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M D Reed

Publications and source records attributed to M D Reed.

At least 55 records · Page 3Linked to original sources
PubMed1995

Sequential, single-dose pharmacokinetic evaluation of meropenem in hospitalized infants and children.

Meropenem is a new carbapenem antibiotic which possesses a broad spectrum of antibacterial activity against many of the pathogens responsible for pediatric bacterial infections. In order to define meropenem dosing guidelines for children, an escalating, single-dose, pharmacokinetic study at 10, 20, and 40 mg/kg of body weight was performed. A total of 73 infants and children in four age groups were enrolled in the study: 2 to 5 months, 6 to 23 months, 2 to 5 years, and 6 to 12 years. The first patients enrolled were those in the oldest age group, who received the lowest dose. Subsequent enrollment was determined by decreasing age and increasing dose. Complete studies were performed on 63 patients. No age- or dose-dependent effects on pharmacokinetic parameter estimates were noted. Mean pharmacokinetic parameter estimates were as follows: half-life, 1.13 +/- 0.15 h; volume of distribution at steady state, 0.43 +/- 0.06 liters/kg; mean residence time, 1.57 +/- 0.11 h; clearance, 5.63 +/- 0.75 ml/min/kg; and renal clearance, 2.53 +/- 0.50 ml/min/liters kg. Approximately 55% of the administered dose was recovered as unchanged drug in the urine during the 12 h after dosing. No significant side effects were reported in any patients. By using the derived pharmacokinetic parameter estimates, a dose of 20 mg/kg given every 8 h will maintain plasma meropenem concentrations above the MIC that inhibits 90% of strains tested for virtually all potentially susceptible bacterial pathogens.

Aging↗
PubMed1995

Recent advances in pediatrics.

The challenging issues in pediatric pharmacotherapy are both profound and exciting. Microtechnologies for evaluating the impact of genetics in disease (e.g., using polymerase chain reactions) and the possibilities of therapeutic interventions create major clinical and ethical dilemmas that remain to be resolved. Inclusion of pediatric patients in drug development and marketing trials also remains a point of contention. Finally, well-established therapies should not be overlooked in favor of new but unestablished treatment approaches. Future columns will continue to use the current format, in which a few selected topics of high therapeutic importance are discussed. The research technologies, discussion of new drug therapy interventions, and preventive strategies most likely to benefit the health care of infants, children, and adolescents will remain the scope of this column.

Adolescent↗
PubMed1994

Therapeutic drug monitoring in the pediatric intensive care unit.

Drugs are administered in the pediatric intensive care unit using either a target-effect or a target-concentration strategy. In the former, drug dose is escalated until the predetermined target-effect is achieved, no further pharmacologic effect is obtained with incremental increases in dose, or toxicity supervenes. When the target-concentration strategy is used, drug therapy is adjusted to achieve serum/plasma drug concentrations within an accepted therapeutic range. This strategy does not recognize interindividual differences in drug responsiveness. Therapeutic drug monitoring in the pediatric intensive care unit is further confounded by the limited data available concerning the effects of the other technologies used on drug disposition and the paucity of information related to therapeutic agents in pediatric patients. Clearly therapeutic drug monitoring in the pediatric intensive care unit is a daunting challenge.

Adolescent↗
PubMed1994

Single-dose pharmacokinetics of piperacillin and tazobactam in infants and children.

The pharmacokinetics of piperacillin and tazobactam were assessed after single-dose administration to 47 infants and children. Study subjects ranging in age from 2 months to 12 years were randomized to receive one of two different doses of a piperacillin-tazobactam combination (8:1): a low dose (n = 23) of 50 and 6.25 mg of piperacillin and tazobactam per kg of body weight, respectively, or a high dose (n = 24) of 100 and 12.5 mg, respectively. The pharmacokinetic behavior of tazobactam was very similar to that observed for piperacillin, supporting the use of these two agents in a fixed-dose combination. No differences in the pharmacokinetics of piperacillin or tazobactam were observed between the two doses administered. The elimination parameters half-life and total body clearance decreased and increased, respectively, with increasing age, whereas volume parameters (volume of distribution and steady-state volume of distribution) remained relatively constant for both compounds. The primary metabolite of tazobactam, metabolite M1, was measurable in the plasma of 18 of the 47 study subjects; 17 of these 18 subjects received the high doses. More than 70% of the administered piperacillin and tazobactam doses were excreted unchanged in the urine over a 6-h collection period. These data combined with the known in vitro susceptibilities of a broad range of pediatric bacterial pathogens indicate that a dose of 100 mg of piperacillin and 12.5 of mg tazobactam per kg of body weight administered as a fixed-dose combination every 6 to 8 h would be appropriate to initiate clinical efficacy studies in infants and children for the treatment of systemic infections arising outside of the central nervous system.

Child↗
PubMed1994

Ondansetron for treating nausea and vomiting in the poisoned patient.

OBJECTIVE: To describe the efficacy of ondansetron for the treatment of poisoning-associated vomiting in two patients following drug intoxication. PATIENTS: Two self-poisoned adolescent patients. INTERVENTION: Intravenous ondansetron. RESULTS: Resolution of nausea and vomiting in both patients. CONCLUSIONS: Ondansetron appears to be a very effective antiemetic drug for use in selected intoxicated patients.

Acetaminophen↗
PubMed1994

Racemic versus l-epinephrine aerosol in the treatment of postextubation laryngeal edema: results from a prospective, randomized, double-blind study.

OBJECTIVE: To determine whether any advantage exists using racemic epinephrine instead of the more potent and less expensive levo(1)-epinephrine in the treatment of postextubation laryngeal edema. DESIGN: Prospective, double-blind, randomized study. SETTING: Pediatric intensive care unit in a university teaching hospital. PATIENTS: Twenty-eight patients with stridor during the immediate postextubation period. INTERVENTIONS: After extubation, patients demonstrating clinically important stridor were randomized in a double-blind fashion to receive an aerosol containing either 2.25% racemic or 1% l-epinephrine. MEASUREMENTS AND MAIN RESULTS: Heart rate, respiratory rate, blood pressure, and stridor score were determined at 20, 40, and 60 mins and 4 and 8 hrs after the initial aerosol administration. Patients in both groups demonstrated significant (p < .01) reductions in stridor score after aerosol administration. No significant differences were observed between treatment groups in improvement in stridor score or the number of subsequent aerosols required. Respiratory rate decreased significantly 40 and 60 mins after l-epinephrine but not after racemic epinephrine. No significant change in heart rate or blood pressure occurred after aerosol administration in either group. CONCLUSIONS: These data suggest that aerosolized l-epinephrine is as effective as aerosolized racemic epinephrine in the treatment of postextubation laryngeal edema without additional adverse side effects. When dosed appropriately, l-epinephrine is a less expensive and more widely available alternative to racemic epinephrine for the treatment of postextubation laryngeal edema.

Aerosols↗
PubMed1993

Sudden death and bereavement outcomes: the impact of resources on grief symptomatology and detachment.

The study of sudden bereavement focuses almost exclusively on its impact on psychological well-being. This research broadens our understanding of bereavement outcomes by exploring the effect of grief on family detachment following sudden bereavement. Moreover, this study examines the relative contributions of resources in alleviating grief symptoms and reducing detachment. Data are collected from medical examiner records and mail-back surveys from family members of victims of suicide and accidental deaths in a large metropolitan area of the United States. A covariance structural equation model allowing for correlated measurement error is estimated using LISREL VII. The results indicate that the most grief-stricken survivors are more detached from family than those who are least grief-stricken. Examination of the direct and indirect influences of resources on bereavement outcomes reveals that self-esteem is the strongest predictor of grief and that it also plays a decisive role in mediating the influences of religious participation and exercise on grief. Expressive support exerts direct effects on both grief and detachment. This research concludes by directing future research to examine more fully the impact of sudden bereavement on marital and family relationships.

Adolescent↗
PubMed1992

Effect of extracorporeal membrane oxygenation on tobramycin pharmacokinetics in sheep.

BACKGROUND AND METHODS: Critically ill infants undergoing extracorporeal membrane oxygenation (ECMO) therapy often receive multiple pharmacologic agents. Although the disposition of many drugs has been assessed in patients undergoing cardiopulmonary bypass and in patients receiving mechanical ventilation, only limited data exist for selected medications in patients undergoing ECMO. To evaluate the potential influence of ECMO on aminoglycoside pharmacokinetics, we studied the disposition of tobramycin in ten sheep before and during ECMO therapy. Each sheep received a single iv dose of tobramycin during a control period before ECMO and on a study day during ECMO. Identically timed serial blood samples over 4 hrs were obtained after each tobramycin dose. Paired serum tobramycin concentrations were obtained pre- and postmembrane oxygenator during ECMO in six sheep. RESULTS: Alterations in specific pharmacokinetic variables for tobramycin were observed as a result of ECMO. Estimates of elimination half-life and volume of distribution for tobramycin were significantly increased during ECMO as compared with control (pre-ECMO) values (1.8 +/- 0.3 vs. 2.7 +/- 0.8 [SD] hrs [p < .01] and 0.3 +/- 0.1 vs. 0.5 +/- 0.2 L/kg [p < .005], respectively). Tobramycin body clearance was unaffected by the procedure (1.8 +/- 0.8 vs. 1.7 +/- 0.4 mL/min/kg). Paired serum tobramycin concentrations obtained pre- and postmembrane oxygenator demonstrated no drug removal. CONCLUSIONS: These data suggest that ECMO circuitry does not sequester tobramycin and that the prolonged elimination half-life observed during ECMO therapy is not due to a change in drug clearance but is due to an ECMO-induced increase in tobramycin volume of distribution. To achieve and maintain preselected target tobramycin serum concentrations during ECMO, the usual dosage interval should remain unchanged, but the dose should be increased to compensate for the alteration in the drug's volume of distribution. The clinical applicability of these findings needs to be confirmed in carefully controlled clinical studies involving infants receiving ECMO therapy.

Animals↗
PubMed1991

Influence of infusion pumps on the pharmacologic response to nitroprusside.

OBJECTIVE: To compare the relationship between variability in nitroprusside delivery from five infusion pumps and the resulting variability in mean arterial pressure (MAP). DESIGN: Randomized, crossover study design. SETTING: A pediatric ICU in a university hospital. PATIENTS: Informed parental consent was obtained for six patients who were hemodynamically stable and receiving a continuous nitroprusside infusion for a clinical application. Subjects ranged in age from 11 months to 9 yr. INTERVENTIONS: All of the subjects were administered nitroprusside using selected infusion pumps, which included Abbott (Micro), 3M/AVI (210), IMED (965), IVAC (565), and Kendall McGaw (MicroRate). MEASUREMENTS AND MAIN RESULTS: After an initial equilibration interval for each device, MAP was measured and recorded at 10-sec intervals for greater than or equal to 90-min intervals using a computerized data collection technique. Variation in nitroprusside administration (flow continuity) for each infusion pump was determined in vitro using a computerized gravimetric technique. Variation in both MAP and flow continuity was mathematically expressed as the coefficient of variance (CV) of the measured values for each of the respective infusion pumps. For the Abbott, IMED, 3M/AVI, IVAC, and Kendall McGaw, infusion pumps, mean +/- SD continuity CV values were 85 +/- 31%, 39 +/- 26%, 19 +/- 8%, 17 +/- 3%, and 12 +/- 3%, respectively, and MAP CV values were 18 +/- 21%, 15 +/- 11%, 8 +/- 2%, and 16 +/- 10%, respectively. CONCLUSIONS: An apparent direct relationship between MAP variability and flow continuity was observed. We speculate that variation in effect of potent short-acting drugs may, in part, be due to infusion pump operation.

Blood Pressure↗
PubMed1991

Single-dose pharmacokinetics of ceftibuten (SCH 39720) in infants and children.

Ceftibuten (CFB), a new broad-spectrum cephalosporin for oral administration, possesses potent activity in vitro against a wide range of gram-negative and certain gram-positive pathogens frequently encountered in pediatric patients. Its antimicrobial spectrum and dosage formulation suggest a use for CFB in the treatment of otitis media and upper and lower respiratory and urinary tract infections in infants and children. To assess the pharmacokinetic characteristics of CFB in pediatric patients, we completed a multicenter investigation of 49 children (26 females) between the ages of 6 months and 17 years who had normal hepatic and renal functions and no evidence of chronic disease. Pharmacokinetic parameters were determined from repeated blood samples (n = 12) and, when possible, quantitative urine collections (n = 7) obtained over a 12- to 24-h period following a single oral CFB dose of either 4.5 or 9.0 mg/kg of body weight. CFB was quantitated from plasma and urine samples by using a sensitive, microanalytical high-pressure liquid chromatography method. The drug was rapidly absorbed (mean time to maximum concentration in serum = 140 min) and produced apparent peak concentrations in plasma (Cmax) ranging from 5.0 to 19.0 mg/liter. Average CFB pharmacokinetic parameters (+/- standard deviations) were as follows: apparent elimination half-life, 2.0 +/- 0.5 h; mean residence time, 3.9 +/- 1.1 h; apparent steady-state volume of distribution, 0.4 +/- 0.2 liter/kg; and apparent total plasma clearance (CL/F), 2.5 +/- 0.9 ml/min/kg. No significant differences in any of the pharmacokinetic parameters were observed between the two dosing groups. Significant (P < 0.05) negative correlations were found between patient age and CFB elimination half-life and CL/F and between the estimated creatinine clearance and renal clearance and CL/F. Apparent age dependence of CFB disposition was also reflected by a greater CL/F in children from 0.5 to less than or equal 5 years of age (3.1 +/- 1.1 ml/min/kg) than in children > 10 years of age (2.0 +/- 0.6 ml/min/kg; P < 0.005). The increased CL/f for CFB (3.0 +/- 0.5 ml/min/kg) was corroborated by a validation study performed with 11 infants (1.0 +/- 0.5 ml/min/kg) with CL/F for 19 subjects suggested that appreciable nonrenal clearance (1.3 +/- 0.6 ml/min/kg) of CFB occurred in children, a finding different from preliminary data for adults.

Adolescent↗
PubMed1991

Ceftizoxime disposition in neonates and infants during the first six months of life.

The single-dose pharmacokinetics of ceftizoxime sodium were studied in 52 neonates and infants between 0.1 and 189 days of age. Subjects received ceftizoxime 25 or 50 mg/kg iv over 15-30 minutes. The drug was administered q8-12h for five days to permit tolerance evaluation on repetitive dosing. No differences were observed in ceftizoxime pharmacokinetic parameter estimates relative to dose. However, marked differences were observed in ceftizoxime pharmacokinetic characteristics relative to infant age; ceftizoxime half-life and mean residence time decreased, whereas body clearance increased with infant age. Ceftizoxime volume of distribution remained relatively constant over infant age. No adverse effects associated with ceftizoxime administration were observed. These data suggest that ceftizoxime 50 mg/kg q12h be used for infants less than or equal to 2 weeks of age (less than or equal to 40 weeks postconceptional age) and that 50 mg/kg q8h be administered for older infants.

Aging↗