PubMed Health⌕ Search

Biomedical subjects

M D Reed

Publications and source records attributed to M D Reed.

122 records · Page 7Linked to original sources
PubMedDate not supplied

Single-dose pharmacokinetics of aztreonam in children with cystic fibrosis.

The single-dose pharmacokinetics of aztreonam was evaluated in 10 clinically stable subjects with cystic fibrosis. Each child received 30 mg aztreonam/kg intravenously over 2 to 3 minutes. Multiple timed blood samples were obtained over 8 hours for determination of aztreonam elimination kinetics; all urine excreted for 24 hours was collected in timed aliquots for the determination of aztreonam and its microbiologically inactive metabolite, SQ 26,992. Aztreonam pharmacokinetic parameters were determined by model-independent methods. Mean t1/2, steady-state volume distribution, and body clearance were 1.3 hr, 0.25 L/kg, and 127.2 ml/min/1.73m2, respectively. In 9 of the 10 subjects, two-compartment pharmacokinetic analysis was possible and compared favorably with model-independent parameter estimates. Twenty-four-hour urinary recovery of aztreonam was 76.3% of the administered dose; 2.6% was recovered as the metabolite SQ 26,992. The renal clearance of aztreonam averaged 92.5 ml/min/1.73m2. When these data are combined with in vitro susceptibility data for aztreonam against Pseudomonas aeruginosa isolated from the sputum of patients with cystic fibrosis, a dose of 200 mg aztreonam/kg/day divided six hourly would be predicted to maintain serum concentrations above the minimum inhibitory concentration (MIC) for these organisms for the majority of the dosing interval.

Adolescent↗
PubMedDate not supplied

Therapeutic evaluation of piperacillin for acute pulmonary exacerbations in cystic fibrosis.

The efficacy and pharmacokinetics of piperacillin monotherapy were studied in 46 patients with cystic fibrosis. Two patients were dropped from the study within 24 hr of enrollment because of drug-associated nausea and vomiting. Initially fourteen older patients (greater than 12 years) receiving piperacillin 450 mg/kg/day underwent a preliminary evaluation. Based on the results, 30 younger patients (less than or equal to 12 years) randomized in a double-blind fashion received either 600 or 900 mg/kg/day of piperacillin in six divided doses. Pharmacokinetic parameter estimates for t1/2 Vdss, and Cl were similar for first dose and steady-state evaluations. In 27 patients, approximately 43% of the administered dose was recovered in the urine after 4 hr. Piperacillin CiR averaged 49% of the total Cl. No difference in overall clinical efficacy could be identified between 600 and 900 mg/kg/day of piperacillin using two different objective scoring systems. Although a reduction in sputum Pseudomonas colony counts was greater following the 900 mg/kg/day regimen, this appeared to be independent of clinical effect. In 14 patients (32%), a distinct adverse serum-sicknesslike reaction was observed. The incidence of this reaction appeared to increase as the dose of piperacillin increased. All signs and symptoms of this reaction resolved within 36 hr of discontinuing piperacillin administration but recurred immediately on rechallenge in four patients. All patients with the adverse reaction were subsequently treated with beta-lactam antibodies without ill effect. Overall, clinical improvement appeared to be independent of the piperacillin dose. Our data support the use of total daily piperacillin dosages not exceeding 600 mg/kg.

Adolescent↗
PubMedDate not supplied

Cyclic parenteral nutrition during allogeneic bone marrow transplantation.

Two adolescents who underwent successful allogeneic bone marrow transplantation were nutritionally managed on a fat-free cyclic parenteral nutrition (PN) regimen. Serum concentrations of prealbumin, albumin, and transferrin were prospectively evaluated to assess the efficacy of nutritional therapy. Both patients tolerated the cyclic PN metabolically. Serial albumin and transferrin concentrations varied slightly and were less sensitive indices of changing nutritional status. In contrast, prealbumin concentrations decreased uniformly during periods of metabolic stress. At the cessation of Pn therapy, all serum proteins were within the normal range. Cyclic PN appears to be a safe, practical approach to the nutritional management of patients undergoing bone marrow transplantation.

Adolescent↗
PubMedDate not supplied

Prophylaxis and treatment of childhood rickets with parenteral cholecalciferol.

The safety and efficacy of parenteral cholecalciferol was evaluated in the treatment and prevention of childhood rickets. Children with active disease, and those at high risk for developing rickets were treated either with intravenous or intramuscular cholecalciferol in dosages of 1000 to 1500 IU daily, for periods of 28 to 450 days. All children with rickets responded with radiographic evidence of healing. No child in the prophylaxis group developed bone disease. Side effects were minimal. Parenteral cholecalciferol is a safe and effective therapy for the treatment and prevention of childhood rickets.

Alkaline Phosphatase↗
PubMedDate not supplied

Developmental pharmacology: relationship to drug use.

The pharmacodynamics of drugs in children have been poorly understood, and only recently have technological advances permitted the issue to be studied. Factors that affect drug use in infants include absorption, distribution, protein binding, metabolism, renal elimination, and volume of distribution. Selection of antibiotics in this patient population should reflect commonly isolated organisms, such as staphylococci, group B streptococci, Escherichia coli, and gram-negative bacteria. An antibiotic must also have good penetration into the central nervous system. Displacement of bilirubin from its albumin-binding sites by drugs or endogenous substrates can lead to kernicterus, or bilirubin encephalopathy. The free bilirubin, rather than total concentration, appears to be only partly responsible for the development of kernicterus.

Aging↗
PubMedDate not supplied

Pharmacological treatment of depression in children and adolescents.

Major depression is a common disorder during childhood and adolescence. Over the past decade, many new antidepressants have been marketed in the US. In adults, these newer agents have been shown to be as effective as the prototypic tricyclic antidepressants (TCAs). Further, when compared with the TCAs these medications are better tolerated and are safer in overdose. Although TCAs are effective in the treatment of depressed adults, controlled clinical trials have not demonstrated their efficacy in either children or adolescents. In addition, concerns about the safety of TCAs and the monoamine oxidase inhibitors has left disappointingly few pharmacological treatment options available for depressed children and adolescents. For this reason, clinicians have begun to prescribe the newer agents for this population, despite the fact that relatively little is known about their disposition, safety or effectiveness in the young. Investigators have begun to examine whether the use of newer antidepressant medications such as fluoxetine, sertraline, paroxetine, fluvoxamine, nefazodone, and venlafaxine is truly indicated for children and adolescents with major depression. Pharmacokinetic studies of sertraline, paroxetine and nefazodone have been performed in depressed youths. The results of these studies have provided data for rational administration strategies for these agents. They have also provided evidence that these agents may be well tolerated in children and adolescents. Further evidence that these agents are often well tolerated when prescribed to depressed youths has been obtained from both open-label and double-blind studies. Published studies have generally shown that open-label treatment with these newer agents often leads to symptom amelioration in paediatric patients with major depression. Since high rates of placebo response are often seen in depressed children and adolescents, results from these studies cannot be interpreted to suggest that these medications have true antidepressant efficacy in this population. At present, the results of only two such studies have been published. The results of one of these trials are difficult to interpret because of methodological considerations. The other study reported that treatment with fluoxetine was superior to placebo. This paper critically reviews what has been published about the pharmacological treatment of depressed paediatric patients and provides some guidance to the use of antidepressants in this patient population, paying particular attention to what is known about the newer antidepressants as well as considering directions for future research.

Adolescent↗
PubMedDate not supplied

High-dose i.v. thiotepa and cryopreserved autologous bone marrow transplantation for therapy of refractory cancer.

Twenty-five patients with malignancies resistant to conventional chemoradiation therapy or for which no effective therapy is known were treated with escalating doses of thiotepa (135-1215 mg/m2 iv over 3 days) followed by reinfusion of previously cryopreserved autologous bone marrow. The hematological and nonhematological toxic effects, therapeutic effects, and pharmacokinetics of this regimen were evaluated. Granulocyte (greater than 500/microliter) and platelet (greater than 20,000/microliter) count recovery occurred at a median of 16 (range, 11-38) and 18.5 (range, 11-40) days after marrow reinfusion, respectively. Six patients experienced severe infection, four of which were fatal. One patient died due to intracranial hemorrhage. Toxicity to the gastrointestinal and central nervous systems was dose-limiting, and the maximum tolerated dose of thiotepa was 1005 mg/m2. Objective tumor regression occurred in six of the patients. Serum thiotepa concentration peaked immediately after infusion and declined rapidly in a biphasic manner. No relationship between thiotepa serum concentration or pharmacokinetic parameter estimates was observed for tumor response or toxicity. High-dose thiotepa and autologous bone marrow transplantation may represent an alternative therapeutic modality for patients with advanced cancer.

Adolescent↗
PubMedDate not supplied

Evaluation of moxalactam.

The mechanism of action, antibacterial spectrum, pharmacokinetics, current dosage recommendations, adverse reactions, therapeutic uses, and pharmaceutical considerations of moxalactam disodium are reviewed. Moxalactam is a synthetically derived, structurally unique beta-lactam antibiotic. Its antimicrobial activity encompasses a wide spectrum and includes some strains of pseudomonal species. Administered by i.v. or i.m. injection, moxalactam is widely distributed to body fluids and tissues. Its elimination half-life is longer than those of first- and second-generation cephalosporins. Usually administered in two or three divided doses daily, moxalactam has been shown to be effective against specific organisms in a variety of infections, including lower respiratory, urinary-tract, intra-abdominal, central nervous system, skin and skin-structure, and bone and joint infections, and bacterial septicemia. Adverse reactions associated with moxalactam administration have been limited and appear similar to those experienced following the use of other beta-lactam antibiotics. Because of its wide spectrum of activity, colonization of resistant organisms and (to a lesser extent) superinfection may complicate therapy. Early clinical experience indicates that moxalactam is effective for the treatment of a number of bacterial infections, including those involving the abdominal cavity and respiratory and urinary tracts. More experience is necessary to delineate its most appropriate roles in specific infectious processes.

Bacteria↗
PubMedDate not supplied

Single-dose plasma and cerebrospinal fluid pharmacokinetics of ceftriaxone in infants and children.

Pharmacokinetic variables were studied in children with central nervous system infections who received a single dose of ceftriaxone sodium. After initial lumbar puncture of children with documented or suspected bacterial meningitis, ventriculitis, or both, therapy was initiated with i.v. ampicillin and chloramphenicol. Children were randomly selected to receive a single i.v. dose of ceftriaxone. Concentrations of ceftriaxone were measured in plasma at intervals from 0 to 720 minutes after the beginning of the infusion and in cerebrospinal fluid (CSF) at one to five hours after the dose. Blood samples were obtained immediately after the second lumbar puncture for assessment of drug penetration into CSF. Elimination rate constant, elimination half-life, apparent volume of distribution, and plasma clearance were determined from samples obtained 30-720 minutes after the start of the infusion. In two children with ventriculoperitoneal shunts, serial determinations of ceftriaxone in CSF were obtained. All eight children who received 75 mg/kg and five of eight who received 50 mg/kg had positive CSF cultures. Volume of distribution was less after the 50 mg/kg dose than after the 75 mg/kg dose. In the children with shunts, adequate CSF drug concentrations were maintained throughout 12 hours of testing. These data support a 12-hour dosage interval, but clinical studies are needed to evaluate efficacy of the drug at both 12-hour and 24-hour dosage regimens.

Adolescent↗
PubMedDate not supplied

Propylene glycol: the safe diluent that continues to cause harm.

Propylene glycol (PG) is present in many pharmaceutical products, lotions, ointments, and cosmetics. Although considered to be a relatively safe substance, overdoses have been associated with serious adverse effects. Propylene glycol intoxication occurred in a child and caused central nervous system depression and a severe metabolic acidosis. Initial assessment revealed an elevated serum anion gap, a slight increase in measured serum osmolality, and a normal osmolal gap. The child's acidosis was due to increased concentrations of lactate and pyruvate. The possibility of serious PG intoxication should be considered in any patient with an unexplained serious metabolic acidosis.

Acidosis↗
PubMedDate not supplied

Pharmacokinetics of azithromycin after single- and multiple-doses in children.

STUDY OBJECTIVE: To characterize the disposition and tolerance of azithromycin after single and multiple oral doses of 12 mg/kg in children with and without cancer. DESIGN: Open-label, nonrandomized pharmacokinetic study. SETTING: Two pediatric hospitals. PATIENTS: Twelve children with cancer admitted to the inpatient unit for empiric antibiotic treatment of febrile neutropenia, and 16 hospitalized patients receiving antibiotic therapy INTERVENTIONS: Patients received azithromycin suspension either as a single dose or daily dose every morning for 5 consecutive days. Serial blood samples were collected up to 120 hours after a single dose or during and after multiple doses to characterize the pharmacokinetic parameters estimated for a two-compartment absorption model. MEASUREMENTS AND MAIN RESULTS: All 28 patients were evaluable for safety. Azithromycin was well tolerated except in one patient with cancer who experienced abdominal cramps and withdrew from the study. Pharmacokinetic results were not determined in five patients because of insufficient concentration-time data. The mean +/- SD estimates of oral clearance, terminal half-life, maximum concentration in serum (Cmax), and time to achieve Cmax in the 23 evaluable patients were 4.83 +/- 3.59 L/hour/kg, 54.5 +/- 36.4 hours, 318.2 +/- 174.5 microg/L, and 2.4 +/- 1.1 hours, respectively. These estimates did not differ between single-dose (14 patients) and multiple-dose (9 patients) groups. Pharmacokinetic parameters were not different between the 11 children with cancer and the 12 without cancer. CONCLUSION: Azithromycin 12 mg/kg results in proportionately higher serum concentrations than previously published results for lower doses (5 mg/kg). Variability in concentration profiles among patients is substantial, and age or other yet unidentified clinical factors may explain some of the differences observed.

Adolescent↗