Search PubMed⌕ Search

Biomedical subjects

J L Blumer

Publications and source records attributed to J L Blumer.

At least 19 recordsLinked to original sources
PubMed1999

Paroxetine pharmacokinetics in depressed children and adolescents.

OBJECTIVE: To describe the pharmacokinetics and safety of paroxetine in children and adolescents and to explore the role of genetic polymorphisms in paroxetine pharmacokinetics. METHOD: Thirty depressed youths were enrolled. Samples for phenotyping with respect to cytochrome P450 2D6 (CYP2D6) and catechol-O-methyltransferase were collected. A single 10-mg dose of paroxetine was then administered followed by 5 days of blood and urine collection for pharmacokinetic analyses. Subjects subsequently received open treatment for 8 weeks, and weekly blood samples were obtained for plasma concentration measurements. RESULTS: There was tremendous interindividual variability in paroxetine disposition. The mean half-life of paroxetine was 11.1 +/- 5.2 (SD) hours. The average clearance was 88.7 +/- 66.4 mL/min/kg. The mean area under the plasma drug concentration curve was 0.09 +/- 0.10 microgram/mL.hr. Within-subject variability of plasma paroxetine concentrations was generally not significant. Clearance and fractional urinary excretion of paroxetine were found to correlate with CYP2D6 activity. Two subjects developed hypomania necessitating drug discontinuation. No clinically significant changes in any safety assessments were noted. CONCLUSIONS: Paroxetine is more rapidly cleared in youths than adults and may be given once daily in this population. Short-term treatment with paroxetine appears safe and well tolerated in this relatively small sample of pediatric patients.

Adolescent↗
PubMed1998

Pharmacokinetics of metoclopramide in neonates.

Despite its wide use as a prokinetic agent in neonates and infants with gastroesophageal reflux (GER), the pharmacokinetics of metoclopramide have not been characterized in this pediatric subpopulation. A single-dose pharmacokinetic study of oral metoclopramide (0.1 to 0.15 mg/kg) was performed in 10 fasted premature infants (weight 1.1 to 3.2 kg) ranging from 31 to 40 weeks postconceptional age. Metoclopramide was quantitated from repeated blood samples (n = 9 over 24 hours) by high-performance liquid chromatography. A one-compartment open model with first-order absorption best described the plasma concentration-time data. No correlations were observed between gestational, postnatal, or postconceptional age and any of the pharmacokinetic parameters studied. Comparison of the pharmacokinetic parameters from the study cohort and those reported previously from a similar study of older infants revealed no statistically significant differences. However, a prolonged apparent plasma clearance (Cl/F) of metoclopramide was observed in 30% of the infants studied, and the mean Cl/F and apparent steady-state volume of distribution (Vdss/F) were approximately 1.4- and 2.1-fold higher, respectively, than values reported in previous studies of metoclopramide disposition in adults. These data suggest that metoclopramide pharmacokinetics may exhibit a developmental dependency. Thus, a metoclopramide dose of 0.15 mg/kg given orally every 6 hours is recommended for the initiation of prokinetic therapy with this agent in infants who are < or = 31 weeks postconceptional age.

Administration, Oral↗
PubMed1998

The antipsychotics. A pediatric perspective.

As can be discerned from this article, antipsychotics are commonly prescribed, and they are not used to treat only psychosis. Although some data support the use of typical antipsychotics in pediatric patients with a variety of psychiatric syndromes, concerns about the safety and tolerability of these agents often complicated their use and probably even interfered with case identification. A fundamentally new group of medications, the atypicals, have now become available and may not only have improved tolerability but also may have greater ability to reduce some target symptoms. Because of their superior side-effect profile in adults, some of these atypical treatments probably will be commonly prescribed despite a relative paucity of data about their use in the young. Moreover, although frequently prescribed in this age group, the overall prescription rate for antipsychotics will probably increase because of the putative improved safety profile of the newer agents. However, it is possible that serious side effects, such as tardive dyskinesia or neuroleptic malignant syndrome, may occur with these atypical agents. For this reason, the enthusiasm for prescribing these newer treatments should be tempered with the understanding that these agents, although they may in some ways be superior to their predecessors, still possess the potential for significant adverse events. Four atypical antipsychotics are currently marketed in the United States (see Table 2). One additional agent, ziprasodone, is undergoing clinical investigation. Ziprasodone has been shown to be superior to placebo in adults suffering from schizophrenia. Ziprasodone will probably be marketed in the United States in the near future. Whether all of these atypical drugs will have a place in the clinical armamentarium of the pediatric psychopharmacologist remains to be determined. Because the receptor binding profile of the atypical agents differ, it is not possible to assume that what is true for one of these agents is true for the others. Although results from most preliminary studies with atypical antipsychotics indicate that these are promising agents for pediatric patients, further research is needed to define just how these medications may be most judiciously used.

Adolescent↗
PubMed1998

Pharmacokinetics and pharmacodynamics of new and old antimicrobial agents for acute otitis media.

Selection of appropriate antibiotic treatment for children with acute otitis media (AOM) is challenging. Although the diagnosis is relatively easy for experienced clinicians, the distinction between AOM and otitis media with effusion is often more subtle. In general therapy is empiric and the pathogen causing disease in a given patient remains unknown. However, this situation is made even more difficult by the dynamic nature of the pathogenesis of AOM. Both the proportion of patients infected with one of the three primary pathogens, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, and the antimicrobial susceptibility patterns of these pathogens are changing. Currently there are 16 antibiotics labeled for use in AOM. Only 2 are reliably effective against penicillin-resistant pneumococcus: high dose amoxicillin (80 to 100 mg/kg/day) and im ceftriaxone. Among the others all are beta-lactamase-stable and have proven clinical effectiveness in AOM patients infected with H. influenzae or M. catarrhalis. Even with the high spontaneous resolution rate reported for AOM, antimicrobial therapy remains the standard of care in the United States. Recognition of the fundamental determinants of effective therapy should permit rational antibiotic selection for each patient.

Acute Disease↗
PubMed1998

Clinical pharmacology of midazolam in infants and children.

Midazolam is a parenteral benzodiazepine with sedative, amnesic, anxiolytic, muscle relaxant and anticonvulsant properties. The drug exerts its clinical effect by binding to a receptor complex which facilitates the action of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Midazolam has a faster onset and shorter duration of action than other benzodiazepines such as diazepam and lorazepam. The most serious adverse events associated with midazolam in children include hypoventilation, decreased oxygen saturation, apnoea and hypotension. It is water soluble in the commercially prepared formulation but becomes lipid soluble at physiological pH and can then cross the blood brain barrier. It is metabolised in the liver by the cytochrome P450 system, and its chief metabolite is 1-hydroxymethyl midazolam. The latter is conjugated to the glucuronide form, and it has only minimal biological activity. Midazolam is excreted primarily by the kidney. Its half-life in children over 12 months is reported to be 0.8 to 1.8 hours, with a clearance of 4.7 to 19.7 ml/min/kg. Doses given to children must be calculated on a mg/kg basis. For children 6 months to 5 years of age the initial dose is 0.05 to 0.1 mg/kg. A total dose up to 0.6 mg/kg titrated slowly may be necessary to achieve the desired endpoint. For children 6 to 12 years of age the initial dose is 0.025 to 0.05 mg/kg with a total dose up to 0.4 mg/kg to achieve the desired end-point.

Anti-Anxiety Agents↗
PubMed1997

Evaluation of predictors of weaning from mechanical ventilation in pediatric patients.

Objective criteria for ending mechanical ventilation have not been established for infants and children. A recent study in adult patients developed two new indexes, the Rapid Shallow Breathing Index (RSB) and the CROP Index for predicting success or failure of extubation. We decided to evaluate the applicability of these indices to intubated, mechanically ventilated pediatric patients. For this evaluation the indices were adapted to the physiology of infants and children. A pneumotachograph was used to measure spontaneous tidal volume, respiratory rate and dynamic compliance. The tidal volume and the dynamic compliance were corrected for the patient's body weight. Based on the data collected a cutoff value for each index was determined. Of 47 sets of patient data, 38 (81%) were collected during successful extubations, 9 (19%) during failed extubations. A modified CROP index value of > or = 0.1 ml x mmHg/bpm/kg and a modified RSB index value of < or = 11 bpm/mlkg were identified as predictive of successful extubation. The modified CROP cutoff value produced a sensitivity and specificity of 1.0; respective values for the modified RSB cutoff value are 0.79 and 0.78. Cutoff values of > or = 0.1 and < or = 11 for the modified CROP index and RSB index, respectively, appear to be predictive of successful extubation in the pediatric population. Our data identifies the modified CROP index as a superior discriminator between successful and unsuccessful extubation.

Adolescent↗
PubMed1997

Advances in the therapy for sepsis in children.

Sepsis remains a major clinical problem in children, with a high mortality rate. Recent discoveries have identified the major cytokines involved in sepsis and several anticytokine strategies have been used in clinical trials. Antiendotoxin, anticytokine, and even steroid therapy have been studied in humans, with limited success. Several of the clinical trials of immunotherapy in sepsis are reviewed, and the inherent pitfalls in the varied clinical approaches investigated are analyzed.

Antibodies, Monoclonal↗
PubMed1997

The pharmacokinetics of teicoplanin in infants and children.

The pharmacokinetics of teicoplanin were assessed after a single dose and under multidose conditions in 12 infants and children. Study patients ranged in age from 2.4 to 11 years. Each patient received teicoplanin 6 mg/kg body weight given intravenously over 20-30 min, once daily for five consecutive days. Multiple timed blood and urine samples were obtained over the 6 day sampling period and were analysed for teicoplanin by both microbiological assay and HPLC. Three-compartment pharmacokinetic analysis was used to describe the drug's disposition characteristics. Peak and 24 h trough serum teicoplanin concentrations averaged 39.3 and 1.8 mg/L after the first dose with little accumulation observed after 5 days of therapy. Teicoplanin disposition was variable; V(d)ss ranged from 0.31 to 0.68 L/kg, t(1/2)gamma from 6.5 to 18.1 h and CI from 29 to 51 mL/h/kg. A substantial amount of the administered drug distributed rapidly to the largest, third compartment, with egress approximately four-fold slower than ingress. The majority of the drug was excreted unchanged in the urine. Teicoplanin administration was well tolerated by all study subjects. Using the teicoplanin pharmacokinetic data derived in our study, a dose of teicoplanin 8 mg/kg body weight administered every 12 h should achieve target serum trough concentrations averaging 11 mg/L in children. Higher doses, e.g. 15 mg teicoplanin/kg administered every 12 h, may be needed for the treatment of deep-seated staphylococcal infections and/or endocarditis.

Anti-Bacterial Agents↗
PubMed1997

Alterations in dopamine clearance and catechol-O-methyltransferase activity by dopamine infusions in children.

OBJECTIVE: To determine the role of catechol-O-methyltransferase (COMT) in the biodisposition of pharmacologic concentrations of dopamine. DESIGN: The study was an open-label dose escalation trial in which dopamine was employed as the sole exogenous catecholamine. The dosage was adjusted to achieve improvements in cardiac output or to augment renal function. SETTING: A 16-bed pediatric intensive care unit serving both medical and surgical patients. PATIENTS: The study was performed using 14 dopamine-treated and five untreated control patients. Children ranged in age from 16 days to 12 yrs; five of the treated patients and two of the untreated controls were female. All but one of the study patients were enrolled within 24 hrs of palliative or corrective surgery for congenital heart disease. Control patients had noncardiac surgical procedures. Both treated and control groups were similar with respect to severity of illness, as judged by Therapeutic Intervention Scoring System score. INTERVENTIONS: All treated patients received dopamine as a continuous intravenous infusion. Infusion rates were determined by caregivers and ranged from 3.0 to 20 micrograms/kg/min. MEASUREMENTS AND MAIN RESULTS: Serial, timed blood samples were obtained from patients and control subjects for the determination of plasma dopamine concentrations and for the determination of mononuclear cell COMT activity. Measured rates of dopamine infusion (3.0 to 18.3 micrograms/kg/min) were consistently less than the nominal rates (3.0 to 20.0 micrograms/kg/min) of infusion (p < .0001) due in part to calculations based on the hydrochloride salt rather than dopamine base. At similar steady-state infusion rates, plasma dopamine concentrations varied over a four-fold range, with steady-state concentrations at even the lowest infusion rate exceeding endogenous concentrations by at least ten-fold. Variations in steady-state plasma dopamine concentration reflected large age-associated variations in dopamine clearance, which was found to be saturable at concentrations of > 200 ng/mL. Mononuclear cell COMT activity was assessed simultaneously in these patients. Baseline COMT activity varied over a six-fold range and was unrelated to dopamine clearance or patient age. COMT activity increased two- to six-fold in dopamine-treated patients with plasma steady-state dopamine concentrations of > 100 ng/mL. CONCLUSIONS: These data demonstrate marked age and concentration-dependent differences in dopamine clearance that account for large interindividual differences in the steady-state plasma dopamine concentrations in patients receiving similar infusion rates. While concomitant variability in COMT activity is observed, the lack of correlation between dopamine clearance and COMT activity suggests that COMT is not rate-limiting for the clearance of exogenously administered dopamine.

Catechol O-Methyltransferase↗
PubMed1997

Colonization with antibiotic-resistant gram-negative organisms in a pediatric intensive care unit.

OBJECTIVE: To measure the prevalence of colonization with antibiotic-resistant Gram-negative organisms and its association with potential risk factors, including antibiotic exposure, in a pediatric intensive care unit (ICU). DESIGN: Prospective, observational study. SETTING: A 16-bed tertiary care pediatric ICU. PATIENTS: All children admitted to the pediatric ICU for > 24 hrs over a 5-month period. MEASUREMENTS AND MAIN RESULTS: Two hundred ninety-six patients, approximately half of all patients admitted to the ICU, were enrolled in the study; 236 patients had sufficient data collected for analysis and were prospectively examined for nasopharyngeal and gastrointestinal colonization by antibiotic-resistant Gram-negative organisms (ceftazidime minimal inhibitory concentration of > 16 micrograms/mL, or tobramycin minimal inhibitory concentration > 8 micrograms/mL). Association between colonization and potential predisposing factors including demographics, diagnosis, Pediatric Risk of Mortality (PRISM) score, invasive instrumentation, and prior ICU antibiotic exposure was assessed. More than 20% of patients were found to be colonized with an antibiotic-resistant Gram-negative organism. Examination of the timing of colonization indicated that more than half were identified within 72 hrs of admision. Colonization was associated by unadjusted analysis to prior ICU antibiotic exposure, as well as by factors associated with the severity of illness (PRISM score and invasive instrumentation) and young age. However, when the independence of these factors was tested by logistic regression, prior antibiotic exposure was no longer associated with resistant organism colonization. CONCLUSIONS: These data suggest that antibiotic-resistant Gram-negative organisms are a significant risk to intensively III children and that in many instances, they are imported into the unit or rapidly acquired from environmental reservoirs. Since risk factors for colonization are multiple, policies confined to antibiotic utilization within the ICU may have fixed, and possibly limited, benefit in their control.

Carrier State↗
PubMed1997

Exercise training decreases the growth hormone (GH) response to acute constant-load exercise.

To assess the influence of exercise training on the growth hormone (GH) response to acute exercise, six untrained males completed a 20-min, high-intensity, constant-load exercise test prior to and after 3 and 6 wk of training (the absolute power output (PO) during each test remained constant x PO = 182.5 +/- 29.5 W). Training increased (pre- vs post-training) oxygen uptake (VO2) at lactate threshold (1.57 +/- 0.33 L.min-1 vs 1.97 +/- 0.24 L.min-1 P < or = 0.05). VO2 at 2.5 mM blood lactate concentration ([HLa]) (1.83 +/- 0.38 L.min-1 vs 2.33 +/- 0.38 L.min-1, P < or = 0.05), and VO2peak (3.15 +/- 0.54 L.min-1 vs 3.41 +/- 0.47 L.min-1, P < or = 0.05). Power output at the lactate threshold (PO-LT) increased with training from 103 +/- 28 to 132 +/- 23W (P < or = 0.05). Integrated GH concentration (20 min exercise + 45 min recovery) (microgram.L-1 x min) after 3 wk (138 +/- 106) and 6 wk (130 +/- 145) were significantly lower (P < or = 0.05) than pre-training (238 +/- 145). Plasma epinephrine and norepinephrine responses to training were similar to the GH response (EPI-pre-training = 2447 +/- 1110; week 3 = 1046 +/- 144; week 6 = 955 +/- 322 pmol.L-1; P < or = 0.05; NE pre-training = 23.0 +/- 5.2; week 3 = 13.4 +/- 4.8; week 6 = 12.1 +/- 6.8 nmol.L-1; P < or = 0.05). These data indicate that the GH and catecholamine response to a constant-load exercise stimulus are reduced within the first 3 wk of exercise training and support the hypothesis that a critical threshold of exercise intensity must be reached to stimulate GH release.

Adult↗
PubMed1997

Pharmacokinetics of intravenously and intramuscularly administered cefepime in infants and children.

The pharmacokinetic characteristics of cefepime were determined after first dose (n = 35) and again under steady-state conditions (n = 31) with a group of 37 infants and children. In eight subjects, a cefepime dose given by intramuscular injection was substituted for an intravenous dose, and disposition characteristics were studied again. Study subjects ranged in age from 2.1 months to 16.4 years, and all had normal renal function. Each patient received 50 mg of cefepime/kg of body weight intravenously every 8 h, up to a total maximum individual dose of 2 g. With the exception of one study patient who received a single cefepime dose for surgical prophylaxis, the patients received cefepime for 2 to 13 days. Elimination half-life (t1/2), steady-state volume of distribution, total body clearance, and renal clearance after first dose administration averaged 1.7 h, 0.35 liter/kg, and 3.1 and 1.9 ml/min/kg, respectively. Although cefepime t1/2 and mean residence time (MRT) were slightly longer for subjects <6 months of age than for older subjects, no differences in cefepime disposition characteristics between first dose and steady-state evaluations were observed. t1/2 (1.8 versus 1.9 h) and MRT (2.3 versus 3.2 h) were slightly prolonged after intramuscular administration, reflecting the influence of absorption from the intramuscular injection site on cefepime elimination. Bioavailability after intramuscular administration averaged 82% (range, 61 to 124%). Fifty-seven percent of the first dose and 88.9% of the last dose were recovered as unchanged drug in urine over the 8- and 24-h sampling periods, respectively. These pharmacokinetic data support a single cefepime dosing strategy for patients > or =2 months of age. The integration of the cefepime pharmacokinetic data generated in our study with the MICs for important pathogens responsible for infections in infants and children supports the administration of a dose of 50 mg of cefepime/kg every 12 h for patients > or =2 months of age to treat infections caused by pathogens for which cefepime MICs are < or =8 mg/liter.

Adolescent↗
PubMed1997

Ketamine-midazolam versus meperidine-midazolam for painful procedures in pediatric oncology patients.

PURPOSE: To compare the efficacy, characteristics of onset/recovery, and safety of ketamine/atropine/midazolam with meperidine/midazolam used as premedication for painful procedures in children with cancer. METHODS: A randomized, double-blind crossover trial for two successive painful procedures (bone marrow aspiration or biopsy, lumbar puncture, or combined procedures) was performed at a referral-based pediatric hematology-oncology clinic and associated inpatient service of a university teaching hospital. Twenty-two children, aged 24 to 178 months, were enrolled and 18 (81.8%) completed the double-blind, crossover trial. Each child received intravenous premedication with either meperidine 2 mg/kg and midazolam 0.1 mg/kg (MM) or atropine 0.01 mg/kg, midazolam 0.05 mg/kg, and ketamine 1.5 mg/kg (KM) on one occasion followed by the alternative regimen on a second occasion. The initial premedication regimen was chosen by random assignment. RESULTS: Efficacy was assessed by a trained observer using the Observational Scale of Behavioral Distress-Revised (OSBD-R). Operator, nurse, parent, and patient opinions of efficacy were recorded on a visual analog scale (VAS). Side effects were monitored by pulse oximetry, nasal end-tidal capnography, and serial blood pressure measurements. Use of KM resulted in significantly less procedural distress than MM (1.37 +/- 2.20 v 7.04 +/- 8.06 OSBD-R units; P < .05). Both operators and nurses rated KM more effective than MM. KM use was associated with earlier readiness for the procedure (19.2 v 24.0 minutes) and more rapid recovery (39.3 v 74.6 minutes for removal of monitoring devices and 58.5 v 87.1 minutes for discharge). Procedures undertaken after ketamine sedation were associated with fewer side effects than observed with MM sedation (hypoxia, 17.7% v 82.4%; hypotension, 16.6% v 55.6%; reduced respiratory rate, 0% v 38.9%). The incidence of emergence reactions or behavioral abnormalities within 24 hours postprocedure was similar in both treatment groups. At 7 days postprocedure, no child had persistent behavioral abnormalities and all children had amnesia for the procedure. Parents and children expressed a preference for KM over MM in 12 of 18 cases (P < .05). CONCLUSION: A premedication regimen of KM produced superior sedation with a faster onset and recovery and fewer side effects than a MM combination.

Anesthetics↗