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Biomedical subjects

J L Blumer

Publications and source records attributed to J L Blumer.

At least 127 records · Page 7Linked to original sources
PubMed1985

Pharmacokinetics of imipenem and cilastatin in patients with cystic fibrosis.

The pharmacokinetics of imipenem, a new carbapenem antibiotic, and cilastatin, a metabolic inhibitor, were evaluated in 17 patients with cystic fibrosis. Imipenem and cilastatin were combined in a ratio of 1:1 in the infusion solution, and patients intravenously received 30, 60, or 90 mg of imipenem per kg of body weight per day, divided into four equal doses. Pharmacokinetic evaluation after the first dose and again under steady-state conditions revealed biodisposition characteristics which were similar and independent of the daily dose administered. Cilastatin concentrations in serum paralleled those of imipenem. A linear relationship between dose and area under the serum concentration-time curve for both compounds was observed, suggesting a first-order pharmacokinetic process. A total of 50 and 78% of the doses of imipenem and cilastatin, respectively, were recovered unchanged in the urine. The renal clearances of imipenem and cilastatin averaged 54 and 88%, respectively, of the serum clearance. These data suggest that an extrarenal mechanism may be involved in the overall elimination of imipenem. No patient experienced any clinical or biochemical abnormalities during drug therapy.

Anti-Bacterial Agents↗
PubMed1985

Cerebrospinal fluid penetration of moxalactam in ventriculostomy patients.

The cerebrospinal fluid penetration of moxalactam was simultaneously investigated in three patients with presumed bacterial meningitis. When ratios of simultaneously drawn ventriculostomy to serum moxalactam levels of 1, 2, 3, and 4 h were examined, the penetration ratios were 7.8 +/- 2.4, 11.2 +/- 1.3, 14.2 +/- 2.5, and 15.0 +/- 4.9%, respectively. These ratios were not statistically different from the penetration of moxalactam calculated by the area under the concentration-time curve technique (8.97 +/- 1.89%).

Drug Administration Schedule↗
PubMed1985

Pharmacokinetics and cerebrospinal fluid penetration of ceftazidime in children with meningitis.

The single dose pharmacokinetics and cerebrospinal fluid (CSF) penetration of ceftazidime were determined in 10 children with bacterial meningitis. Serum ceftazidime pharmacokinetics showed a distinct age dependence in which the clearance in children less than 1 month of age was markedly reduced. Ceftazidime concentrations in CSF, which ranged from 1.4-8.5 micrograms/ml, exceeded the minimum bactericidal concentrations for infecting pathogens throughout the 8-hour sampling period. These concentrations were found to be independent of CSF cell count, protein concentration or the day of therapy on which the study was performed. The ratio of CSF to serum ceftazidime concentration increased with time, suggesting that ceftazidime was cleared more slowly from CSF than from peripheral blood. Our data support the initiation of a study comparing the efficacy of ceftazidime to conventional therapy in children with bacterial meningitis.

Age Factors↗
PubMed1985

Relationship between the oxidation potential of benzene metabolites and their inhibitory effect on DNA synthesis in L5178YS cells.

The effects of benzene and its metabolites on the rate of DNA synthesis were measured in the mouse lymphoma cell line, L5178YS. The direct toxicity of benzene could be distinguished from that of its metabolites since bioactivation of benzene in L5178YS cells was not observed. Cells were exposed to benzene, phenol, catechol, hydroquinone, p-benzoquinone, or 1,2,4-benzenetriol over the range of 1.0 X 10(-7) to 1.0 X 10(-2) M for 30 min, and the rate of DNA synthesis was measured at various times after chemical washout. Cell viability and protein synthesis were determined by trypan blue dye exclusion and [3H]leucine incorporation, respectively. Effects were designated as "DNA specific" when DNA synthesis was inhibited in the absence of discernible effects on cell membrane integrity and protein synthesis. Concentrations of benzene as high as 1 mM had no effect on DNA synthesis. Comparison of the effects at the maximum nontoxic dose for each compound showed that catechol and hydroquinone were the most effective, inhibiting DNA synthesis by 65%. Phenol, benzoquinone, and benzenetriol inhibited DNA synthesis by approximately 40%. Maximum inhibition was observed 60 min after metabolite washout in each case. Benzoquinone was the most potent inhibitor of DNA synthesis, followed by hydroquinone, benzenetriol, catechol, and phenol with ED50 values of 5 X 10(-6), 1 X 10(-5), 1.8 X 10(-4), 2.5 X 10(-4), and 8.0 X 10(-4), respectively. Cyclic voltammetric experiments were performed on the hydroxylated metabolites of benzene to assess the possible involvement of a redox-type mechanism in their inhibition of DNA synthesis. The ease of oxidation of these metabolites correlated with their ED50 values for inhibition of DNA synthesis (r = 0.997). This suggests that oxidation of phenol or one of its metabolites may be necessary for production of the species involved in inhibition of DNA synthesis.

Animals↗
PubMed1984

Dosing implications of rapid elimination of trimethoprim-sulfamethoxazole in patients with cystic fibrosis.

The first-dose and steady-state pharmacokinetics of trimethoprim and sulfamethoxazole were determined in 14 patients with cystic fibrosis. When pharmacokinetic data from the first dose were compared with those at steady state, both TMP and SMZ showed expected accumulations in serum concentrations and decreases in total body clearance. The area under the SMZ serum concentration-time curve was significantly greater at steady state, suggesting drug accumulation during long-term therapy. When pharmacokinetic characteristics for TMP and SMZ obtained in patients with cystic fibrosis were compared with those reported for normal adults, the patients were found to have shorter elimination half-lives and greater plasma clearances. In addition, the apparent volume of distribution for TMP was smaller for patients with cystic fibrosis than for normal adults, consistent with their reduced mass of adipose tissue. Our data support the need for increased dosing or decreased dosing intervals when administering TMP-SMZ to patients with cystic fibrosis.

Adolescent↗
PubMed1984

Comparison of the efficacy and safety of ceftriaxone to ampicillin/chloramphenicol in the treatment of childhood meningitis.

Ceftriaxone is a new cephalosporin with a broad spectrum of antibacterial activity and unique serum and CSF pharmacokinetics. The drug was compared in a randomized fashion with ampicillin and chloramphenicol in the treatment of 19 children with Haemophilus influenzae type b meningitis. Ceftriaxone was also administered non-randomly to six other patients including three children with Gram-negative meningitis. Among the children with H. influenzae meningitis, no deaths were noted and the outcomes of the study and the control groups were similar. Ninety per cent of the isolates of H. influenzae were inhibited by 0.0625, 1 and 1 mg/l of ceftriaxone, ampicillin and chloramphenicol respectively. One child with pneumococcal meningitis and two children with meningococcal meningitis recovered rapidly and without incident during ceftriaxone therapy. Three children with Gram-negative meningitis caused by multiply-drug resistant organisms were bacteriologically cured within five days of the onset of therapy. Persistent pleocytosis and neurological disabilities were noted in two at the conclusion of therapy. Ceftriaxone, as a single agent, was comparable in efficacy with traditional antimicrobial therapy usually employed in childhood meningitis.

Adolescent↗
PubMed1984

A double-blinded comparative study of sultamicillin and potassium penicillin V in the treatment of childhood streptococcal pharyngitis.

Fifty-two children with positive pharyngeal cultures for group A streptococci were randomized to receive phenoxymethyl penicillin or sultamicillin, an ester of ampicillin and sulbactam. By serological and bacteriological criteria, sultamicillin was effective in 100% of the 20 evaluable cases of infection and carriage while penicillin was effective in six out of eight (75%) and three out of eight (93%) respectively. Of the eight children with infections treated with sultamicillin, three (37.5%) became recolonized with the organism compared to none of the children in the penicillin group. These differences were not statistically significant.

Adolescent↗
PubMed1984

Determination of cefsulodin in biological fluids by high-pressure liquid chromatography.

Cefsulodin is a third-generation cephalosporin with a unique specificity for Pseudomonas aeruginosa. To study the pharmacokinetics of this agent in children, a rapid and sensitive high-performance liquid chromatographic micromethod was developed for plasma and urine. Protein was precipitated from plasma with one volume of cold methanol, and 20 microliter of the resulting supernatant solution was injected into a Zorbax C-8 reversed-phase column. The mobile phase was composed of 4.5 parts acetonitrile and 95.5 parts of 0.035 M ammonium acetate buffer (pH 5.2). Flow rate was 1.0 ml/min and peaks were detected at 265 nm. A flow gradient from 0.3 to 2.0 ml/min over 34 min was employed for urine. The analysis had a limit of detectability of 1 microgram/ml and a between-day coefficient of variation of 4.4 and 5.0 for 100 and 10 micrograms/ml samples, respectively.

Body Fluids↗
PubMed1984

Single-dose pharmacokinetics of cefsulodin in patients with cystic fibrosis.

The single-dose pharmacokinetics of cefsulodin were evaluated in 12 patients with cystic fibrosis. Each patient received 3 g of cefsulodin intravenously over 30 min. Multiple plasma and urine samples were obtained during the 6-h study period for the determination of cefsulodin. Pharmacokinetic parameters were determined by model-independent methods. Mean values for t1/2, Vss, and CLp were 1.53 h, 0.242 liters/kg, and 117.3 ml/min per 1.73 m2, respectively. Six-hour urine recovery revealed 73.2% of the administered dose with a corresponding cefsulodin urinary clearance of 75.1 ml/min. These pharmacokinetic data in patients with cystic fibrosis appear consistent with data reported for unaffected individuals.

Adolescent↗
PubMed1984

Determination of imipenem and cilastatin in serum by high-pressure liquid chromatography.

Imipenem and cilastatin concentrations in serum were determined by using reverse-phase high-pressure liquid chromatography. Serum samples were stabilized with 0.5 M morpholineethanesulfonic acid buffer (pH 6.0) and subjected to ultrafiltration before chromatography. The elution solvent consisted of water or potassium phosphate buffered to pH 2.5 and methanol. The imipenem and cilastatin peaks were detected at 300 and 220 nm, respectively. Recovery from serum was 99% for both imipenem and cilastatin, and the limits of detectability for the two compounds were 0.3 and 0.5 microgram/ml, respectively. The assay may be readily applied to pharmacokinetic analysis of imipenem and cilastatin biodisposition in patients.

Anti-Bacterial Agents↗
PubMed1984

Ceftazidime as initial therapy for suspected bacterial infections in hospitalized pediatric patients.

Ceftazidime, a new beta-lactam antibiotic, was used to treat 60 children with suspected bacterial infections occurring outside the central nervous system. The patients ranged in age from 0.1 to 21 years and received 30 mg of ceftazidime per kg up to a total single dose of 1 g administered every 8 h. Fifty-three pathogens were isolated from 43 children before the initiation of therapy. All children responded clinically, although one child failed bacteriologically and five children were considered colonized at the end of ceftazidime therapy. Adverse reactions associated with ceftazidime administration were primarily alterations in laboratory parameters and were clinically insignificant. Ceftazidime administered on an 8-h dosing regimen is effective monotherapy for the treatment of childhood infections.

Adolescent↗
PubMed1984

Evaluation of latamoxef as initial therapy of bone and joint infections in childhood.

The efficacy and pharmacokinetics of latamoxef were evaluated during initial therapy of bacteriologically proven bone and joint infections in children. Pharmacokinetic evaluation revealed no significant difference in latamoxef biodisposition after the first dose or at steady state. Peak serum concentrations exceeded 140 mg/l and 8-hour trough concentrations averaged 6.5 mg/l. The patients were infected with a variety of gram-positive and gram-negative pathogens. All were sensitive to readily achievable serum concentrations of latamoxef; moreover, the serum concentration remained above the MIC of the most resistant organism for at least 7 h after each dose. All patients responded favorably to initial therapy and there have been no relapses in more than 2 years of clinical follow-up.

Adolescent↗
PubMed1984

Moxalactam therapy of serious pediatric infections.

Forty children with documented or suspected bacterial infections arising outside the central nervous system (CNS) were studied. Fifteen different pathogens for a total of 30 isolates were obtained from multiple sources. Staphylococcus aureus (minimum inhibitory concentrations 4-8 micrograms/ml) was the most common pathogen isolated, involving seven patients. Each patient received moxalactam 50 mg/kg iv over 15 minutes q8h and responded favorably to therapy, exhibiting bacteriologic and/or clinical cures. Toxicity associated with moxalactam occurred in only two patients and necessitated discontinuation of drug therapy. Moxalactam 50 mg/kg iv q8h is effective therapy for non-CNS infections occurring in infants and children.

Bacteria↗
PubMed1983

Determination of amiodarone and its N-deethylated metabolite in serum by high-performance liquid chromatography.

A high-performance liquid chromatographic (HPLC) method utilizing hexane extraction and a normal bonded phase column (NH2-alkylamine) was developed to measure serum concentrations of amiodarone and its N-deethylated metabolite. A single analysis requires 8 min. The one-step extraction efficiencies of amiodarone and the internal standard are greater than 90%. The method is linear between 0.05 and 20.0 micrograms/ml. The average relative standard deviation of the slope of the standard curve is 4% and the single day coefficient of variation is 3.2%. The use of hexane extraction for sample cleanup and a bonded phase column for chromatography result in a sensitive and reproducible system well suited to laboratories monitoring serum concentrations of multiple drugs by HPLC. A preliminary study has shown the assay to be useful for the investigation of the pharmacokinetics of this agent.

Adult↗
PubMed1983

Cyclic parenteral nutrition during bone marrow transplantation in children.

Nine children underwent ten bone marrow transplants for malignancies and were supported by parenteral alimentation administered in cyclic fashion 18 hours daily. Children received cyclic parenteral nutrition for an average of 29 days, which provided a caloric intake (mean +/- SD) of 55.9 +/- 18.1 Kcal/kg/day, and a nitrogen intake of 0.28 +/- 0.08 g/kg/day. Nutritional status was assessed using nitrogen balance, creatinine-height index, and visceral protein concentrations including serum albumin, transferrin, and prealbumin. Minimal transient elevation in tests of liver function were observed without marked derangement in blood glucose, electrolytes, or osmolality. Unlike prealbumin, determinations of nitrogen balance, creatinine-height index, serum albumin and transferrin concentrations did not parallel changes in clinical status. Cyclic parenteral alimentation is a practical approach to the maintenance of nutrition during intensive antitumor therapy and provides an infusion-free period for the administration of drugs and blood transfusions without interfering with nutritional support. Prealbumin accurately reflects changes in the patient's clinical status at any point and is easily and reliably determined.

Adolescent↗
PubMed1983

Clinical pharmacology of antitubercular drugs.

Isoniazid, rifampin, and ethambutol are the three major drugs used in the modern treatment of patients with tuberculosis. Data on these drugs in children have been derived primarily from their clinical use in pediatrics and extrapolation from experiences in adults. A number of questions remain concerning the clinical pharmacology and appropriate use of these drugs in children. Additional pediatric pharmacokinetic studies are necessary to confirm the current dosage recommendation and use of these agents in the pediatric patient.

Antitubercular Agents↗