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P Gal

Publications and source records attributed to P Gal.

At least 19 recordsLinked to original sources
PubMed2001

A multicenter evaluation of gentamicin therapy in the neonatal intensive care unit.

STUDY OBJECTIVE: To evaluate traditional nomogram (TN) versus individualized pharmacokinetic gentamicin dosing practices in neonatal intensive care units, focusing on achieving target therapeutic concentrations (peak > 8 microg/ml, trough < 2 microg/ml), number of dosing changes, number of concentrations obtained, and evidence of nephrotoxicity. DESIGN: Retrospective chart review. SETTING: Three neonatal intensive care units. PATIENTS: Three hundred nine infants prescribed gentamicin. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Sixty-seven percent of patients receiving pharmacokinetic dosing had initial peak concentrations of 8 microg/ml or greater compared with 7% of patients receiving TN dosing (p<0.001). Trough concentrations exceeding 2 microg/ml were reported in 23% of patients receiving TN dosing compared with 2% of pharmacokinetic-dosed patients (p<0.001). Forty-two percent and 6%, respectively, required dosage adjustments (p<0.01). The mean number of concentrations obtained per patient was 2.8 and 2.1, respectively (p<0.01). Neither group had evidence of gentamicin-related nephrotoxicity. CONCLUSION: Compared with TN dosing, administering gentamicin loading doses and performing initial pharmacokinetic analysis resulted in rapid attainment of desired concentrations and fewer dosage adjustments, and allowed for a decrease in the number of gentamicin concentrations.

Anti-Bacterial Agents↗
PubMed2000

Use of enoxaparin in a preterm infant.

OBJECTIVE: To describe the use of enoxaparin to treat suspected thrombosis in a preterm neonate. CASE DESCRIPTION: A 29-week-gestation white infant with a family history of protein S deficiency lost color and blood flow to the right hand several hours after removal of the umbilical artery catheter. Although normal color returned to all except the distal first, second, and third fingers after warming, Doppler flow showed a radial artery defect, indicating a lack of blood flow. Enoxaparin 1 mg/kg intravenously every eight hours was then started. Heparin concentrations measured via anti-Xa assay drawn four and eight hours after a dose were 0.78 and 0.39 units/mL, respectively. Pharmacokinetic parameters calculated from these concentrations using a one-compartment model were elimination half-life four hours, volume of distribution 0.13 L/kg, and clearance 0.022 L/kg/h. No adverse effects were noted. Blood flow eventually returned, leaving only the third fingertip chronically injured. DISCUSSION: Differences between the neonatal and adult hemostatic systems contribute to an increased risk of thromboembolic events and an altered sensitivity to heparin anticoagulation in the neonate. Although heparin is currently the anticoagulant of choice, it may produce several adverse effects, such as hemorrhage and thrombocytopenia, which may be avoided by use of low-molecular-weight heparins (LMWHs). However, despite the efficacy and improved safety profile of LMWHs in adults, data regarding their use in children and neonates are scarce. This case demonstrates that enoxaparin can be used safely and effectively in a preterm infant through appropriate monitoring of heparin concentrations to adjust dosages. A larger volume of distribution of enoxaparin was noted in this neonate than in adults. CONCLUSIONS: Enoxaparin 1 mg/kg intravenously every eight hours was used safely in this preterm infant with suspected thrombosis, suggesting that more than one dosing regimen may be appropriate in this population.

Anticoagulants↗
PubMed1999

Comparing the delivery of albuterol metered-dose inhaler via an adapter and spacer device in an in vitro infant ventilator lung model.

OBJECTIVE: To compare the delivery of an albuterol metered-dose inhaler (MDI) (Ventolin) via an Aerochamber (Monaghan) with an inline adapter (Medicomp Straight Swivel) in an in vitro infant lung model. METHODS: An in vitro infant lung model was modified to compare the delivery of albuterol MDI 10 inhalations via an Aerochamber with an inline adapter. The adapter and Aerochamber were placed at the endotracheal tube. A 1000 mL intravenous bag filled with 500 mL deionized water was attached to a 3.5 mm endotracheal tube (10 cm length). An Infant Bear Cub ventilator was used at the following settings: positive inspiratory pressure 20 cm H2O, intermittent mandatory ventilation 40 breaths/min, positive end expiratory pressure 4 cm H2O, and inspiratory time 0.5 second. Each device was run at least 10 times and assayed in duplicate by HPLC. An unpaired Student's t-test was used to analyze the statistical significance of the data. RESULTS: There was significantly greater delivery of albuterol with the Aerochamber (19.49 +/- 7.23 microg; 2.17% +/- 0.8%) as compared with an inline adapter (1.0625 +/- 1.36 microg; 0.12% +/- 0.15%) (p = 0.001). CONCLUSIONS: The Aerochamber provides a greater delivery of albuterol metered-dose inhalations to the lung than the inline adapter in an in vitro infant lung model.

Albuterol↗
PubMed1999

Evaluating the delivery of nebulized and metered-dose inhalers in an in vitro infant ventilator lung model.

OBJECTIVE: To evaluate drug delivery to the lungs of nebulized and metered-dose inhalers (MDIs) in an in vitro infant lung model. METHODS: An in vitro lung model was modified to study drug delivery. A 1000 mL intravenous bag filled with 500 mL deionized water was attached to a 3.5 mm (12 cm length) endotracheal tube. An inline Marquest Whisper Jet infant circuit nebulizer system delivered 2.5 mg/3 mL albuterol sulfate inhalation solution (Ventolin nebules) at a flow rate of 5 L/min. An Aerochamber (Monaghan) was placed at the endotracheal tube for the delivery of the MDIs. Albuterol MDI (Ventolin) 10 inhalations and beclomethasone MDI (Beclovent) 20 inhalations were delivered. A Servo 900C (Siemens-Elma) was used at the following ventilator settings: positive inspiratory pressure 30 cm H2O), intermittent mandatory ventilation 40 breaths/min, positive end expiratory pressure 4 cm H2O, inspiratory time 0.4 sec. Each formulation was run at least 10 times and assayed in duplicate by HPLC. An unpaired Student's t-test was used to analyze the statistical significance of the data. RESULTS: There was a significantly greater percentage of drug delivery with MDI albuterol (1.96 +/- 0.50) as compared with nebulized albuterol (1.26 +/- 0.37) (p = 0.002) or beclomethasone diproprionate (0.51 +/- 0.24) (p = 0.001). CONCLUSIONS: Albuterol MDI provides a more efficient delivery of drug to the lung as compared with nebulized albuterol and MDI beclomethasone diproprionate.

Albuterol↗
PubMed1998

Antiretroviral medication compliance in patients with AIDS.

The paradigm of AIDS patient care has evolved to that of a chronic disease that is manageable with combination antiretroviral therapy. Intermittent adherence to antiretroviral regimens, however, has been associated with the selection of HIV mutations, resulting in drug-resistant virus. Medication compliance has become a vital component in the care of HIV-infected patients. This study was designed to assess the degree of medication compliance with zidovudine (ZDV) over a 2-month period among a convenience sample of 23 ambulatory patients with HIV infection. Enrollment took place during February to March 1995, when monotherapy with ZDV was considered the standard of care. Medication compliance was assessed by three methods: patient self-report determined by questionnaire, pharmacy refill records from the 3 months immediately before entry in the study, and an electronic monitoring system (Medication Event Management Systems [MEMS], Aprex Corp., Fremont, CA), which records the date and time of each opening of the medication vials. MEMS was utilized among a subgroup of eight participants over a 2-month period. Despite greater than 95% (22 of 23) of the subjects reporting that they believed ZDV was life prolonging, a majority took < or = 75% of the prescribed doses of ZDV as identified by both refill and MEMS methods. The mean percentage compliance over a 2-month period of observation for MEMS and pharmacy refill record review methods was 66% and 78%, respectively (p = 0.294). Among the subgroup of eight in the MEMS evaluation, 88% reported taking their ZDV according to the directions, all of the time. These results demonstrate that reliance upon patient self-report of medication compliance is less accurate than MEMS or pharmacy refill records, and that reliance on self-reporting could lead to erroneous assumptions of the patient's true drug compliance. In addition, the study suggests that pharmacy refill records may provide a method of assessing compliance that is equivalent to MEMS but is less experimental, and can easily be followed and interpreted by pharmacists and other clinicians caring for patients infected with HIV. Most importantly, relatively poor compliance rates demonstrated by MEMS raises serious concern for widespread development of HIV resistance to the more complicated, multiple-drug regimens in present use.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Gentamicin pharmacokinetics in neonates with patent ductus arteriosus.

OBJECTIVES: To determine the effect of patent ductus arteriosus on the pharmacokinetics of gentamicin in neonates and to examine whether any particular pharmacokinetic parameter is of value as a marker of patent ductus arteriosus. DESIGN: Cohort study of neonates treated with gentamicin, according to a standard dosing protocol. SETTING: A 24-bed, Level III, neonatal intensive care unit. PATIENTS: Neonates treated with gentamicin at the time of admission to the neonatal intensive care unit, using a standard protocol, and who were < 36 wks of gestational age. INTERVENTIONS: All patients received a gentamicin loading dose, and had gentamicin concentrations measured at 2 and 12 hrs after this dose, in order to determine pharmacokinetic parameters and calculate the optimum maintenance dose. Those neonates subsequently diagnosed to have patent ductus arteriosus, based on clinical suspicion and echocardiographic confirmation, were compared with those neonates without clinically suspected patent ductus arteriosus. Gentamicin pharmacokinetic parameters were calculated using a one-compartment model. MEASUREMENTS AND MAIN RESULTS: A total of 322 courses of gentamicin were administered (patent ductus arteriosus, n = 106; control, n = 216). Gentamicin clearance was decreased in the patent ductus arteriosus group vs. the control group (40.02 vs. 44.73 mL/kg/hr; p < .0108). Volume of distribution was greater for patent ductus arteriosus patients (0.61 L/kg) than for controls (0.54 L/kg) (p < .0002). Also, volume of distribution was a useful marker for presence of patent ductus arteriosus, with a 92% specificity for patent ductus arteriosus. CONCLUSIONS: Gentamicin dosing should be altered in neonates with patent ductus arteriosus to reflect the impact of higher volume of distribution and lower clearance. When the gentamicin volume of distribution exceeds 0.7 L/kg, it may be of predictive value for the presence of patent ductus arteriosus.

Anti-Bacterial Agents↗
PubMed1997

Evaluation of a sparse sampling strategy for determining vancomycin pharmacokinetics in preterm neonates: application of optimal sampling theory.

OBJECTIVE: To use optimal sampling theory to determine the fewest vancomycin concentrations required and the appropriate sampling times to calculate vancomycin pharmacokinetic parameters in neonates. DESIGN: Unblinded evaluation in neonates with presumed sepsis. SETTING: Level 3 community-based neonatal intensive care unit. PATIENTS: Eleven neonates with presumed sepsis. INTERVENTIONS: Twelve courses of intravenous vancomycin 20 mg/kg were administered. Blood samples were collected 3 and 9 hours after initiation of a 1-hour infusion of the first dose. MEASUREMENTS AND MAIN RESULTS: A two-compartment model was fit to vancomycin concentrations using iterative two-stage analysis. Pharmacokinetic parameter estimates were used for determination of optimal sampling times for two-, three-, and four-sample strategies with subsequent generation of two-, three-, and four-sample concentration data for 100 cases. Relative performance of strategies was compared through calculation and comparison of D efficiency for the determined strategies. Bias (median percent error) and precision (median percent absolute error) of pharmacokinetic parameter estimates for each strategy in the 100 simulated cases were determined. CONCLUSIONS: For estimation of total clearance and volume in the central and peripheral compartments, all strategies performed similarly with no difference in efficiency or bias and precision of estimates. Our results suggest that for clinical evaluations two appropriately timed samples (0.5 h after a 1-h infusion, trough concentration) are adequate for estimation of vancomycin clearance in neonates.

Aminoglycosides↗
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

Ticarcillin-clavulanic acid pharmacokinetics in preterm neonates with presumed sepsis.

The objective of the reported study was to characterize the pharmacokinetics of ticarcillin and clavulanic acid in premature low-birth-weight (less than 2,200 g) neonates with presumed sepsis. Eleven infants received 12 courses of ticarcillin-clavulanic acid at 75 mg/kg of body weight intravenously every 12 h. Blood samples were collected at 0.5, 1.5, 4, and 8 h following the infusion of the initial dose. The concentrations of ticarcillin and clavulanic acid were determined by a microbiologic assay. Median (interpatient coefficients of variation) values for the volume of the central compartment, total steady-state volume, distributional clearance, total clearance, and terminal elimination half-life for ticarcillin were 0.030 liter/kg (21%), 0.26 liter/kg (48%), 0.41 liter/h/kg (47%), 0.047 liter/h/kg (47%), and 4.2 h (45%), respectively. For clavulanic acid the parameters were 0.28 liter/kg (32%), 0.36 liter/kg (34%), 11 liters/h/kg (36%), 0.12 liters/h/kg (72%), and 1.95 h (40%), respectively. Our results suggest that the current dosing recommendations of 75 mg/kg every 12 h risk subtherapeutic clavulanic acid concentrations and that 50 mg/kg every 6 h is a more rational dosing strategy.

Anti-Bacterial Agents↗
PubMed1994

The role of inhaled steroids in the treatment of bronchopulmonary dysplasia.

Bronchopulmonary dysplasia has been well described in premature infants requiring mechanical ventilation. Systemic steroids are one of many treatment modalities used in the management of these infants, but these agents have been associated with a number of adverse effects. Aerosolized therapy has been proposed as an alternative in order to minimize the systemic complications that occur with the parenteral route. The initial reports of inhaled steroids, although limited, have shown promising results with minimal side effects. This article addresses the mechanism of action, the role in therapy, and potential complications associated with the use of inhaled steroids in the treatment of bronchopulmonary dysplasia.

Administration, Inhalation↗
PubMed1993

Drug disposition in neonates with patent ductus arteriosus.

OBJECTIVE: To review the literature on the physiologic changes created by neonatal patent ductus arteriosus (PDA) and the potential impact on drug disposition in these infants. DATA SOURCES: An Index Medicus and bibliographic search of the English-language literature pertaining to neonatal PDA and drug usage in newborns. DATA SYNTHESIS: PDA in premature infants is associated with a variety of physiologic changes that could alter drug disposition. Perfusion of drug-elimination organs (i.e., liver and kidney) may be diminished, resulting in decreased drug elimination. Further, the general fluid overload state associated with PDA may result in larger volumes of distribution (Vd), and dilutional effects for many drugs. Drug absorption, Vd, tissue penetration, and clearance may be affected by the physiologic changes incurred by a PDA. Although the pharmacokinetics of several categories of therapeutic agents may be affected by a PDA, disposition changes with the aminoglycosides and indomethacin have been the best documented. The most reliable pharmacokinetic change appears to be related to drug Vd. The interpretation of many of these studies is confounded by a potential drug interaction with the concurrent administration of indomethacin for PDA closure. CONCLUSIONS: Close therapeutic drug monitoring is indicated in newborns with PDAs as abrupt changes in drug disposition can occur with PDA closure. PDA-induced changes in specific pharmacokinetic parameters of agents such as the aminoglycosides, indomethacin, and perhaps vancomycin may prove to be a valuable diagnostic adjunct for the identification of babies with undiagnosed PDA. More research into this pharmacophysiologic aspect of pharmacokinetics is warranted.

Absorption↗
PubMed1993

Rapid determination of maintenance heparin infusion rates with the use of non-steady-state heparin concentrations.

OBJECTIVE: To compare heparin dosage adjustment using only activated partial thromboplastin time (APTT) with a method using non-steady-state heparin concentrations (HCs) to rapidly achieve and maintain an APTT ratio greater than or equal to 1.5 times baseline throughout the first 24 hours of therapy. DESIGN: Randomized, blind, parallel comparison of an empiric dosing method based only on APTT with a dosing method based on the calculation of heparin clearance using non-steady-state HCs. SETTING: A private community teaching hospital. The patient, physician, nurses, and investigators were blinded to the dosing method. Only the clinical staff pharmacist, who received the consult and made all dosage adjustments, was not blinded. PATIENTS: All patients requiring heparin for the treatment of thromboembolic disease were evaluated for potential inclusion in the study. Patients were enrolled in the study if they had a clinical diagnosis of deep venous thrombosis confirmed by objective means such as venography or ultrasonography. Patients were excluded if they had active bleeding, platelet dysfunction, thrombocytopenia, severe hepatic disease (total bilirubin > 25.7 mumol/L), renal disease, or evidence of stroke. Patients were also excluded if they were receiving heparin prior to enrollment. MAIN OUTCOME MEASURE: Maintenance of an APTT ratio greater than or equal to 1.5 times baseline throughout the first 24 hours of heparin therapy. RESULTS: Thirty-four patients were enrolled in the study; 17 in each group. The groups were not significantly different with regard to gender, age, baseline APTT, or mean loading dose (p > 0.5). Mean initial infusion rates for the control and HC groups were 1042 +/- 194 and 1071 +/- 143 units/h, respectively (p > 0.5). After the first rate adjustment at 4 hours, the difference achieved significance at 1032 +/- 232 and 1367 +/- 317 units/h for the control and HC groups, respectively (p < 0.01). At 12 hours, 18.8 percent of the patients in the control group were subtherapeutic; by 24 hours, 33.3 percent were subtherapeutic. No patients became subtherapeutic in the HCs group during the first 24 hours. CONCLUSIONS: This study demonstrates that, in contrast to standard heparin dosing methods, the use of non-steady-state HCs allows patients with deep venous thrombosis to rapidly achieve and maintain therapeutic APTT ratios throughout the critical first 24 hours of therapy.

Female↗