Clinical pharmacy and clinical research.
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History of Pharmacy↗
Biomedical subjects
J A Bosso
Publications and source records attributed to J A Bosso.
Compatibility and stability of cefazolin sodium, clindamycin phosphate, and gentamicin sulfate in two intravenous solutions.
We studied the compatibility and stability of clindamycin phosphate admixed with gentamicin sulfate and cefazolin sodium in small-volume diluents under specific storage conditions. In two replicate 100 ml dilutions of NaCl 0.9% injection and dextrose 5% (D5W) injection, clindamycin phosphate 900 mg was admixed with gentamicin sulfate 80 mg and cefazolin sodium 1 g. Drug concentrations were determined at the time of preparation and at 1, 4, 8, 12, 24, and 48 hours. Clindamycin and cefazolin were assayed by high-performance liquid chromatography and gentamicin was assayed by fluorescence polarization immunoassay. Visual inspections and pH determinations of each solution were performed at each assay time. Test solutions were maintained at constant room temperature and fluorescent lighting. Concentrations of clindamycin and gentamicin remained greater than 90 percent of the original concentrations throughout the study. Cefazolin concentrations dropped below 90 percent in D5W injection at 4 hours after admixture and at 12 hours after admixture in NaCl 0.9% injection. Visual analyses and pH changes revealed no significant changes. The combination of clindamycin phosphate 900 mg, gentamicin sulfate 80 mg, and cefazolin sodium 1 g in D5W 100 ml was found to be compatible for up to 4 hours. The duration of compatibility for these three drugs in 100 ml of NaCl 0.9% was 12 hours.
Cefazolin↗
Lack of correlation between objective indicators and clinical-response scores during antimicrobial therapy for acute pulmonary exacerbations of cystic fibrosis.
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Anti-Bacterial Agents↗
In vitro inactivation of aminoglycosides by cephalosporin antibiotics.
The in vitro inactivation of aminoglycoside antibiotics by semisynthetic penicillins complicates antibiotic assays. Due to the increasing number of new cephalosporins and use of aminoglycoside-cephalosporin combinations, we determined the in vitro stability of 28 aminoglycoside-cephalosporin combinations (gentamicin sulfate, tobramycin sulfate, netilmicin sulfate [10 micrograms/mL], and amikacin [20 micrograms/mL] in combination with cefazolin sodium, cefoxitin sodium, cefoperazone sodium, cefotaxime sodium, ceftazidime acid pentahydrate, cefsulodin sodium, or cefpiramide sodium at 100, 200, and 300 micrograms/mL). These mixtures were incubated at 37 degrees C and sampled at 0, 8, and 24 hours. Amikacin and tobramycin were most stable and netilmicin was the least stable of the aminoglycosides. Cefoxitin, ceftazidime, and cefotaxime were the least inactivating of the cephalosporins. When combined with first- and second-generation cephalosporins, aminoglycosides are relatively stable, but some laboratory precautions may be necessary when determining aminoglycoside levels in the presence of third-generation cephalosporin compounds.
Aminoglycosides↗
Ciprofloxacin versus tobramycin plus azlocillin in pulmonary exacerbations in adult patients with cystic fibrosis.
Twenty adult patients with cystic fibrosis who were experiencing acute pulmonary exacerbations were enrolled in a randomized, controlled trial comparing oral ciprofloxacin with intravenous tobramycin plus azlocillin. Efficacy of the two treatments was compared based upon changes in clinical status, pulmonary function tests, white blood cell counts, and quantitative bacteriology of sputum. No statistically significant differences were detected in these parameters of response between the two treatment groups (p greater than 0.05). Ciprofloxacin appears to be therapeutically equivalent to intravenous antibiotics in the treatment of adult patients with cystic fibrosis who are experiencing pulmonary exacerbations associated with susceptible bacteria.
Adult↗
Absence of rapidly developing resistance during treatment of cystic fibrosis patients with aztreonam.
The in vitro activity of aztreonam and 10 other antibiotics was determined for clinical isolates of Pseudomonas aeruginosa from 18 cystic fibrosis patients obtained before, at the end of, and 7-14 days after the completion of therapy with aztreonam. The percent of isolates susceptible to aztreonam at each sampling period were 79%, 78%, and 81% respectively.
Anti-Bacterial Agents↗
Efficacy of aztreonam in pulmonary exacerbations of cystic fibrosis.
A noncomparative pilot study was conducted to assess the potential usefulness of aztreonam in pulmonary exacerbations of cystic fibrosis. Of 27 patients initially enrolled 25 received sufficient courses of aztreonam therapy to be evaluable. All patients received 200 mg/kg/day of aztreonam in 4 equally divided doses administered intravenously. Of 57 isolates of Pseudomonas aeruginosa from pretherapy sputum cultures, 48 were susceptible to aztreonam in vitro as were 11 of 18 strains isolated at the conclusion of therapy. With treatment colony counts of P. aeruginosa in sputum were reduced by 3 log10 or more in 15 patients. It was totally (but temporarily) eradicated in 11 of these patients. Clinical scores and white blood cell counts improved significantly (P less than 0.05). Side effects of aztreonam were limited to transient elevations of liver enzymes occurring in 16 patients. Aztreonam merits further evaluation in a randomized, comparative trial with standard antibiotic therapy for cystic fibrosis.
Adolescent↗
In vitro activity of aztreonam combined with tobramycin and gentamicin against clinical isolates of Pseudomonas aeruginosa and Pseudomonas cepacia from patients with cystic fibrosis.
The in vitro activity of aztreonam combined with tobramycin and with gentamicin was assessed in 78 clinical isolates of Pseudomonas aeruginosa and 11 clinical isolates of Pseudomonas cepacia from patients with cystic fibrosis. Synergy was detected in 56.4% of P. aeruginosa isolates and 60% of P. cepacia isolates with the aztreonam-tobramycin combination and in 49.3% of P. aeruginosa isolates and 81.8% of P. cepacia isolates with the aztreonam-gentamicin combination. No antagonism was observed. These combinations merit clinical evaluation in the treatment of patients with cystic fibrosis.
Aztreonam↗
Compatibility and stability of clindamycin phosphate-aminoglycoside combinations within polypropylene syringes.
The stability and compatibility of clindamycin phosphate admixed separately with gentamicin sulfate, tobramycin sulfate, and amikacin sulfate in polypropylene syringes under specific storage conditions were studied. In duplicate syringes, clindamycin phosphate 900 mg was admixed with sterile NaCl 0.9% l ml and with either gentamicin sulfate 120 mg, tobramycin sulfate 120 mg, or amikacin sulfate 750 mg. In duplicate polypropylene syringes, control solutions of clindamycin phosphate and each aminoglycoside were prepared separately and stored under the same conditions. The clindamycin control consisted of clindamycin phosphate 900 mg in 6 ml. The gentamicin and tobramycin controls consisted of gentamicin sulfate and tobramycin sulfate 120 mg in 3 ml plus 1 ml of sterile NaCl 0.9%. The amikacin control consisted of amikacin sulfate 750 mg in 3 ml plus 1 ml of sterile NaCl 0.9%. Drug concentrations were determined at the time of preparation and 1, 4, 8, 12, 24, and 48 hours thereafter. Aminoglycosides were assayed by fluorescence polarization immunoassay and clindamycin was assayed by high performance liquid chromatography. Visual inspections and pH determinations of each combination and control solution were performed at each assay time. For the clindamycin, gentamicin, tobramycin, and amikacin control solutions, changes in concentration were within ten percent of the original concentration. Concentrations of clindamycin and gentamicin when admixed together also remained within ten percent of the original concentration. Similar results were found with concentrations of clindamycin and amikacin when admixed together. Tobramycin and clindamycin formed a lasting precipitate upon initial contact when admixed under the study conditions.
Amikacin↗
Comment: Employment as a bias.
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Drug Industry↗
Intrapatient variation in aminoglycoside disposition in cystic fibrosis.
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Adolescent↗
A placebo-controlled trial of topical 8% arildone cream early in recurrent genital herpes.
Arildone is an aryl diketone which is inhibitory in vitro against herpes simplex virus type 2 at a concentration of 2 micrograms/ml or less. One hundred forty-five patients with recurrent genital herpes were enrolled in a multicenter, randomized, placebo-controlled, double-blind trial to evaluate the efficacy and safety of an 8% arildone cream. Patients initiated therapy a mean of 9.9 h and a maximum of 24 h after the reported onset of lesions and applied medication 6 times daily for 7 days. The duration of viral shedding was shorter among women (P less than 0.05) and the duration of local itching was shorter among men (P less than 0.05) in patients that received arildone than in those that received placebo, but there were no significant differences between treatment groups in duration of pain, time to crusting or healing of lesions, or percentage of patients developing new lesions. Mild local irritation after application of ointment was common and occurred equally in both treatment groups. Despite early application, topical arildone cream was ineffective in the therapy of acute recurrences of genital herpes.
Administration, Topical↗
Norfloxacin: a quinoline antibiotic.
Norfloxacin is a quinoline (quinolinecarboxylic acid) that should prove successful in treating infections that currently require hospitalization and intravenous antibiotics. Although a nalidixic acid derivative, it possesses greater antibacterial activity against gram-positive and gram-negative bacteria. Compared with other antimicrobial agents, norfloxacin is more potent than the aminoglycosides, first-, second-, and third-generation cephalosporins, tetracycline, trimethoprim-sulfamethoxazole, carbenicillin, piperacillin, nalidixic acid, oxolinic acid, cinoxacin, and enoxacin. In the clinical studies to date, the side effects of norfloxacin have been minimal, but include nausea, vomiting, anorexia, dizziness, headache, drowsiness, depression, and a bitter taste in the mouth. In studies with more than 4000 patients, the incidence of side effects ranged from 3.9 to 4.7 percent, with most appearing by the second day of therapy.
Animals↗
Compatibility of clindamycin phosphate with amikacin sulfate at room temperature and with gentamicin sulfate and tobramycin sulfate under frozen conditions.
The stability and compatibility of clindamycin phosphate with three aminoglycosides, amikacin sulfate, tobramycin sulfate, and gentamicin sulfate, admixed in either glass bottles or plastic bags, were studied under various storage conditions. In addition to the various two-drug combinations, each antibiotic was studied alone in the same solutions under the same storage conditions investigated for the various combinations. Clindamycin phosphate was admixed with amikacin sulfate in 100 ml glass bottles of both dextrose 5% in water (D5W) and NaCl 0.9%. The resultant solutions were examined for visual clarity; both pH and antibiotic concentrations were measured at the time of mixing and at 1, 4, 8, 12, 24, and 48 hours later. The solutions were maintained at room temperature under ambient lighting conditions throughout the observation period. Clindamycin phosphate was also admixed with tobramycin sulfate and gentamicin sulfate, in separate experiments, in 50 ml plastic bags of D5W and NaCl 0.9%. These solutions were examined, at the time of mixing, for visual clarity, pH, and antibiotic concentration and then frozen at -20 degrees C. They were thawed 14 and 28 days later and reexamined. Clindamycin phosphate concentrations were measured by high performance liquid chromatography; those of the aminoglycosides were determined by a fluorescence polarization immunoassay. A working definition of significant instability or incompatibility was defined as a greater than 10 percent loss of original antibiotic concentration. All single antibiotic solutions were stable throughout the observation periods.(ABSTRACT TRUNCATED AT 250 WORDS)
Amikacin↗
Stability of clindamycin phosphate with aztreonam, ceftazidime sodium, ceftriaxone sodium, or piperacillin sodium in two intravenous solutions.
In admixtures containing clindamycin and either aztreonam, ceftazidime, ceftriaxone, or piperacillin in either 5% dextrose injection (D5W) or 0.9% sodium chloride injection (NS), the stability of each drug was studied. Each of the following combinations of drugs was added to 100-mL glass bottles of base solution: clindamycin phosphate 0.9 g and aztreonam 2.0 g, clindamycin phosphate 0.9 g and ceftazidime sodium 2.0 g, clindamycin phosphate 1.2 g and ceftriaxone sodium 2.0 g, and clindamycin phosphate 0.9 g and piperacillin sodium 4.0 g. Duplicate samples were prepared. Admixtures containing each single drug were also tested. Samples were visually inspected and tested for pH and drug concentration immediately after mixing and at 1, 4, 8, 12, 24, and 48 hours of storage in room temperature and light. Drug concentrations were determined by high-performance liquid chromatographic assay methods. Ceftriaxone retained greater than 90% of its original concentration for 24 hours in single-drug admixtures in NS, for eight hours with clindamycin in NS, and for one hour with clindamycin in D5W. Ceftazidime retained greater than 90% potency for 24 hours with clindamycin in D5W. In all other test admixtures, all drugs were stable for 48 hours. Under the conditions studied, clindamycin is compatible in the admixtures tested with aztreonam and piperacillin. Admixtures of clindamycin and ceftazidime in D5W should be used within 24 hours at room temperature. Clindamycin and ceftriaxone can be mixed in NS if administered within eight hours, but ceftriaxone is stable for only one hour in combination with clindamycin in D5W.
Aztreonam↗
Tolerance and percutaneous absorption of topically applied arildone.
Arildone, an investigational antiviral agent, was compared to both its vanishing cream and 90% dimethyl sulfoxide (DMSO) solution vehicles to determine cutaneous and systemic tolerance as well as percutaneous absorption. In separate studies, immunosuppressed patients randomly received either arildone in vanishing cream (study 1), arildone in DMSO solution (study 2), or the vehicles without arildone. Test formulations were applied to the same area of one forearm four times daily for seven days. Blood, urine, and fecal samples were collected on days 1, 4, and 7, and patients were observed daily. Arildone was sporadically detected in biologic specimens suggesting limited percutaneous absorption. Unexpectedly, DMSO did not appear to enhance absorption of the drug. No clinical or laboratory evidence of systemic intolerance was observed for any preparation. While cutaneous tolerance was excellent for the vanishing cream preparations, the DMSO preparations were associated with a high (90%) incidence of erythematous reactions.
Administration, Topical↗
Effect of probenecid on the formation and elimination of acyl glucuronides: studies with zomepirac.
When 100 mg oral zomepirac was taken with 500 mg b.i.d. oral probenecid by six healthy subjects, the disposition of zomepirac was markedly altered. Probenecid decreased total plasma clearance of zomepirac by 64%, which resulted in an increase in bioavailability from 0.55 without probenecid to 0.84 when given concurrently. The apparent metabolic clearance of zomepirac to form zomepirac acyl glucuronide was reduced 71% and zomepirac renal clearance, a minor elimination route, was reduced by 79%. When assayed by a method that prevents degradation of the labile acyl glucuronide, zomepirac glucuronide concentrations in plasma were comparable to those of zomepirac. Probenecid decreased the renal clearance of zomepirac glucuronide by 72%, which, together with the increased zomepirac levels, resulted in a 2.8-fold increase in the AUC of the conjugate. Urinary excretion of zomepirac glucuronide was reduced from 72% to 58% of the dose, but the excretion of free zomepirac was unchanged at 5% of the dose. The ratio of the total clearance/bioavailability of zomepirac in control subjects was 682 +/- 246 ml/min, which is double the value reported in previous studies of zomepirac disposition. We believe that this difference is due to degradation of the unstable zomepirac acyl glucuronide in the previous analytic methodologies used. Qualitatively, the effects of probenecid on zomepirac disposition are similar to those previously reported for other drugs of this class that are metabolized to acyl glucuronides. However, zomepirac appears unusual in that significant levels of its acyl glucuronide metabolite are found in vivo.
Adult↗
Pharmacokinetics and dosage requirements of netilmicin in cystic fibrosis patients.
The pharmacokinetics of netilmicin were determined in 10 patients with cystic fibrosis. Mean (+/- standard error of the mean) values for total body clearance and volume of distribution were 2.62 (+/- 0.18) ml/min per kg of body weight and 0.38 (+/- 0.01) liter/kg, respectively, and were considerably larger than the same parameters reported for patients without cystic fibrosis.
Adolescent↗