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Biomedical subjects

V P Gotz

Publications and source records attributed to V P Gotz.

At least 19 recordsLinked to original sources
PubMed1988

Cimetidine does not increase alpha 1-acid glycoprotein serum concentrations.

Serum concentrations of alpha 1-acid glycoprotein (AAG) were studied in six healthy, male volunteers before and after administration of cimetidine, 300 mg by mouth every 6 h for 2 days. Serum AAG concentrations were measured at three different times during the first day, i.e. before cimetidine administration, and on the fourth and sixth days, after commencing cimetidine administration. Neither cimetidine treatment nor time of day contributed significantly to differences in serum AAG concentration, and no interaction of these factors was observed. It is concluded that altered drug-AAG binding as a result of cimetidine therapy is not likely to be an important mechanism contributing to cimetidine drug interactions.

Adult↗
PubMed1987

Serum lidocaine concentrations following application to the oropharynx: effects of cimetidine.

Solutions of lidocaine hydrochloride are widely used for anesthesia of the oropharynx and respiratory tract prior to endoscopic procedures. It is commonly believed that this route of administration is not associated with clinically significant systemic absorption of the drug, and large doses of topical lidocaine are routinely used in this setting. Serious adverse effects, including seizures, occasionally occur. The extent of absorption of lidocaine from the oropharynx was studied in eight healthy volunteers. Wide variation in serum lidocaine concentrations was observed. A 14-fold range of peak lidocaine concentrations occurred following identical, accurately metered doses of a lidocaine aerosol spray preparation. The effects of cimetidine on lidocaine pharmacokinetics were also studied. Therapeutic doses of oral cimetidine significantly increased the area under the lidocaine time-concentration curve (p = 0.019), but no effect on the terminal-phase elimination rate constant was observed. Serum concentrations of alpha 1-acid glycoprotein, a major binding protein of lidocaine, were significantly elevated following cimetidine (p = 0.030). Maximum lidocaine concentration, time to reach maximum concentration, and mean residence time of lidocaine were unchanged following cimetidine. These observations suggest an effect of cimetidine on the volume of distribution of lidocaine. Because of the wide variability in lidocaine pharmacokinetics and the potentially serious nature of adverse reactions, caution is advised in the use of topical lidocaine solutions in "standard" doses.

Administration, Topical↗
PubMed1987

Almitrine bismesylate.

Almitrine bismesylate is a pharmacologically unique respiratory stimulant. It enhances respiration after both acute and chronic administration by acting as an agonist of peripheral chemoreceptors located on the carotid bodies. In comparison with traditional central-acting respiratory stimulants, almitrine has advantages of oral activity, prolonged duration of effect, and an improved adverse effect profile. Almitrine is generally well tolerated, with headache and minor gastrointestinal disturbances being the most frequently observed side effects. This investigational agent has been shown to increase arterial oxygen tension while decreasing arterial carbon dioxide tension in patients with chronic obstructive pulmonary disease both at rest and during exercise through increased ventilation and improved ventilation/perfusion matching. It may also prove useful in the treatment of nocturnal oxygen desaturation because of its ability to reduce the frequency and severity of nocturnal hypoxemia without impairing the quality of sleep. Additional research is needed to further define the role of almitrine in the relief of hypoxemia.

Adult↗
PubMed1986

Lack of clinically significant in vitro and in vivo interactions between ranitidine and sucralfate.

The hypothesis that the cytoprotective agent sucralfate (sucrose octakis(hydrogen sulfate)-aluminum complex) interacts with the H2-antagonist ranitidine (N-[2-[[dimethylamino)methyl]furfuryl]- thio]ethyl]-N'-methyl-2-nitro-1,1-ethenediamine) by decreasing ranitidine absorption was tested in vitro and in vivo. The in vitro results show that ranitidine may bind to a small extent (approximately 10%) to sucralfate paste in the gastrointestinal fluids. The in vivo ineraction of 150 mg of ranitidine and 1 g of sucralfate was evaluated in a crossover study in six healthy volunteers. The results indicate no significant difference in pharmacokinetic parameters when ranitidine was given alone and in combination with sucralfate. Thus, ranitidine bioavailability is not diminished by sucralfate and the two drugs can be given concomitantly. For the determination of bioavailability, it has to be taken into account that renal clearance of ranitidine is lower after oral than after intravenous administration, and that enterohepatic recirculation of the drug is likely.

Adult↗
PubMed1986

Evaluation of tetracycline on theophylline disposition in patients with chronic obstructive airways disease.

Theophylline is a commonly used bronchodilator in the treatment of chronic obstructive airways disease (COAD) with a narrow therapeutic range of 10 to 20 micrograms/ml. Patients with COAD frequently receive concomitant antibiotic therapy for respiratory infections. This study evaluated the effect of tetracycline therapy on theophylline disposition in adults with COAD. Six males (five nonsmokers) with obstructive ventilatory defects were studied in two phases: control, after receiving sustained-release theophylline in the same dosage regimen for four days, and treatment, after receiving tetracycline 250 mg po qid for five days in addition to theophylline. During each phase, 10 blood samples were obtained over one dosing interval and analyzed for theophylline content. The following pharmacokinetic parameters were calculated: Cmin, Cmax, Css, percentage fluctuation and Cl. Differences for each value were tested as paired data with Student's two-tailed t-test. When all patients were evaluated, the only statistically significant difference was for Cmax. However, when the five nonsmokers were evaluated separately, differences were observed for Css (micrograms/ml; mean +/- SD) 9.3 +/- 3.0, control, and 10.6 +/- 3.8, treatment (p = 0.041); and for Cl [( ml/h]/kg; mean +/- SD) 49.0 +/- 11.1, control, and 43.6 +/- 10.2, treatment (p = 0.019). This study demonstrates that tetracycline may weakly inhibit theophylline clearance in nonsmoking adults with COAD.

Adult↗
PubMed1986

Evaluation of the asthmogenicity of propafenone, a new antiarrhythmic drug. Comparison of spirometry with methacholine challenge.

Propafenone is a new membrane-stabilizing antiarrhythmic agent that structurally resembles the beta-adrenergic receptor antagonist, propranolol. To determine the potential asthmogenicity of this new drug, pulmonary function, airway reactivity to methacholine, blood pressure, the electrocardiogram, and plasma concentrations were measured in 12 patients with mild intermittent asthma after 48 to 72 hours of treatment with placebo and with oral propafenone in low dosage (150 mg every eight hours) and high dosage (300 mg every eight hours) in a double-blind crossover manner. The forced vital capacity (FVC), forced expiratory volume in one second (FEV1), forced expiratory flow over the middle half of the FVC (FEF25-75%), heart rate, and blood pressure during the three regimens of treatment were not significantly different; however, the QRS interval on the ECG was significantly widened with both dosages of active drug, and the mean provocative dose of methacholine (+/- SE) required to reduce FEV1 by 20 percent (PD20) decreased from 3.0 +/- 0.6 mg/ml with placebo to 2.1 +/- 0.7 mg/ml with the high dosage of propafenone (p less than 0.01). The mean PD20 on the low-dose regimen was not significantly different from placebo or high-dose therapy. A potentially relevant increase in airway reactivity, as measured by a ratio of less than 0.5 for PD20 after treatment to PD20 after placebo, occurred in seven subjects with high-dose and in one subject during low-dose treatment (p less than 0.01). These data suggest that propafenone should be used with caution in patients with asthma and that bronchial provocation will provide a more sensitive measure of the asthmogenicity of a drug with beta-adrenergic receptor antagonist activity than pulmonary function tests. Moreover, use of bronchial provocation allows the selection of subjects with mild disease, thus reducing the risk of potentially severe bronchospasm.

Adult↗
PubMed1985

Ranitidine-associated hallucinations.

Adverse reactions involving the central nervous system have been rarely reported with ranitidine, a H2-receptor antagonist. A 72 year old female is described that developed visual hallucinations shortly after initiation of ranitidine therapy. Rechallenge with the drug resulted in both visual and auditory hallucinations following a single dose.

Aged↗
PubMed1985

Effect of a lactobacillus preparation on the absorption of oral ampicillin.

Lactobacillus preparations have been demonstrated to be beneficial in the prevention of antibiotic-associated diarrhea resulting from ampicillin. Since the bioavailability of oral ampicillin is known to be affected by food and fluid volume, a study to evaluate the influence of a lactobacillus product on ampicillin bioavailability was performed. Twelve healthy volunteers, male and female, were studied in a randomized three-way cross-over study. Each received ampicillin alone, ampicillin with a lactobacillus preparation, and ampicillin followed 1 h later by the lactobacillus preparation. Blood was sampled over a 6-h time period. Ampicillin content was determined by high-pressure liquid chromatography. Area under the concentration-time curve, area under the first moment of the concentration-time curve, maximum concentration of drug in plasma, time to maximum concentration of drug in plasma, and mean residence time were determined for each study interval. No differences in maximum concentration of drug in plasma, time to maximum concentration of drug in plasma, area under the concentration-time curve, or mean residence time were seen for either males or females or the combined group. The lactobacillus preparation as used in this study did not appear to interfere with the bioavailability of oral ampicillin.

Administration, Oral↗
PubMed1985

Ipratropium bromide.

Research clarifying the role of the parasympathetic nervous system in the pathophysiology of chronic obstructive pulmonary disease (COPD) has renewed interest in anticholinergic therapy of these disease processes. The investigational agent ipratropium bromide produces bronchodilation by competitive inhibition of cholinergic receptors on bronchial smooth muscle, antagonizing the action of acetylcholine. When administered via inhalation at therapeutic doses of 20-40 micrograms, ipratropium is somewhat less effective than beta-agonists in asthmatics. In the treatment of chronic bronchitis, however, ipratropium appears at least as effective as, and possibly superior to, the sympathomimetics. Combination therapy with beta-agonists or theophylline has resulted in enhanced effect over single-agent regimens. Due to the low serum concentrations achieved following inhalation, ipratropium has been well tolerated and is virtually free of significant adverse reactions. The primary role of ipratropium in therapy remains to be defined but appears to be as an alternative to beta-agonists in patients who fail to respond or who experience troublesome side effects. In addition, combination therapy may prove to be another important use of ipratropium in the management of COPD.

Animals↗
PubMed1985

Seizures following oral lidocaine for esophageal anesthesia.

Lidocaine is absorbed from mucous membranes of the oropharynx, gastrointestinal tract, and tracheobronchial tree. First-pass hepatic metabolism of the drug greatly reduces the amount reaching the general systemic circulation in the normal individual. In patients whose hepatic metabolism is reduced by disease or drugs, or in whom liver blood flow is reduced, this first-pass effect is decreased and lidocaine concentrations may be higher than those produced by the same dose in normal patients. We report an elderly man taking cimetidine with congestive heart failure in whom the accidental ingestion of lidocaine solution for esophageal anesthesia was followed by seizures and elevated serum lidocaine concentrations.

Aged↗
PubMed1985

Effect of filtering amphotericin B infusions on the incidence and severity of phlebitis and selected adverse reactions.

This study evaluated the effectiveness of filtering amphotericin B (ampho B) on the incidence and severity of drug-related complications. Fifteen males receiving ampho B via peripheral vein infusion participated in this randomized, double-blind study. Each patient had his dose of ampho B diluted in 500 ml of dextrose 5% in water, to which hydrocortisone 25 mg was admixed and infused over four to six hours. Eight patients had their ampho B infusions filtered through a 1 micron filter after preparation, while seven patients did not have their ampho B infusions filtered. Patients were evaluated daily for phlebitis and selected adverse effects. The two groups were comparable with regard to diagnosis, concomitant drugs, cannula type and size, vein selection, and frequency of iv site change. Four patients in each group developed phlebitis. Statistical testing using the Mann-Whitney U test revealed no difference between groups with regard to patient age, dose of ampho B, frequency and severity of phlebitis, time to onset of initial phlebitis, and frequency of adverse effects (fever, chills, headache, nausea, vomiting, and anorexia). Filtration of ampho B infusions using a 1 micron filter does not appear to decrease the incidence or severity of phlebitis and associated adverse effects.

Adult↗
PubMed1984

Dose-dependent kinetics of theophylline in adults with pulmonary diseases.

The incidence of dose-dependent pharmacokinetics of theophylline was retrospectively investigated in adults with pulmonary disease receiving continuous aminophylline infusions. Twenty-one of 180 successive admissions to medical intensive care units with a diagnosis of chronic obstructive pulmonary disease, asthma, or respiratory failure met the criteria of two steady-state serum theophylline concentrations on two different doses. Of these, 14 patients continued to smoke, whereas 7 had never smoked or had stopped greater than 1 year prior to admission. No statistical difference existed between the mean systemic clearances of theophylline at the two different doses, using either total body weight or ideal body weight. Only 1 of the 21 patients met the criteria for dose dependency of a greater than or equal to 50% reduction in clearance with dosage increase. Six of eight subjects with decreased clearance on the higher dose were nonsmokers. In contrast, all nine with augmented clearance following dosage increase were smokers. Four were considered to have proportional changes. In general, nonsmoking patients tended to have greater changes in serum theophylline concentration than in dosage. Conversely, smoking patients demonstrated smaller changes in concentration. The relationship of smoking status and dose-dependent theophylline elimination is discussed.

Adult↗
PubMed1983

Evaluation of the "condition correction factor" method of estimating theophylline clearance.

The predictive ability of the "condition correction factor" method of estimating total body theophylline clearance as proposed by Powell et al. was evaluated in 22 acutely ill hospitalized patients. Actual theophylline clearance was calculated while the patient was on a constant infusion of aminophylline with serum theophylline concentrations obtained at steady-state conditions. Independently, theophylline clearance was estimated for each patient using condition correction factors. The relationship between actual and estimated total body theophylline clearance was evaluated using multiple regression analysis and correlation testing. The data failed to demonstrate any significant positive correlation between actual and estimated theophylline clearance data. Because of this poor correlation, the use of one of the clearance estimation methods incorporating two serum theophylline concentrations obtained early in therapy is preferable, although less convenient. All estimates of clearance must be considered only as guides for individualization of therapy. Serum concentration monitoring and clinical response of the patient must be considered prior to adjustment of dosage.

Adult↗
PubMed1983

Recurrence of intravenous-diazepam-induced phlebitis from oral diazepam.

A patient who developed phlebitis from the intravenous administration of diazepam is described. This episode resolved in two days after treatment with moist heat packs. Three days after complete resolution, the phlebitis recurred approximately eight hours after a single oral dose of diazepam. This recurrence of phlebitis resolved slowly over seven days, with warm soaking and aspirin therapy. Oral diazepam may have exacerbated the initial phlebitis by interfering with a subclinical healing process.

Administration, Oral↗
PubMed1982

Computer-simulated conversion from intravenous to sustained-release oral theophylline.

A computer equipped with a pharmacokinetic program was used to theoretically determine the proper time to administer the first dose of a commonly prescribed, sustained-release oral theophylline product (Theo-Dur) in patients maintained on a continuous intravenous aminophylline infusion. Four conversion methods were tested. They included giving the first oral dose (1) immediately upon discontinuation of the iv infusion, (2) two hours after discontinuing the iv infusion, (3) four hours after discontinuing the iv infusion, and (4) two hours before discontinuing the iv infusion. Each of the four methods was simulated in three groups of patients: smokers, nonsmokers, and patients with cirrhosis. Results showed that, in most situations, given the first oral dose immediately upon discontinuation of the intravenous infusion provided minimal deviation from eventual steady-state levels. In addition, this computer simulation suggests that the initial 12-hour maintenance dose recommended by the FDA may result in toxicity in certain patient groups.

Administration, Oral↗