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Biomedical subjects

R A Prince

Publications and source records attributed to R A Prince.

At least 19 recordsLinked to original sources
PubMed1995

Safety, plasma concentrations, and efficacy of high-dose fluconazole in invasive mold infections.

A trial of the antifungal triazole fluconazole was conducted in cancer patients with presumed or proven mold infection. Groups of patients received fluconazole at four dosages (800, 1200, 1600, or 2000 mg/day). Adverse events, plasma levels, and clinical response were examined. Thirty-nine patients were enrolled. The 28 evaluable patients had presumed (13 patients) or proven (15) mold infection with Aspergillus (4) and Fusarium (3) species, Zygomycetes organisms (1), or nonspeciated mold (7). Adverse effects included elevated liver function test results (8 patients), nausea and vomiting (2), and erythema multiforme (1). Neurologic toxicity occurred in 3 patients receiving 2000 mg/day. Average steady-state peak plasma concentrations were 51.8, 74.4, and 91.8 mg/L for dosages 1200, 1600, and 2000 mg/day, respectively. Seven of 28 evaluable patients responded. Response did not appear to be related to dose. Fluconazole is well tolerated at total daily doses up to 1600 mg. The data suggest a linear plasma concentration-dose relationship. The activity of fluconazole in refractory mold infections seems to be limited.

Adolescent↗
PubMed1995

The effect of urgency on patient satisfaction and future emergency department choice.

Satisfaction with various aspects of a hospital visit may affect a patient's decisions about future patronage. Relationships between aspects of satisfaction, future use, and referral intentions, moderated by urgency, are explored in this study of 493 privately insured individuals. Results confirm the strong association between satisfaction and future intentions already established for other medical services and support increased attention to interactive marketing in medical settings.

Emergency Service, Hospital↗
PubMed1993

The retinoid X receptor enhances the function of the peroxisome proliferator activated receptor.

The peroxisome proliferator activated receptor (PPAR) is a member of the steroid hormone receptor superfamily and is activated by a variety of non-genotoxic rodent hepatocarcinogens termed peroxisome proliferators. A key marker of peroxisome proliferator action is the peroxisomal enzyme acyl-CoA oxidase that is elevated about 10-fold in the liver of treated rodents. We have shown previously that a peroxisome proliferator response element (PPRE) is located 570 bp upstream of the rat acyl-CoA oxidase gene and that PPAR binds to it. We show here that the retinoid X receptor (RXR) is required for PPAR to bind to the PPRE and that the RXR ligand, 9-cis retinoic acid, enhances PPAR action. These results therefore suggest that retinoids may modulate the action of peroxisome proliferators.

Acyl-CoA Oxidase↗
PubMed1993

Pharmacokinetics of cefepime in cystic fibrosis patients.

The purposes of this study were to determine and compare the single- and multiple-dose pharmacokinetics of cefepime in patients with and without cystic fibrosis. Twelve patients with cystic fibrosis hospitalized for treatment of acute pulmonary exacerbations were studied. In addition, pharmacokinetic data for seven of the patients with cystic fibrosis were compared with those for seven age-matched control patients. The cefepime dose was 50 mg/kg of body weight (maximum, 2 g) administered as a 30-min intravenous infusion every 8 h for a minimum of 8 days. Serial plasma and urine samples, obtained after the first and last doses, were analyzed for cefepime content by a validated high-pressure liquid chromatographic assay. By standard noncompartmental analysis, the pharmacokinetic parameters ascertained were area under the concentration in plasma-time curve, elimination half-life, total body clearance, renal clearance, and volume of distribution at steady state. In addition, the maximum concentration in plasma was recorded. Mean (+/- standard deviation) results of the first dose analysis in patients with cystic fibrosis were as follows: maximum concentration in plasma, 142.6 (+/- 26.07) micrograms/ml; area under the concentration in plasma-time curve, 265.3 (+/- 114.31) micrograms.h/ml; elimination half-life, 1.8 (+/- 0.53) h; total body clearance, 127.2 (+/- 50.94) ml/min; renal clearance, 91.1 (+/- 38.86) ml/min/kg; volume of distribution at steady state, 14.1 (+/- 4.31) liters. Analysis for the last dose in patients with cystic fibrosis did not vary appreciably from these values, nor did those from the controls. Thus, it appears that the first-dose pharmacokinetics of cefepime are predictive of those at steady state. In order to consistently exceed the MIC for Pseudomonas aeruginosa for the entire dosing interval in patients with cystic fibrosis, a higher dose and/or different dosing interval compared with those used in this study may be necessary.

Adolescent↗
PubMed1993

The peroxisome proliferator-activated receptor:retinoid X receptor heterodimer is activated by fatty acids and fibrate hypolipidaemic drugs.

The peroxisome proliferator-activated receptor (PPAR) is a member of the steroid hormone receptor superfamily and is activated by a variety of fibrate hypolipidaemic drugs and non-genotoxic rodent hepatocarcinogens that are collectively termed peroxisome proliferators. A key marker of peroxisome proliferator action is the peroxisomal enzyme acyl CoA oxidase, which is elevated about tenfold in the livers of treated rodents. We have previously shown that a peroxisome proliferator response element (PPRE) is located 570 bp upstream of the rat peroxisomal acyl CoA oxidase gene and that PPAR binds to it. We show here that the retinoid X receptor (RXR) is required for PPAR to bind to the PPRE, and that the RXR ligand, 9-cis retinoic acid, enhances PPAR action. Retinoids may therefore modulate the action of peroxisome proliferators and PPAR may interfere with retinoid action, perhaps providing one mechanism to explain the toxicity of peroxisome proliferators. We have also shown that a variety of hypolipidaemic drugs and fatty acids can activate PPAR. This supports the suggestion that the physiological role of PPAR is to regulate fatty acid homeostasis, and provides further evidence that PPAR is the target of the fibrate class of hypolipidaemic drugs. Finally, we have demonstrated that a metabolically stabilized fatty acid is a potent PPAR activator, suggesting that fatty acids, or their acyl CoA derivatives, may be the natural ligands of PPAR.

Animals↗
PubMed1992

Stability of ondansetron hydrochloride in injectable solutions at -20, 5, and 25 degrees C.

The stability of ondansetron hydrochloride in 5% dextrose injection and in 0.9% sodium chloride injection when stored frozen, refrigerated, and at room temperature was studied. Solutions of ondansetron 0.03 and 0.3 mg/mL (as the hydrochloride salt) were prepared by adding 1.5 or 15 mg of the drug to 50-mL minibags containing 5% dextrose injection or 0.9% sodium chloride injection. All solutions were prepared in triplicate, and each container was tested in duplicate. Testing at the time of preparation and at each subsequent test interval included visual inspection of color and clarity, determination of pH, and a stability-indicating high-performance liquid chromatographic assay to measure the ondansetron concentration. Conditions assessed included storage at -20 degrees C for two weeks to three months, 5 degrees C for 7-14 days, approximately 25 degrees C for up to 48 hours, and various combinations of these conditions. The concentration of ondansetron in each solution remained above 90% of the original concentration at each observation time under all storage conditions. No changes in color or clarity were observed, and there were only minor changes in pH. Ondansetron 0.03 and 0.3 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection was stable when stored (1) for up to three months at -20 degrees C, followed by up to 14 days at 5 degrees C and by 48 hours at 25 degrees C and (2) for up to 14 days at 5 degrees C, followed by up to 48 hours at 25 degrees C.

Drug Stability↗
PubMed1991

Alpha interferon gene deletions in adults, children and infants with acute lymphoblastic leukemia.

DNA from 76 cases of acute lymphoblastic leukemia (ALL) was tested with a cDNA probe encoding the alpha 2B interferon (IFN) gene transcript. Deletions were found in three of ten pre-B, three of 21 T-cell, four of 22 common and one of 23 null ALL cases. Amongst those with null ALL were 20 infants, most with characteristic translocations, none of whom had deletion of alpha IFN genes. The results confirm that alpha IFN gene deletions may occur without visible abnormalities of chromosome 9p and show that they occur across a wide range of ALL phenotypes. The results suggest that alpha IFN gene deletions may be rare events in null ALL of infants but their incidence and cellular consequences remain unknown.

Adult↗
PubMed1989

Effect of quinolone antimicrobials on theophylline pharmacokinetics.

The purpose of the research was to ascertain the comparative differences of quinolone antibiotics on theophylline pharmacokinetics. Eight healthy male volunteers were randomly assigned to four treatments. Each was administered norfloxacin (NOR) 800 mg/d, ciprofloxacin (C) 1 g/d, nalidixic acid (NAL) 2 g/d and placebo (P) for 7 days. On the seventh day of each treatment, theophylline (5 mg/kg) iv was administered. The elimination half-life (T 1/2), total body clearance (CL) and volume of distribution at steady state (Vss) of theophylline were calculated using model-independent methods. ANOVA for repeated measures was used for data comparisons. The mean (SD) theophylline results were: CL l/kg/h--NOR .038 (.006), C .033 (.006), NAL .045 (.008), P .044 (.007); T 1/2 h--NOR 9.2 (1.8), C 10.6 (1.8), NAL 8.3 (1.8), P 7.5 (1.4). Theophylline Vss differences by treatment were not significant. NOR and C significantly decreased theophylline's clearance and the clearance change can be of clinical significance.

Adult↗
PubMed1989

Influence of endotoxin-induced fever on the pharmacokinetics of theophylline in the rabbit model.

To assess fever-induced changes in theophylline pharmacokinetics in the rabbit model, six healthy, male, New Zealand white rabbits were studied using a randomized, matched-pair design. In treatment 1, 15 mg/kg of theophylline was infused into the left marginal ear vein, and several blood samples were collected from the opposite ear for 10 hours. Treatment 2 was conducted in an identical manner, except 20 to 40 micrograms/kg of Escherichia coli endotoxin was injected into the left marginal ear vein to induce fever. The majority of the rabbits had slight decreases in the slowest disposition rate constant and increases in the volume of distribution at steady state; however, total body clearance was only minimally (5%) changed. No statistically significant differences were noted between these values (Hotelling T2 = 0.32). Given the sample and methods, fever apparently does not affect theophylline pharmacokinetics.

Animals↗
PubMed1987

Penetration of cefotaxime into respiratory secretions.

The objective of this study was to quantitate cefotaxime and its active metabolite, desacetyl cefotaxime, in the distal airways and to compare these levels to concentrations in plasma. Respiratory secretions were obtained from the subsegmental level in 17 adult patients undergoing fiber-optic bronchoscopy within 2 h after receiving four doses of cefotaxime (2 g intravenously every 6 h). In 11 patients, cefotaxime levels measured by high-pressure liquid chromatography in bronchial secretions were below detectable limits (less than 0.5 mg/liter); however, levels of desacetyl cefotaxime exceeded 1.5 mg/liter in 9 of these 11 patients (range, 1.6 to 10 mg/liter). Concentrations of desacetyl cefotaxime in lung secretions (6.9 +/- 0.85 [standard error] mg/liter) was 77% of mean levels of desacetyl cefotaxime in plasma (8.9 +/- 1.26 mg/liter). In summary, concentrations of desacetyl cefotaxime in bronchial secretions are markedly higher than those of cefotaxime.

Adult↗
PubMed1986

Effects of smoking on nortriptyline plasma concentrations in depressed patients.

The pharmacokinetic parameters of half-life, volume of distribution, and steady-state nortriptyline plasma concentration normalized to a 100-mg/day maintenance dose were calculated in nine smokers and 15 nonsmokers. The mean normalized total nortriptyline concentration for the smokers of 118 +/- 33 ng/ml was significantly lower than the nonsmokers' mean value of 158 +/- 35 ng/ml. The mean normalized free plasma concentrations for the smokers of 11.4 +/- 3.5 ng/ml was not different from the nonsmokers' mean concentrations of 11.5 +/- 2.6 ng/ml. The smokers had a slightly higher percentage free drug values of 10.2 +/- 4.0% (p = 0.08) as contrasted to 7.4 +/- 1.5% free nortriptyline for the nonsmokers. The nortriptyline half-life figures for both the free and total drug concentrations did not differ. Multiple linear regression analysis utilizing age, smoking status, sex, liver function, and the presence or absence of enzyme-inducing or -inhibiting drugs as the potential independent variables and percentage free nortriptyline or total nortriptyline concentration as the dependent variable, found that smoking status explained 21% of the variation in the percentage free nortriptyline in the patients and 26% of the variation in the total nortriptyline concentrations. These preliminary data suggest that smokers ideally should be dosed at the lower end of the nortriptyline therapeutic range, whereas nonsmokers should be dosed at the upper end to maximize the antidepressant effect and minimize adverse effects.

Adolescent↗
PubMed1986

The utility of a single-point dosing protocol for predicting steady-state lithium levels.

Two methods for predicting steady-state serum lithium level were compared prospectively in in-patients suffering from affective disorder. A single-point prospective administration model that required a single 24-hour serum lithium level, following a test dose produced statistically similar predictions of the observed steady-state lithium levels as did a model that required 12- and 36-hour levels. However, the latter two-point method produced significantly more accurate predictions from clinical interpretation. Although the two-point approach is preferable, the single-point method is clinically acceptable if its limitations of accuracy are taken into consideration.

Adult↗
PubMed1984

Prospective evaluation of two lithium maintenance dose schedules.

A prospective method for recommending lithium carbonate maintenance doses for patients requiring the drug either prophylactically or for acute mania has been previously described. Of 18 patients who required prophylactic lithium levels between 0.40 and 0.89 mEq/liter, the maintenance dose equation achieved the predefined therapeutic range in 15 (83%) cases. Of 20 patients requiring lithium concentrations between 0.90 and 1.30 mEq/liter for the treatment of acute mania, 17 (85%) attained the therapeutic range after receiving the recommended maintenance dose. The authors discuss the factors that limit the usefulness of this prospective dosing protocol.

Adult↗