrograms/mL). Postinfusion concentrations of free phenytoin ranged from 0.8 to 3.6 micrograms/mL (mean +/- S.D., 1.7 +/- 0.6 micrograms/mL). Of 21 patients evaluated for efficacy, 16 responded. A total of 45% of patients experienced pain at the infusion site, which diminished when the infusion rate was reduced. No serious cardiovascular or neurological toxicities occurred. The intravenous infusion method of administration is safe and effective and is useful for rapid achievement of therapeutic phenytoin concentrations in the emergency room setting.

Adult↗
PubMed1987

Evaluation of topical metronidazole gel in acne rosacea.

Topical metronidazole gel (0.75%) was compared to placebo gel in a randomized, double-blind, placebo-controlled, split-face clinical trial for the treatment of 59 patients with acne rosacea. Statistically significant differences in inflammatory lesions, erythema, and global assessments were seen at three, six, and nine weeks post-baseline in favor of the active treatment side. It did not, however, alter the telangiectatic component of the disease. No known drug-related side effects were detected, and the low topical dose along with low serum levels of metronidazole indicate a high safety profile for this therapeutic agent. This work suggests that metronidazole gel, as specifically formulated, is safe and effective in reducing the symptomatology of acne rosacea.

Administration, Topical↗
PubMed1986

Cardiopulmonary effects of betamimetic tocolytic and glucocorticoid therapy in pregnant women.

In 35 present women, undergoing tocolytic treatment with betamimetics had intensive monitoring by balloon-tipped catheter. After the administration of 2-4 micrograms/min of fenoterol the cardiac output (CO) increased from 8.2 l/min to over 11 l/min with a corresponding increase in mean pulmonary artery pressure (MPAP) from 11.7 mmHg to over 18 mmHg. The correlation coefficient between MPAP/CO was highly significant. In the 10 patients in whom we were able to monitor pulmonary capillary pressure (PCP), we observed no significant increase to suggest compromised cardiac performance. The calculated total resistance of the pulmonary vessels (TPR) decreased during the first 24 h followed by a return to initial values. Our investigations suggest that the principal cardiovascular effect of betamimetics in pregnant women is a volume-dependent increase in pressure in the pulmonary circulation. The simultaneous administration of betamethasone had no additional effects.

Betamethasone↗
PubMed1986

Evaluation of a continual compliance monitoring program for dapsone in an outpatient Hansen's disease clinic.

Guidelines for the assessment of patient compliance to dapsone were developed and evaluated. The urinary dapsone-to-creatinine (D/C) ratio following standardization by dose, ideal body weight, and time since last dose was used for assessment of compliance. Compliance standards were established in 12 patients of known compliance and confirmed prospectively in nine inpatients on 14 occasions. Compliance increased significantly among outpatients (N = 30) attending the University of Illinois Hansen's Disease Clinic from 47% at base line to 73% at 6 months and 80% at 18 months after establishing the monitoring program. In a subgroup of 18 patients, a similar increase in compliance was observed from 50% to 80%. A good therapeutic response was seen in the subgroup patients who were compliant. A poor therapeutic response was seen in the consistently noncompliant patients. These results demonstrate that use of a continual compliance monitoring program can improve patient drug compliance in an outpatient Hansen's disease clinic.

Ambulatory Care Facilities↗
PubMed1985

Quantitative determination of tolazoline in serum and urine.

A high-performance liquid chromatographic procedure is described for the analysis of tolazoline in serum and urine. This assay procedure is suitable for the analysis of micro-samples (50 or 100 microliters serum and 100 microliters urine). Samples are extracted in a single step and injected into a reversed-phase high-performance liquid chromatography system for detection at 210 nm. The clinical applicability of this assay is demonstrated by the determination of tolazoline serum and urine concentrations in neonates. In addition, the presence of urine conjugates and the extent of serum protein binding were investigated. This assay procedure has the required sensitivity (0.1 microgram/ml), accuracy and precision for both routine monitoring and pharmacokinetic characterization of tolazoline in neonates and adults.

Chromatography, High Pressure Liquid↗