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Biomedical subjects

D E Nix

Publications and source records attributed to D E Nix.

At least 55 records · Page 3Linked to original sources
PubMed1991

Theophylline toxicity secondary to ciprofloxacin administration.

We report the case of a 79-year-old woman who presented from a skilled nursing facility to the emergency department with signs and symptoms of theophylline toxicity and a serum theophylline concentration of 53.7 mg/L. The patient had been on a regular regimen of aminophylline for two months, with the addition of ciprofloxacin three days before arrival as the only identifiable potential cause of theophylline intoxication. She was monitored and treated conservatively with serial doses of activated charcoal, which resulted in a reduction of her serum theophylline level to a therapeutic concentration in 15 hours without adverse sequelae. The number of cases of theophylline intoxication secondary to concurrent ciprofloxacin administration is likely to increase, especially in nursing home populations, and it should be suspected when these patients present to the ED with the appropriate signs and symptoms. Management of theophylline intoxication should be based on clinical presentation as well as concentrations of the drug.

Aged↗
PubMed1991

Combined use of ciprofloxacin and sucralfate.

The effect of sucralfate on the bioavailability of ciprofloxacin hydrochloride was assessed in 12 healthy male volunteers. The study was a four-period crossover design where subjects were randomized to one of four treatment sequences at entry. Treatments A, B, and C included sucralfate 2 g q12h for five doses. For treatment A, the fifth dose sucralfate was administered concurrently with ciprofloxacin 750 mg. For treatment B, 750 mg of ciprofloxacin was administered two hours before the fifth dose of sucralfate. Treatment C consisted of ciprofloxacin 750 mg six hours before the fifth dose of sucralfate. A 750-mg dose of ciprofloxacin was administered alone for treatment D. Blood and urine samples were collected at predetermined time intervals for 24 hours. Ciprofloxacin concentrations were determined by HPLC. The area under the concentration versus time curve from zero to infinity and the urinary recovery of ciprofloxacin were used for determining relative bioavailability. Concurrent administration of ciprofloxacin and sucralfate (treatment A) resulted in a significant decrease (p less than 0.05) in ciprofloxacin absorption. The relative bioavailabilities for treatments A, B, and C were 0.0429 +/- 0.0202, 0.829 + 0.21, and 0.965 + 0.32, respectively, relative to ciprofloxacin alone. In normal volunteers, ciprofloxacin may be administered between two and six hours before sucralfate, allowing sufficient time for ciprofloxacin absorption prior to the sucralfate dose and thereby minimizing the chance of a significant interaction. In patients with decreased gastric emptying the interaction may be more difficult to avoid.

Adolescent↗
PubMed1991

Pharmacokinetic simulation of the effect of multiple-dose activated charcoal in phenytoin poisoning--report of two pediatric cases.

Activated charcoal is commonly used to inhibit the absorption of phenytoin after acute overdose. There are also reports of multiple-dose activated charcoal (MDAC) increasing the clearance of phenytoin in adults. We describe our experience modeling phenytoin pharmacokinetics during therapy with MDAC in the treatment of two cases of acute phenytoin poisoning in children. After extensive attempts at modeling the serum phenytoin concentrations, simulations were performed to identify the possible consequences of MDAC administration. Phenytoin elimination was more rapid than was expected, based on previously reported phenytoin pharmacokinetic parameters. Moreover, the time to peak phenytoin concentration and time course of phenytoin intoxication appeared to be shorter than available reports of phenytoin intoxication treated with a single dose of activated charcoal. MDAC may prevent continued phenytoin absorption and increase phenytoin elimination rate via gastrointestinal dialysis. The effect of MDAC on the clearance of phenytoin can be described by a first-order elimination rate constant of approximately 0.02-0.04/h.

Charcoal↗
PubMed1991

Mathematical examination of dual individualization principles (I): Relationships between AUC above MIC and area under the inhibitory curve for cefmenoxime, ciprofloxacin, and tobramycin.

Traditional antibiotic dosage adjustments target predetermined serum concentrations, whereas a host of in vitro studies and recent clinical trials establish that bacteria vary in their susceptibility. Dual individualization, which considers the variance in both antibiotic pharmacokinetics and bacterial susceptibility, has been employed to describe different rates of bacterial eradication in relation to varying serum concentrations. In patients with nosocomial pneumonia, one of the model compounds studied was cefmenoxime, where a target six-hour area under the serum concentration-time curve (AUC) of 140 micrograms.h/mL above minimum inhibitory concentration (MIC) was previously associated with bacterial eradication in an average of four days. The target AUC value of 140 micrograms.h/mL above MIC is unique to cefmenoxime. Ideally, there should be a dual individualized target useful to adjust the dose of any antibiotic. Computer simulations performed to evaluate this hypothesis suggested that each antibiotic had a unique value for target AUC above MIC. These simulations indicated that an optimal AUC above MIC was about 80 percent of the total AUC above the MIC. Predictable rates of bacterial eradication would presumably result from maintaining these relationships across the range of bacterial susceptibility and the range of serum concentration profiles. Each antibiotic has a unique and different 24-hour AUC over MIC value associated with bacterial eradication in 4 days. For cefmenoxime, the target was 540 area units over MIC per 24 hours, tobramycin with 34 area units, and ciprofloxacin with 23 area units per 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Cefmenoxime↗
PubMed1991

Compatibility of ciprofloxacin injection with selected drugs and solutions.

The compatibility of ciprofloxacin injection with selected antimicrobials and aminophylline was studied. Ciprofloxacin, amikacin sulfate, aminophylline, clindamycin phosphate, gentamicin sulfate, and tobramycin sulfate were mixed separately in minibags containing 0.9% sodium chloride injection or 5% dextrose injection; admixtures were stored for up to 48 hours at either 4 degrees C or 25 degrees C. Ciprofloxacin was also combined separately with each of the other drugs and solutions and stored under the same conditions. In addition, ciprofloxacin was combined with metronidazole in ready-to-use mini-bags of the latter drug and stored at 25 degrees C. Drug concentrations were measured by fluorescence polarization immunoassay or high-performance liquid chromatography. All admixtures were also examined visually. Stability was defined as retention of at least 90% of the original drug concentration with no visual evidence of incompatibility. With one exception, drugs in all single-drug admixtures were stable for 48 hours. The drug concentration eight hours after amikacin was mixed in 0.9% sodium chloride and refrigerated was 89% of the original concentration. When ciprofloxacin was combined with gentamicin, metronidazole, or tobramycin, all of the involved drugs were stable for 48 hours. Compatibility of ciprofloxacin-amikacin admixtures depended on the fluid and storage temperature; all such admixtures were stable for at least eight hours. A precipitate formed immediately whenever ciprofloxacin was mixed with clindamycin and within four hours after ciprofloxacin was mixed with aminophylline. Ciprofloxacin injection was compatible with gentamicin, metronidazole, and tobramycin and incompatible with aminophylline and clindamycin. The compatibility of ciprofloxacin-amikacin admixtures depended on the i.v. solution and storage temperature.

Amikacin↗
PubMed1990

Inhibition of norfloxacin absorption by antacids.

The effect of antacids on the systemic absorption of oral norfloxacin was evaluated in 12 healthy volunteers. Subjects were given each treatment in a balanced sequence at 7-day intervals. Treatments included 400 mg of norfloxacin alone, 400 mg of norfloxacin 5 min after aluminum-magnesium hydroxide (Maalox), Maalox 2 h after 400 mg of norfloxacin, and 400 mg of norfloxacin 5 min after calcium carbonate (Titralac). Blood and urine samples were collected at predetermined time intervals for 24 and 48 h, respectively. Norfloxacin concentrations in plasma and urine were determined by high-pressure liquid chromatography. The area under the plasma concentration-versus-time curve from time zero to infinity and urinary recovery were used to compare the relative bioavailability of norfloxacin with antacids with that of norfloxacin alone. Norfloxacin bioavailability was markedly reduced when subjects received antacid pretreatment. When norfloxacin was given 5 min after Maalox and Titralac, the bioavailabilities were 9.02 and 37.5%, respectively, relative to that for 400 mg of norfloxacin alone. When Maalox was given 2 h after norfloxacin, maximal concentrations of norfloxacin in plasma occurred between 1 and 1.5 h postdose, and absorption was reduced to a lesser extent, with a relative bioavailability of 81.31%. Norfloxacin concentrations in urine were also reduced as a result of antacid administration. Antacids containing aluminum and magnesium salts and calcium carbonate should be avoided by patients taking norfloxacin.

Absorption↗
PubMed1990

Multiple-dose pharmacokinetics and safety of oral amifloxacin in healthy volunteers.

The multiple-dose pharmacokinetics and safety of amifloxacin, a new fluoroquinolone antibacterial agent, were evaluated in healthy male volunteers. Amifloxacin was administered orally at 200, 400, or 600 mg every 12 h (q12h) and 400, 600, or 800 mg every 8 h (q8h) for 10 days. An additional dose was administered on day 11. Concentrations of amifloxacin in plasma and urine were measured on days 1, 5, and 11 by high-performance liquid chromatography. Steady-state amifloxacin concentrations were reached by day 5. Mean +/- standard deviation maximum observed amifloxacin concentrations in plasma were 2.52 +/- 1.12, 4.98 +/- 1.44, 5.40 +/- 2.02, 4.59 +/- 2.17, 6.53 +/- 2.44, and 8.01 +/- 3.00 micrograms/ml after the initial dose and 2.30 +/- 0.98, 5.41 +/- 0.74, 8.05 +/- 1.68, 6.87 +/- 2.81, 9.53 +/- 0.50, and 11.9 +/- 1.92 micrograms/ml on day 11 of the study for the 200-, 400-, and 600-mg q12h and 400-, 600-, and 800-mg q8h regimens, respectively. Amifloxacin was rapidly absorbed, as evidenced by the mean time to the maximum observed amifloxacin concentration of 0.98 h. Mean values for the terminal amifloxacin half-life in plasma ranged from 3.58 to 5.78 h. Mean amifloxacin concentrations in urine on day 11 in samples collected 0 to 2 h after dosing were 105, 417, 376, 336, 518, and 464 micrograms/ml for the 200-, 400-, and 600-mg q12h and 400-, 600-, and 800-mg q8h regimens, respectively. The mean amount of the dose excreted in the urine as amifloxacin was 53.9%. Amifloxacin was generally well tolerated, although there was a tendency for the subjects who received amifloxacin to experience more gastrointestinal, central nervous system, and cutaneous complaints than did those who received placebo. Clinically significant adverse reactions, including pruritus and transaminase elevations, occurred only at doses of 1,200 mg/day or above. Clinical and pharmacokinetic data suggest that orally administered amifloxacin may have utility in the treatment of urinary tract infections.

Administration, Oral↗
PubMed1990

In vitro selection of resistant Helicobacter pylori.

Four strains of Helicobacter pylori were subjected to an in vitro serial passage technique to compare the propensity of the organisms to develop resistance to seven classes of antibacterial agents. The passages were made on serially doubling concentrations of antibacterial agents incorporated into agar starting at one-half the base-line MIC. The frequency of spontaneous resistance was also determined for each strain at four and eight times the MIC of each antibacterial agent. Strains resistant to ciprofloxacin, metronidazole, erythromycin, and tobramycin were isolated. The experiments failed to select organisms resistant to bismuth subsalicylate, furazolidone, or amoxicillin, although the MIC of amoxicillin was increased 4- to 16-fold. With the exception of erythromycin, organisms with the selected resistance were stable after at least three passages on antibacterial agent-free medium. Spontaneous resistance rates were generally of a low magnitude and were not predictive of the serial passage results.

Anti-Bacterial Agents↗
PubMed1989

The effect of sucralfate pretreatment on the pharmacokinetics of ciprofloxacin.

Based on the results of our study of norfloxacin-sucralfate coadministration, we suspected that sucralfate would interact also with ciprofloxacin if the drugs were administered concurrently. Therefore, we decided to give a 1-g dose of sucralfate at 6 and 2 hours before a single 750-mg dose of ciprofloxacin and evaluate its effect on the bioavailability of ciprofloxacin. Twelve healthy, male volunteers received ciprofloxacin alone and with sucralfate pretreatment in a randomized, balanced, crossover design. Blood and urine samples were collected over 24 hours after ciprofloxacin administration, and drug concentrations were assayed by high-performance liquid chromatography. When sucralfate was given at 6 and 2 hours before ciprofloxacin, an average 30% decrease in ciprofloxacin's bioavailability was noted (p less than 0.05). Four of the 12 subjects, however, had decreases in the agent's area under the curve of more than 50% with sucralfate pretreatment. The results of this study suggest that ciprofloxacin and sucralfate should not be administered concurrently until a dosing interval is found that will avoid this potential interaction.

Adult↗
PubMed1989

Effects of aluminum and magnesium antacids and ranitidine on the absorption of ciprofloxacin.

The effect of an antacid (Maalox) and ranitidine administration on the absorption of ciprofloxacin was evaluated in healthy male volunteers who were enrolled in three separate studies. Each study was designed at a three- or four-period crossover and included the administration of 750 mg ciprofloxacin alone as a control treatment. Treatments that were evaluated included the administration of ciprofloxacin 5 to 10 minutes, 2 hours, 4 hours, and 6 hours after a single 30 ml dose of antacid; the administration of antacid 2 hours after ciprofloxacin was given; and the administration of ciprofloxacin 2 hours after a 200 mg ranitidine tablet. Administration of antacid within 4 hours before ciprofloxacin dose resulted in a significant decrease in ciprofloxacin absorption (p less than 0.05). Percentages of relative bioavailability compared with control values were 15.1%, 23.2%, and 70% for the 5 to 10 minute, 2 hour, and 4 hour antacid pretreatments, respectively. Administration of antacid 6 hours before or 2 hours after the ciprofloxacin dose did not affect absorption. Ranitidine did not alter ciprofloxacin absorption. Antacids that contain magnesium and aluminum salts may reduce the absorption of ciprofloxacin. The extent of this interaction appears to increase as the time between administration of the two drugs decreases. Ranitidine is suggested as an alternative to antacids for patients receiving treatment with ciprofloxacin.

Adult↗
PubMed1989

Sucralfate reduces the gastrointestinal absorption of norfloxacin.

The effect of sucralfate on the bioavailability of norfloxacin after single 400-mg doses of norfloxacin was evaluated in eight healthy males. Subjects received each of the following treatments in random sequence: (i), norfloxacin, 400 mg alone; (ii) sucralfate, 1 g, concurrently with norfloxacin, 400 mg; and (iii) sucralfate, 1 g, followed by norfloxacin, 400 mg, 2 h later. One day before administration of treatments 2 and 3, 1 g of sucralfate was given at 7 a.m., 11 a.m., 5 p.m., and 10 p.m. Blood samples were collected immediately before the norfloxacin dose and at 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 12, and 24 h postdose. Urine was collected in divided intervals: from 0 to 12, from 12 to 24, and from 24 to 48 h. Norfloxacin concentrations in plasma and urine were determined by high-performance liquid chromatography. Mean area under the plasma concentration-versus-time curve extrapolated to infinity decreased significantly (P less than 0.001) after norfloxacin was given with and 2 h after sucralfate. The relative bioavailabilities were 1.8% when norfloxacin was taken with sucralfate and 56.6% when it was taken 2 h after sucralfate. After norfloxacin was given alone, the mean norfloxacin concentrations in urine collected during intervals of 0 to 12, 12 to 24, and 24 to 28 h were 118.9 +/- 72.3, 18.8 +/- 12.5, and 2.4 +/- 2.2 micrograms/ml, respectively. After norfloxacin was given with sucralfate, however, the mean norfloxacin concentrations in urine collected during the same time intervals were 6.8 +/- 4.7, 1.8 +/- 1.4, and 0 +/- 0 microgram/ml, respectively. Because of low pH and relatively high magnesium concentration in urine, susceptibilities of bacteria in urine are 8- to 32-fold lower than in broth. This fact, in combination with the reduced bioavailability of norfloxacin in the presence of sucralfate or antacids, is likely to result in treatment failure. The effect of sucralfate given after norfloxacin was not examined, nor was the effect of sucralfate given more than 2 h before norfloxacin. Administration or norfloxacin with sucralfate should therefore by avoided.

Administration, Oral↗
PubMed1989

Effect of oral antacid administration on the pharmacokinetics of intravenous doxycycline.

The effect of oral antacid administration on the pharmacokinetics of intravenous doxycycline was studied. In a randomized crossover design, six healthy male volunteers received an infusion of 200 mg of doxycycline hyclate on two occasions separated by 7 days. On one occasion, subjects were given 30 ml of aluminum hydroxide orally four times a day for 4 days, beginning 2 days prior to doxycycline dosing. Blood and urine samples were collected up to 48 and 96 h after the infusion, respectively, and were analyzed by a microbial assay. Values for volume of distribution at steady state, nonrenal clearance, urine recovery, and urine pH were not statistically different among treatment groups. With concomitant antacid therapy, the half-life of intravenous doxycycline was shortened from 16.2 +/- 2.6 to 11.2 +/- 1.2 h (P = 0.003), and total body clearance increased from 37.4 +/- 6.5 to 54.1 +/- 12.3 ml/min (P = 0.008). Area under the concentration-time curve for serum was decreased by 18 to 44%, with a 22 to 41% increase in renal clearance. Although the increase in nonrenal clearance ranged from 11 to 128%, the high variability led to a nonsignificant difference (P = 0.07). Concomitant oral antacid therapy may significantly enhance the clearance of intravenous doxycycline.

Adolescent↗
PubMed1989

Effect of lomefloxacin on theophylline pharmacokinetics.

A study involving 25 health male volunteers was conducted to evaluate the effect of lomefloxacin on the pharmacokinetics of theophylline. The mean age was 22.4 +/- 3.0 years, and the mean weight was 77.3 +/- 7.7 kg. A single 6-mg/kg aminophylline dose was given intravenously on study days 1 and 15. The subjects received a 400-mg lomefloxacin dose (four 100-mg capsules) on study days 9 through 15. No treatment was given on study days 2 through 8. Thirteen blood samples were collected within 24 h after each aminophylline dose. Theophylline concentrations in serum were measured by enzyme immunoassay (EMIT). The mean aminophylline dose was 437 +/- 36 mg, equivalent to 344 mg of theophylline. Multiple doses of lomefloxacin had no effect on the area under the concentration-time curve from 0 h to infinity, maximal concentration, or clearance of theophylline from serum. There was a slight increase in the theophylline half-life from 6.72 +/- 1.63 to 7.02 +/- 1.37 h after lomefloxacin dosing (P = 0.04); however, the change was clinically insignificant. No change in theophylline dose is required when lomefloxacin therapy is instituted in a patient receiving theophylline.

4-Quinolones↗
PubMed1989

Evaluation of intravenous ciprofloxacin in patients with nosocomial lower respiratory tract infections. Impact of plasma concentrations, organism, minimum inhibitory concentration, and clinical condition on bacterial eradication.

Fifty patients with gram-negative lower respiratory tract infections were treated with intravenous ciprofloxacin to evaluate efficacy and safety. Relationships between individual pharmacokinetics and clinical and bacteriologic outcome were studied. Ciprofloxacin concentrations in plasma were determined by high-performance liquid chromatography. Respiratory secretion cultures were obtained daily to determine the eradication day of the infecting organism. Susceptibility (minimum inhibitory concentration) to ciprofloxacin and other antimicrobials was determined using standard microdilution techniques. The mean age of the patients was 70 years. They had multiple underlying diseases, and two thirds of them were ventilator dependent at entry. Approximately 50% of the patients had failed previous treatment for the same infections. Patients infected with Enterobacteriaceae or Haemophilus influenzae with minimum inhibitory concentrations of less than 0.25 mg/L responded well to intravenous ciprofloxacin therapy (200 mg every 12 hours). The organisms were eradicated from sputum cultures usually within 1 day after ciprofloxacin therapy was started. Most clinical failures occurred in patients who were infected with Pseudomonas aeruginosa and had multiple underlying diseases. Pseudomonas aeruginosa was isolated from 10 patients with pneumonia, 2 patients with lung abscess, and 1 patient with bronchiectasis. The Pseudomonas isolate acquired resistance during ciprofloxacin treatment in 7 patients with pneumonia and in all of the remaining 3 patients. We conclude that ciprofloxacin is safe and effective at a dosage of 200 mg administered intravenously every 12 hours for nosocomial lower respiratory tract infections caused by Enterobacteriaceae or Haemophilus species. Many patients who had failed previous antibiotic treatment for Enterobacteriaceae infections had good clinical response to ciprofloxacin therapy. Studies using either higher dosages of ciprofloxacin or combination therapy should be conducted to determine if acquired resistance can be avoided in Pseudomonas infections.

Aged↗
PubMed1988

The effect of renal impairment and haemodialysis on single dose pharmacokinetics of oral enoxacin.

The effect of renal impairment on the single dose pharmacokinetics of oral enoxacin was studied in 28 volunteers with creatinine clearances ranging from less than 15 to 120 ml/min, including patients undergoing chronic haemodialysis. Following an overnight fast, 400 mg of enoxacin was administered orally to each subject. Blood and urine samples were collected at predetermined times for 48 and 72 h, respectively. Plasma and urine samples were assayed for enoxacin and for oxo metabolite concentrations by a specific high performance liquid chromatographic method. Area under the concentration-time curve from time 0 to infinity (AUC0-infinity) was increased in subjects with renal impairment. Plasma half-life (10.6-11.6 h) in volunteers with severe renal impairment was approximately double the 5.2 h half-life found in subjects with normal renal function, and this should result in steady-state enoxacin concentrations approximately double those measured in normal subjects given equivalent doses. Haemodialysis did not remove significant amounts of enoxacin. A significant correlation between creatinine clearance and enoxacin renal clearance was observed (r = 0.97).

Administration, Oral↗