ABSTRACT
AIM: To explore the optimal dosage of dexmedetomidine for prevention of agitation induced by sevoflurane anesthesia in children. METHODS: One hundred and sixty ASA -Ⅱ pediatric patients, who underwent indirect inguinal hernia or hydrocele were randomly divided into 4 groups: C group (saline group), D0.2 group (dexmedetomidine 0.2 μg/kg), Group D0.4 (dexmedetomidine 0.4 μg/kg); D0.6 group (dexmedetomidine 0.6 μg/kg), 40 cases in each group. The dexmedetomidine was treated with intravenous infusion of the same volume of saline at 10 min before the induction of anesthesia. Observation with induction period and intraoperative hemodynamic situation, postoperative FLACC behavior score, Ramsay sedation scores, extubation time, adverse reactions, such as respiration depression (SpO20.05). The case of postoperative agitation in the group D0.4 (12 cases), D0.6 (8 cases) lower than the group C (23 cases) and D0.2 (16 cases) (P0.05).CONCLUSION:The usage of 0.4 μg/kg dexmedetomidine for the pediatric inguinal hernia or hydrocele surgery under the anesthesia of sevoflurane has the characteristics of stable hemodynamics during the operation, reducing the incidence of restlessness after sevoflurane anesthesia, not affecting the recovery of children, and not increasing adverse reactions.
ABSTRACT
This tutorial explains the basic principles of mechanistic ligand-receptor interaction model, which is an operational model of agonism. A growing number of agonist drugs, especially immune oncology drugs, is currently being developed. In this tutorial, time-dependent ordinary differential equation for simple E(max) operational model of agonism was derived step by step. The differential equation could be applied in a pharmacodynamic modeling software, such as NONMEM, for use in non-steady state experiments, in which experimental data are generated while the interaction between ligand and receptor changes over time. Making the most of the non-steady state experimental data would simplify the experimental processes, and furthermore allow us to identify more detailed kinetics of a potential drug. The operational model of agonism could be useful to predict the optimal dose for agonistic drugs from in vitro and in vivo animal pharmacology experiments at the very early phase of drug development.
Subject(s)
Animals , Felodipine , In Vitro Techniques , Kinetics , PharmacologyABSTRACT
OBJECTIVE: This study was aimed to determine effectiveness and tolerability of Osmotic-controlled Release Oral delivery (OROS) methylphenidate (MPH) and its optimal dose administered openly over a period of up to 12 weeks in drug naive Korean children with ADHD. METHODS: Subjects (n=143), ages 6 to 18-years, with a clinical diagnosis of any subtype of ADHD were recruited from 7 medical centers in Korea. An individualized dose of OROS-MPH was determined for each subject depending on the response criteria. The subjects were assessed with several symptom rating scales in week 1, 3, 6, 9 and 12. RESULTS: 77 of 116 subjects (66.4%) achieved the criteria for response and the average of optimal daily dose for response was to 30.05+/-12.52 mg per day (0.90+/-0.31 mg/kg/d) at the end of the study. Optimal dose was not significantly different between ADHD subtypes, whereas, significant higher dose was needed in older aged groups than younger groups. The average of optimal daily dose for response for the subjects aged above 12 years old was 46.38+/-15.52 per day (0.81+/-0.28 mg/kg/d) compared to younger groups (p<0.01). No serious adverse effects were reported and the dose did not have a significant effect on adverse effects. CONCLUSION: Optimal mean dose of OROS-MPH was significantly different by age groups. Higher dose was needed in older aged groups than younger groups. Effectiveness and tolerability of OROS-MPH in symptoms of ADHD is sustained for up to 12 weeks.
Subject(s)
Aged , Child , Humans , Korea , Methylphenidate , Weights and MeasuresABSTRACT
Although the establishment of appropriate dosage ranges and dose-up strategies for antipsychotic drugs has important ramifications for both short-term treatment and long-term therapeutic outcomes, difficulties in dosing persist. As a matter of fact, drug dosages utilized during controlled clinical trials are not always optimal for patients encountered in day-to-day practice. The original trials of risperidone, a novel antipsychotics, suggested that an initial target dose and dose-up schedule of 6 mg/day within 1week was appropriate, but these trials were necessarily conducted among patients who were chronically impaired, hospitalized, and often partly drug resistant. Relevant data relating to the dosage and dose-up schedule of risperidone identified through a lot of papers published in Korean and other country. On the basis of multicenter studies, naturalistic studies, phase 4 trials and many years of clinical experiences, the curre ntly recommended target dose and their schedule for risperidone treatment is 4-5 mg/day with less-rapid titration than previously recommended. Moreover, a lower dose than this and slower titration may be appropriate for elderly patients and first-episode patients.
Subject(s)
Aged , Humans , Antipsychotic Agents , Appointments and Schedules , Risperidone , SchizophreniaABSTRACT
OBJECTIVES: The present study aimed to determine the optimal clozapine dosage in Korean adult schizophrenic patients, and to measure the blood levels of clozapine and its major metabolites. METHODS: Thirty schizophrenic patients, who have undertaken clozapine over 1 year, were recruited in this study. We investigated the clozapine dose at different times(2, 4, 8, 12, 24, 52 weeks) during the course of treatment with clozapine and we measured the blood level of clozapine and its major metabolites, N-desmethylclozapine and clozapine-N-oxide by using high performance liquid chroma-tography(HPLC). RESULTS: The average dosages of clozapine at 2, 4, 8, 12, 24, 52 weeks were 22.5(+/-92.2), 330.0 (+/-139.2), 344.8(+/-80.6), 327.5(+/-93.4), 288.3(+/-118.5), 239.3(+/-112.3)mg/day respectively. The average clozapine dose of male schizophrenics was significantly higher than that of female schizo-phrenics after 8 weeks during the course of treatment. But there were no significant differences in blood level of clozapine and its major metabolites between genders in same dosage of clozapine. The average dose of clozapine in smokers was slightly higher than non-smokers, but there was no statistical significance. The blood levels of clozapine and its major metabolites was significantly correlated with the total dose of clozapine. CONCLUSION: The average clozapine dose of Korean adult schizophrenics was lower than that of reported Caucasian data, and to reach the known therapeutic clozapine blood level above 350-400 ng/ml, we need 300-400mg/day of clozapine.