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Biomedical subjects

L L Dupuis

Publications and source records attributed to L L Dupuis.

At least 19 recordsLinked to original sources
PubMed2005

A pilot study of ondansetron plus metopimazine vs. ondansetron monotherapy in children receiving highly emetogenic chemotherapy: a Bayesian randomized serial N-of-1 trials design.

GOALS OF WORK: Chemotherapy-induced nausea and vomiting is problematic in paediatric brain tumour treatment protocols which often discourage the use of corticosteroids as anti-emetics. The dopamine receptor antagonist, metopimazine, is an effective anti-emetic in combination with ondansetron in adults. The present study was designed to assess its efficacy in children with cancer, a group in which it has not been studied previously. PATIENTS AND METHODS: We conducted a series of randomized, multiple-crossover, double-blind, placebo-controlled N-of-1 trials comparing ondansetron/metopimazine with ondansetron monotherapy in children with brain tumours receiving highly emetogenic therapy and combined the individual results using Bayesian statistical modeling. MAIN RESULTS: Ten of twelve enrolled patients completed at least one chemotherapy cycle on study (median=2.5 cycles, range 1-11). Two patients were unable to complete any cycles, and a further three patients withdrew from the study prior to completing all cycles because of an inability to tolerate the taste of the study drug. Combination therapy increased the proportion of days during which patients had no emesis (overall odds ratio=1.52, 95% credible region=0.32-6.40, probability of odds ratio>1=72%), decreased the number of emetic episodes per day (overall rate ratio=0.67, 95% credible region=0.15-3.14, probability of rate ratio<1=75%) and decreased parents' ratings of their child's distress. The drug was more effective during the delayed chemotherapy phase than the acute phase. No adverse events were attributed to metopimazine. CONCLUSIONS: Based on this pilot study, we believe that the high likelihood that metopimazine is an effective adjunct to ondansetron monotherapy suggests that this combination therapy is worthy of further study in children receiving emetogenic chemotherapy.

Antiemetics↗
PubMed2002

Outcomes of antiemetic prophylaxis in children undergoing bone marrow transplantation.

A prospective survey of the control of acute and delayed antineoplastic and radiation-induced nausea and vomiting was undertaken in children undergoing bone marrow transplantation (BMT) at The Hospital for Sick Children. Prior administration of antineoplastic agents or irradiation, presence of anticipatory nausea or vomiting prior to starting the conditioning regimen, antiemetic use within 24 h of conditioning, the prescribed antineoplastic and/or radiation ablative regimen, and prescribed antiemetic regimens were recorded. Emetic episodes, dietary intake, administration of conditioning agents and antiemetics, and adverse effects were monitored on each day of the conditioning regimen and for 96 h thereafter. Children older than 3 years of age assessed their nausea on each study day. Twenty-five children were followed for 258 patient days. Children did not vomit or retch on 73% and 43% of patient days, in the acute and delayed phases, respectively. Nausea data were evaluable for 21 children on 200 patient days. Nausea was absent on 55% and 26% of patient days in the acute and delayed phases, respectively. Five children never had an emetic episode during the entire study period. One child was completely free from nausea and vomiting throughout the study period. Antineoplastic and radiation-induced nausea and vomiting can be successfully prevented in the majority of children undergoing BMT. However, effective treatment strategies must be developed in the event of antiemetic failure and for effective prophylaxis in children who cannot tolerate dexamethasone.

Adolescent↗
PubMed2001

Delayed nausea and vomiting in children receiving antineoplastics.

BACKGROUND: The nature and prevalence of delayed antineoplastic-induced nausea and vomiting have not been well-described in children. This study describes the extent of delayed nausea and vomiting in children receiving antineoplastic agents as well as the drug therapies initiated in an attempt to prevent or manage it. PROCEDURE: All children receiving antineoplastics were eligible for study entry. The date and time of each emetic episode were recorded on each day antineoplastics were given and for 3 days thereafter. Nausea was self-assessed daily by children who were older than 3 years and were not developmentally delayed. Diet was also assessed daily. The emetic response, median nausea rating and median diet achieved were described. RESULTS: The emetic response of 124 children who received 174 antineoplastic cycles was evaluated. Most cycles (137/174;79%) were not associated with delayed vomiting. Cycles which included cisplatin, carboplatin, or cyclophosphamide; involved antineoplastic therapy given over 2 or more consecutive days; or were accompanied by vomiting during the acute phase were associated with a significantly higher incidence of delayed vomiting. Moderate to severe nausea was reported on 58% (267/459) of study days. No antiemetics were given on most study days (412/522;79%); nevertheless, most of the study days (381/412;93%) which were unaccompanied by antiemetic support during the delayed phase were completely free from vomiting. Antiemetics were most often given as single agents (ondansetron: 54 study days; dimenhydrinate: 17 study days; dexamethasone: 6 study days). Diet was largely unaffected during the study period. CONCLUSIONS: Antineoplastic-induced delayed nausea and vomiting may be less prevalent in children than in adults. Routine antiemetic administration during the delayed phase may not be warranted in all patients. Med Pediatr Oncol 2001;37:115-121.

Adolescent↗
PubMed2000

Retrospective appraisal of busulfan dose adjustment in children.

This report describes and critically appraises our experience with busulfan dose adjustment in children undergoing bone marrow transplant between April 1997 and March 1999. All children received an initial busulfan dose of 40 mg/m2 p.o. or by nasogastric tube. Whole blood samples were obtained 1, 1.5 and 6 h later and analyzed for busulfan content by gas chromatography with electron capture detection. The area under the whole blood busulfan concentration vs time curve (AUC) and an individualized dose which would achieve an AUC of 1300 microM/min were calculated. Mean and median busulfan doses were calculated using actual, ideal and effective body weight and stratified according to age. The relationship between the busulfan concentration at hour 6 and AUC was determined using linear regression. Thirty-nine courses of busulfan were evaluated in 38 patients. A change from the initial busulfan dose was required to achieve the target AUC in 34 courses (87%). Most children >1 to 5 years old required dose increments while most children >5 years old required dose reductions. Obesity did not significantly affect busulfan dose requirements. Busulfan concentrations at 6 h only weakly predicted the AUC achieved (r2 = 0.496; P = 0.001). Based on these findings, we recommend that the initial busulfan dose be assigned according to patient age and actual body weight. We also recommend that busulfan AUC be calculated for children using a four-sample (1, 1.5, 4 and 6 h) limited sampling technique.

Adolescent↗
PubMed1997

Stability of propafenone hydrochloride in i.v. solutions.

The stability of propafenone hydrochloride in i.v. solutions was studied. Solutions of propafenone hydrochloride 2, 1, and 0.5 mg/mL in 5% dextrose injection and in 5% dextrose and 0.2% sodium chloride injection were prepared. Portions of each type of solution were transferred to 10-mL polypropylene syringes and to 150-mL polyvinyl chloride (PVC) bags. Syringes and bags were stored at 20.5-22.5 degrees C under fluorescent light. Two 0.5-mL samples were drawn from each container at 0, 6, 12, 24, 36, and 48 hours and frozen in polystyrene tubes at -20 degrees C until assayed. Propafenone concentrations were determined by high-performance liquid chromatography. All samples of propafenone hydrochloride 2 mg/mL in 5% dextrose and 0.2% sodium chloride injection taken from PVC bags precipitated when thawed. For the remaining solutions, the mean decrease from the initial concentration was < 10% regardless of diluent, container type, and initial concentration. Propafenone hydrochloride 1 and 0.5 mg/mL in 5% dextrose injection or in 5% dextrose and 0.2% sodium chloride injection was stable for 48 hours at 20.5-22.5 degrees C when stored in polypropylene syringes or PVC bags. Propafenone hydrochloride 2 mg/mL in 5% dextrose injection was stable for 48 hours when stored in syringes or bags, but in 5% dextrose and 0.2% sodium chloride injection was stable in syringes only.

Anti-Arrhythmia Agents↗
PubMed1995

Influence of food on the bioavailability of oral methotrexate in children.

OBJECTIVE: To determine the bioavailability of oral methotrexate (MTX) in patients with juvenile rheumatoid arthritis in the fasting and fed states. METHODS: Each patient randomly received their usual weekly MTX dose either orally (po) after an overnight fast, po immediately after a breakfast of their choice, or intravenously (iv) on 3 consecutive weeks. Blood samples were taken at 0, 0.5, 1, 1.5, 2, 3, 4, and 6 h after po and 0, 0.08, 0.25, 0.5, 1, 1.5, 2, 3, 4, and 6 h after iv administration. RESULTS: Fourteen patients (10 female) aged 2.8 to 15.1 yrs completed the study; the results of 13 patients were evaluable. The mean elimination rate constant was 0.27 +/- 0.065, 0.26 +/- 0.067, and 0.25 +/- 0.11 h-1 after po fasting, po fed, and iv administration, respectively. The total area under the serum concentration vs time curve was 1.87 +/- 0.83, 1.50 +/- 0.51, and 1.85 +/- 0.80 mumol/l.h after po fasting, po fed, and iv administration, respectively. The maximum serum MTX concentration (Cmax) was 0.65 +/- 0.33 and 0.39 +/- 0.18 mumol/l after po fasting and po fed administration, respectively (p = 0.0022). The time to Cmax was 0.94 +/- 0.40 and 1.32 +/- 0.68 h after po fasting and po fed administration, respectively (p = 0.1464). The bioavailability of oral MTX while fasting was 1.1 +/- 0.51, while that after a meal was 0.88 +/- 0.35 (p = 0.0211). CONCLUSION: These data indicate greater oral bioavailability of MTX in the fasting state. We recommend that children receive MTX on an empty stomach.

Administration, Oral↗
PubMed1990

Methotrexate-nonsteroidal antiinflammatory drug interaction in children with arthritis.

In order to assess the interaction between methotrexate (MTX) and nonsteroidal antiinflammatory drugs (NSAID), we studied the pharmacokinetics of oral MTX alone and in the presence of the usually prescribed NSAID in 7 children with chronic arthritis. The NSAID studied included tolmetin, indomethacin, naproxen, and aspirin. Six patients were treated with multiple NSAID. The mean MTX elimination half-life was prolonged when NSAID were coadministered (1.7 +/- 0.5 vs 1.2 +/- 0.1 h; p = 0.03). However, neither the apparent MTX clearance (CI) (10.6 +/- 5.5 vs 13.1 +/- 3.5 l/h; p = 0.19), the area under the serum MTX concentration-time curve (Auc) (2.1 +/- 1.0 vs 1.5 +/- 0.6 mumol/l/h; p = 0.08) or the apparent volume of distribution (Vd) (23.0 +/- 6.2 vs 21.9 +/- 6.4 l; p = 0.53) was significantly altered by the administration of NSAID. Although the differences between the mean Cl and Auc were not statistically significant, a wide variation in the impact of NSAID on MTX Cl was observed. In 6 of 7 patients, the Auc increased during NSAID administration from 19 to 140%. This degree of increase may be clinically significant in some individuals. It is consequently recommended to closely monitor patients who are receiving MTX and NSAID for MTX toxicity until these results can be verified in a larger population.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1990

Pharmacist intervention in prescribing of cefuroxime for pediatric patients.

A targeted drug review of cefuroxime use in pediatric patients is described. Because of a 65% increase in cefuroxime costs over one year, pharmacists assessed the appropriateness of cefuroxime therapy from October 13 to December 20, 1987. This assessment was done within 48 hours after the prescription was written and again after 72 hours of cefuroxime therapy, when bacteriology and susceptibility data were available. When a drug order was inappropriate, a pharmacist intervened with the prescribing physician. For comparison, data collection forms were completed for patients who had received cefuroxime before and after the study period. Before the study period, 42% of the cefuroxime orders were inappropriate with respect to dosage or indication at the time of the initial order; this rate fell to 26% during the study period and increased to 33% after the study period. After 72 hours of therapy, the rates of inappropriate prescribing were 48% (before study period), 32% (during study period), and 40% (after study period). During the study period, pharmacists intervened in only half of the 51 cefuroxime orders initially deemed to be inappropriate, and only 26% of these interventions resulted in an order change. Although pharmacists met with some success in increasing the appropriateness of cefuroxime prescribing, both pharmacists and physicians resumed their previous monitoring and prescribing habits after the study period had ended.

Cefuroxime↗
PubMed1989

A quality assurance audit of a drug information service.

The objectives of this study were to assess the quality of written responses provided by the Drug Information (DI) Service at The Hospital for Sick Children (HSC). A preliminary survey was circulated to 89 Canadian hospitals in December 1986 to guide us in developing this quality assurance audit. Of the 27 hospitals responding to this survey, 19 had formal DI centres. It was decided to perform our audit by means of a user satisfaction survey and a committee review of written DI responses. Fifty-six DI user surveys were distributed; 25 completed surveys were returned. Completeness of response was rated the highest (9.5 out of 10) by the respondents while the impact of the information provided on patient therapy was rated the lowest (8.3 out of 10). Sixty-three DI responses were to be reviewed by a committee which consisted of the Director, Division of Clinical Pharmacology, the Chief Medical Resident, and two pharmacists. Criteria to be examined included literature correlation/condensation, data documentation, literature evaluation, conclusions, references, organization, terminology and sentence structure. These criteria were all rated at greater than 90 percent compliance by the chief medical residents and pharmacists. Both the user survey and committee review led to the conclusion that our DI Service exhibits a high level of quality in its written responses to DI requests.

Canada↗
PubMed1987

Comparative evaluation of benzydamine oral rinse in children with antineoplastic-induced stomatitis.

This nonblinded, crossover study was undertaken to compare the extent and duration of analgesia after administration of benzydamine 0.15% oral rinse and Hospital for Sick Children (HSC) mouthwash for pain (nystatin 7000 U/ml, lidocaine viscous 0.58 ml/ml in NaCl 0.9%) in pediatric patients with antineoplastic-induced stomatitis. Each mouthwash was administered as a paint or a gargle q2h while the child was awake on two consecutive days. Patients older than three years were asked to describe their pain by means of a pictorial or a visual analog scale. Pain was assessed by the investigator, parent, or nurse caring for the patient as well as the patient whenever possible before each dose and 10, 30, and 60 minutes after the first three doses each day for four days. Stomatitis severity was graded daily. Four patients completed the study protocol; an additional three patients dropped out of the study due to severe stinging when benzydamine oral rinse was administered. The case histories of the patients who completed the study are presented. Both preparations reduced pain for at least one hour in most instances but not for two hours. Three of four patients elected to continue treatment with HSC mouthwash for pain. Study recruitment was halted due to the ethical concern of continuing with the knowledge that benzydamine oral rinse causes oral pain and stinging, especially in patients with severe stomatitis.

Adolescent↗
PubMed1987

Palatability and relative bioavailability of an extemporaneous carbamazepine oral suspension.

The palatability of five flavored and unflavored extemporaneous carbamazepine 20-mg/mL oral suspensions was tested, and the bioavailability of the unflavored suspension relative to that of the tablet used in its manufacture was determined in a randomized, crossover study of 12 healthy volunteers. Carbamazepine 400 mg was administered with a glass of water as either 20 mL of unflavored oral suspension (20 mg/mL) or two 200-mg tablets. Subjects were randomly assigned to receive first either the tablets or the suspension in crossover fashion on two days separated by at least two weeks. Blood samples were taken just before and at various times up to 72 hours after the carbamazepine dose. Serum samples were assayed for carbamazepine content by high-performance liquid chromatography. Of five flavored and unflavored carbamazepine suspensions tested in eight volunteers, the cherry-mint formulation was the least palatable. There was no trend in preference among the remaining suspensions (banana, tutti-frutti, grape, and unflavored). Mean values of maximum serum concentration and absorption rate constant were significantly greater for the unflavored suspension (5.7 mg/L [24 mumol/L] and 0.832 hr-1, respectively) than for the tablet (4.9 mg/L [20.8 mumol/L] and 0.266 hr-1, respectively). The mean time to maximum concentration was significantly shorter after suspension administration (3.87 hours) than after tablet administration (11.8 hours). There was no significant difference in the extent of absorption of the tablet and suspension formulation as reflected by the corrected values of the area under the serum concentration-versus-time curves. The mean (+/- S.D.) bioavailability of the suspension relative to the tablet was 94.46% +/- 20.42 (range 76.35-132.72%).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗