Biomedical subjects

J J Schentag

Publications and source records attributed to J J Schentag.

At least 109 records · Page 6Linked to original sources

PubMed1990

Comparative evaluation of the pharmacokinetics of N-methylthiotetrazole following administration of cefoperazone, cefotetan, and cefmetazole.

The comparative pharmacokinetics and in vivo production of N-methylthiotetrazole (NMTT) were evaluated following administration of cefoperazone, cefotetan, and cefmetazole. In a randomized-crossover manner, 11 healthy male volunteers received single 2-g intravenous doses of each agent and serial blood and urine samples were collected. Concentrations of NMTT and the parent compound in plasma, urine, and the reconstituted antibiotic solution were determined by high-pressure liquid chromatography. The amounts of NMTT administered were 6.06 +/- 0.46, 14.4 +/- 0.87, and 17.4 +/- 1.06 mg for cefoperazone, cefotetan, and cefmetazole, respectively (P less than 0.05). The mean NMTT plasma concentration-time profiles following administration of each cephalosporin were markedly different. Six hours after dosing, NMTT concentrations in plasma following cefoperazone administration were higher than those following administration of cefmetazole and cefotetan. Urinary recoveries of NMTT averaged 137.0 +/- 37.1, 38.3 +/- 6.98, and 25.2 +/- 5.95 mg following administration of cefoperazone, cefotetan, and cefmetazole, respectively (P less than 0.01). The apparent amount of NMTT produced in vivo, calculated by subtracting the amount of NMTT administered from the amount of NMTT excreted in urine, was significantly lower following cefmetazole administration than after administration of cefoperazone and cefotetan (P less than 0.01). The discrepancy between in vitro NMTT production (cefmetazole greater than cefotetan greater than cefoperazone) and the amount of NMTT formed in vivo and excreted unchanged (cefoperazone greater than cefotetan greater than cefmetazole) suggests that in vivo production of NMTT is dependent on the disposition of the parent cephalosporin. These results further suggest that cephalosporins which undergo extensive biliary excretion, such as cefoperazone, are associated with the greatest amount of in vivo NMTT release, whereas cephalosporins which are primarily renally excreted, such as cefmetazole, are associated with the lowest in vivo production of NMTT.

Adult↗

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↗

PubMed1990

Lack of effect of piroxicam on theophylline clearance in healthy volunteers.

This study was conducted to determine if piroxicam alters the clearance or metabolism of theophylline in healthy adults. Six male volunteers were given aminophylline 6 mg/kg iv before and after piroxicam treatment. Piroxicam 20 mg/d po was administered for seven days. Serum samples were collected before and for 24 hours after each aminophylline dose. Theophylline serum concentrations were determined using the Abbott TDx automated immunoassay system. Theophylline and its 1,3-dimethyluric acid metabolite were measured in 24-hour urine collections. Serum theophylline concentration versus time curves were plotted and pharmacokinetic parameters determined for each subject. None of the derived parameters differed as a result of piroxicam exposure. Theophylline metabolites, clearance, half-life, and volume of distribution were compared during the baseline and piroxicam phases and were found to be similar. It was concluded that piroxicam does not alter the clearance, distribution, volume, or metabolism of theophylline in healthy adult volunteers.

Adult↗

PubMed1990

P&T Committee review of fluconazole: an effective alternative to antifungal therapy.

Fluconazole is a new antifungal agent available in both oral and parenteral formulations. According to the experts in this roundtable discussion, fluconazole represents a major clinical advance in the treatment of candidiasis and cryptococcosis in cancer patients, patients with AIDS, organ transplant recipients, and other patients at risk for opportunistic mycoses. The pharmacokinetic profile for fluconazole permits infrequent dosing and also makes it ideal for tissue site infections. Fluconazole's low toxicity gives it an advantage over currently available antifungal therapy and will permit prompt presumptive treatment of selected infections.

Antifungal Agents↗

PubMed1990

Correlation of pharmacokinetic parameters to efficacy of antibiotics: relationships between serum concentrations, MIC values, and bacterial eradication in patients with gram-negative pneumonia.

In vitro, antibiotics are known to kill bacteria in predictable relationships to their broth concentrations. It was our hypothesis that serum concentration was an important determinant of the rate of bacterial eradication in patients. This contention was reinforced by animal studies, which have clearly demonstrated concentration-related antibacterial activity. The animal models rely on reduction of bacterial colony counts as an endpoint of effect, and demonstrate that colony count reductions are related to antibiotic dose and probably to serum concentration. We adapted these methods for use in intubated patients with Gram-negative pneumonia. Briefly, each patient had extensive staging of the pneumonic process, and the Gram-negative organism was isolated and its minimal inhibitory concentration (MIC) was determined. In each patient measurement of the antibiotic serum concentrations in the interval between two doses of the drug was also performed. The pharmacokinetic profile of the drug was then superimposed on the bacterial MIC, and we then derived the patients individual peak to MIC ratio, area above MIC, and time above MIC. Each of these pharmacokinetic parameters was then related to the time required to eradicate the bacterial pathogens in the patient. For beta-lactams and quinolones, time above MIC was the most predictive of bacterial eradication times. Clearly, these methods can be used to develop dosing strategies for patients, as well as to determine clinically relevant doses and dosing strategies in clinical trials. Further work is needed, however, to assess whether these concepts hold for other types of bacteria (such as Gram-positive) or apply as accurately to other infection sites in addition to pneumonia.

Aged↗

PubMed1989

Prospective surveillance of antibiotic-associated coagulopathy in 970 patients.

N-methyl-thio-tetrazole (NMTT) has been proposed as a causative factor in antibiotic-associated coagulopathy. To evaluate this hypothesis, a nationwide surveillance program was initiated to determine the relative frequency of antibiotic-associated coagulopathy and the importance of specific risk factors. A total of 970 patients were studied, with 491 being treated for infections and 479 receiving antimicrobial surgical prophylaxis. The NMTT-containing antibiotic cefotetan was compared with non-NMTT-containing antibiotics, for example, cefoxitin and cefazolin (prophylaxis only), and an aminoglycoside-antianaerobic (AG + AA) combination. Prothrombin time (PT) and partial thromboplastin time (PTT) were measured for each patient prior to the start of antibiotics and within 24-96 hours after the conclusion of drug administration. The patient population was relatively young [mean (SD) age 51.0 (20) yrs] with good nutritional status. The overall frequency of hypoprothrombinemia (4.5%) and bleeding (1.7%) was very low, and was highest with the use of AG + AA (p less than 0.05). No statistical differences were observed for the remaining antibiotic regimens in either the prophylaxis or treatment group. Logistic regression analysis identified treatment with the AG + AA combination, presence of liver disease, and renal dysfunction as factors associated with an increased risk of hypoprothrombinemia. In conclusion, this study suggests that the frequency of antibiotic-associated coagulopathy is low, regardless of antibiotic, in patients who are not critically ill and not malnourished.

Adolescent↗

PubMed1989

Effects of enteral and intravenous antimicrobial treatment on survival following intestinal ischemia in rats.

One hundred and twenty rats underwent transection of the superior mesenteric artery. The animals were randomly divided into eight groups of 15 animals. Control group 1 and groups 3, 5, and 7 received intravenous normal saline, gentamicin, metronidazole, and gentamicin plus metronidazole, respectively. Control group 2 and groups 4, 6, and 8 received the same compounds enterally. Small and large bowel sections were taken postmortem and a necrosis score was assigned in blinded fashion. Gentamicin did not prolong survival, indicating that gram-negative microbes were not important in this pathology. Longer survival times for animals given either metronidazole or gentamicin plus metronidazole (P less than 0.01) indicate that anaerobes were a causative factor in mortality. During the first 15 hr after ischemia, antibiotics did not change mortality. After 15 hr, enteral administration was superior to intravenous administration in any regimen including metronidazole (P less than 0.01).

Animals↗

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

Single-dose cefmetazole versus multiple dose cefoxitin for prophylaxis in abdominal surgery.

One hundred and ninety-five patients undergoing abdominal surgical procedures completed a multicentre, randomized, open-label study comparing the safety and efficacy of cefmetazole and cefoxitin for the prevention of postoperative wound infection. Cefmetazole was administered iv in a single 2 g dose given within 90 min of the operation. Cefoxitin was administered in a single 2 g, similarly timed, preoperative dose and two additional doses given at 6 h intervals after surgery. For operations that exceeded 2-4 h duration an additional dose of each agent was administered. Patients undergoing colorectal operations received oral neomycin and erythromycin as bowel preparation. Colorectal operations were performed most frequently (49% of patients) followed by cholecystectomies (26%) and gastroduodenal procedures (21%). The operative site infection rate was 6.5% for cefmetazole and 7.7% for cefoxitin (P greater than 0.05). Serious drug related adverse effects were not observed. This study demonstrates that administration of single-dose cefmetazole is as effective as a standard three dose regimen of cefoxitin for prophylaxis with abdominal operations.

Abdomen↗

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

Inhibition of enoxacin absorption by antacids or ranitidine.

Ten normal volunteers participated in a randomized, five-way crossover study to determine the effect of concurrent enoxacin and antacid or ranitidine administration on enoxacin absorption. The bioavailability of a single oral 400-mg enoxacin dose was significantly decreased, by 73 and 49%, when Maalox TC was administered 0.5 and 2 h before enoxacin, respectively. Enoxacin bioavailability was not significantly altered when the antacid was given 8 h before or 2 h after enoxacin administration. Ranitidine, administered intravenously 2 h before enoxacin, also significantly decreased enoxacin bioavailability, by 40%. The correlation between the proximity of antacid administration and the magnitude of the decrease in enoxacin bioavailability supports complexation as the mechanism of the antacid-enoxacin interaction. However, reduction of enoxacin bioavailability by ranitidine suggests that elevated gastric pH may also play a role in the antacid-enoxacin drug-drug interaction.

Adolescent↗

PubMed1989

Comparison of N-methylthiotetrazole dispositions in healthy volunteers following single intravenous doses of moxalactam, cefoperazone, and cefotetan.

The N-methylthiotetrazole side chain (NMTT) that is present on several cephalosporins has been implicated in the development of antibiotic-associated hypoprothrombinemia. A randomized three-way crossover trial was conducted to compare the release of the NMTT side chain from three NMTT-containing antibiotics. Single 2-g doses of moxalactam, cefoperazone, and cefotetan were given, followed by serial blood and urine sampling. The concentrations of the parent compound and the NMTT side chain in plasma, urine, and the reconstituted antibiotic solution were determined by high-pressure liquid chromatography. Peak NMTT concentrations ranged from 0.42 to 16.50 micrograms/ml and were significantly higher after moxalactam administration than after cefoperazone or cefotetan administration (P less than 0.01). The NMTT trough concentrations (12.5 h) ranged from nondetectable to 2.47 micrograms/ml and tended to be greater following cefoperazone administration. The amounts of NMTT administered (e.g., the amount in the reconstituted antibiotic solution) were 25.8 +/- 1.4, 15.2 +/- 0.9, and 22.1 +/- 3.0 mg following moxalactam, cefoperazone, and cefotetan administration, respectively (P less than 0.01). In contrast, urinary recoveries of NMTT were 57.4 +/- 26.2, 73.6 +/- 44.3, and 29.7 +/- 22.9 mg following moxalactam, cefoperazone, and cefotetan, respectively. The amount of NMTT formed in vivo and excreted unchanged, as assessed by subtracting in vitro NMTT formation from NMTT urinary recovery, was significantly higher after cefoperazone than after moxalactam or cefotetan administration (P less than 0.05). The discrepancy between in vitro NMTT production (moxalactam > cefotetan > cefoperazone) and the amount of NMTT formed in vivo and excreted unchanged (cefoperazone > moxalactam > cefotetan) demonstrated that the in vivo production of NMTT is dependent on the disposition of the parent cephalosporin.

Adult↗

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

Pharmacokinetics of ampicillin (2.0 grams) and sulbactam (1.0 gram) coadministered to subjects with normal and abnormal renal function and with end-stage renal disease on hemodialysis.

The single-dose pharmacokinetics of intravenously administered ampicillin (2.0 g) and sulbactam (1.0 g) were studied in normal subjects and in patients with various degrees of creatinine clearance (CLCR). Six normal subjects (CLCR, greater than 60 ml/min), six patients with mild renal failure (CLCR, 31 to 60 ml/min), four patients with severe renal failure (CLCR, 7 to 30 ml/min), and four patients requiring maintenance hemodialysis (CLCR, less than 7 ml/min) were studied. The terminal half-lives for ampicillin and sulbactam more than doubled in patients with severe renal failure compared with subjects with normal renal function and mild renal insufficiency. CLCR significantly correlated with ampicillin (r = 0.88) and sulbactam (r = 0.54) total body clearance. Mean steady-state volume of distribution and nonrenal clearance for ampicillin and sulbactam were not affected by renal function. Hemodialysis approximately doubled the ampicillin and sulbactam total body clearance. Mean totals of 34.8 +/- 4.0% of the ampicillin dose and 44.7 +/- 3.2% of the sulbactam dose were removed during a 4-h hemodialysis treatment. A slight rebound in concentrations in serum after hemodialysis was observed for both drugs in all four subjects. In hemodialysis patients, the ampicillin half-life was 17.4 +/- 8.0 h and the sulbactam half-life was 13.4 +/- 7.4 h. The ampicillin and sulbactam half-lives were appreciably altered during the hemodialysis period (means of 2.2 and 2.3 h, respectively). The nearly parallel decrease in total body clearance, with volume of distribution and nonrenal clearance remaining relatively constant, suggests that the same ratio of ampicillin to sulbactam is appropriate regardless of renal function. An adjustment of the ampicillin (2.0 g) and sulbactam (1.0 g) dose to twice daily would be appropriate in patients with a CLCR between 7 and 30 ml/min. Doses should be given every 24 h for those undergoing maintenance hemodialysis. On hemodialysis days, doses should be given after hemodialysis.

Adult↗

PubMed1989

A clinical pharmacy-oriented drug surveillance network: results of a nationwide antibiotic utilization review of bacterial pneumonia--1987.

One hundred eighteen pharmacists enrolled in the Drug Surveillance Network completed a survey of antibiotic prescribing patterns for bacterial infections. A total of 319 hospitalized patients being treated for suspected or documented bacterial pneumonia were monitored, and this paper summarizes the data collected on this specific subpopulation. Two hundred three patients (64 percent) were treated for community-acquired pneumonia and 116 patients (36 percent) were treated for nosocomial pneumonia. Seventy-three percent of the nosocomial pneumonias were culture-positive, with a gram-negative microorganism as the predominant isolate. Forty-eight percent of the community-acquired pneumonias were culture-positive with a mixture of gram-positive and gram-negative organisms. Fifty percent of patients were treated with a single agent, 33 percent with two antibiotics, and the remaining 17 percent with a combination of three or more antibiotics. A satisfactory response was noted for 62 and 76 percent of the patients with nosocomial and community-acquired pneumonias, respectively. Twenty percent of the pneumonia patients were switched to oral drug after an average of five days of therapy and discharged from the hospital. Twenty-five adverse events that were possibly or probably related to the antibiotic regimen were reported in 23 of the 350 patients for an overall incidence of 6.5 percent. The results of this survey provide a cross-sectional view of antibiotic prescribing patterns for the treatment of bacterial pneumonia and the outcome of therapy under actual clinical conditions of use.

Adolescent↗

PubMed1989

Safety and acid-suppressant properties of histamine2-receptor antagonists for the prevention of stress-related mucosal damage in critical care patients.

Therapeutic intervention for the prevention of stress-related mucosal damage (SRMD) is currently directed at decreasing mucosal exposure to endogenous hydrochloric acid. We conducted a double-blind, parallel-group study in critically ill patients to investigate the comparative safety and acid-suppressant properties of the intravenously administered H2-receptor antagonists cimetidine and famotidine. This is a preliminary analysis. Study patients received either famotidine 20 mg q12h or cimetidine 300 mg q6h or q12h. Cimetidine dosing intervals were based upon the degree of renal and hepatic dysfunction due to pharmacokinetic considerations. In critically ill patients with severe renal impairment, a pH of greater than or equal to 4.0 was maintained more consistently with famotidine 20 mg q12h compared with treatment with cimetidine. In terms of safety, a greater number of patients receiving cimetidine reported adverse clinical experiences than those receiving famotidine and a greater number of cimetidine patients had to be withdrawn from the study when compared with famotidine patients. In conclusion, preliminary results of this study suggest that famotidine has superior acid-suppressant properties and a better safety profile when used intravenously for the prevention of SRMD in critically ill patients.

Adult↗