ABSTRACT
BACKGROUND: The aims of this study were to investigate the effectiveness, safety, pharmacokinetics, and pharmacodynamics of microemulsion propofol, Aquafol (Daewon Pharmaceutical Co., Ltd, Seoul, Republic of Korea). METHODS: In total, 288 patients were randomized to receive 1% Aquafol or 1% Diprivan (AstraZeneca, London, UK) (n=144, respectively). A 30 mg test dose of propofol was administered i.v. over 2 s for assessing injection pain. Subsequently, a bolus of propofol 2 mg kg(-1) (-30 mg) was administered. Anaesthesia was maintained with a variable rate infusion of propofol and a target-controlled infusion of remifentanil. Mean infusion rates of both formulations and times to loss of consciousness (LOC) and recovery of consciousness (ROC) were recorded. Adverse events and pharmacokinetic and pharmacodynamic characteristics were evaluated. RESULTS: Mean infusion rate of Aquafol was not statistically different from that of Diprivan (median: 6.2 vs 6.3 mg kg(-1) h(-1)). Times to LOC and ROC were slightly prolonged in Aquafol (median: 21 vs 18 s, 12.3 vs 10.8 min). Aquafol showed similar incidence of adverse events to Diprivan. Aquafol (vs Diprivan caused more severe (median VAS: 72.0 vs 11.5 mm) and frequent (81.9 vs 29.2%) injection pain. The dose-normalized AUC(last) of Aquafol and Diprivan was 0.71 (0.19) and 0.74 (0.20) min litre(-1). The V(1) of both formulations were proportional to lean body mass. Sex was a significant covariate for k(12) and Ce(50) of Aquafol, and for k(e0) of Diprivan. CONCLUSIONS: Aquafol was as effective and safe as Diprivan, but caused more severe and frequent injection pain. Aquafol demonstrated similar pharmacokinetics to Diprivan.
Subject(s)
Anesthetics, Intravenous/chemistry , Propofol/chemistry , Adult , Analgesics, Opioid/administration & dosage , Anesthesia, Intravenous/methods , Anesthetics, Intravenous/adverse effects , Anesthetics, Intravenous/blood , Chemistry, Pharmaceutical , Double-Blind Method , Drug Administration Schedule , Elective Surgical Procedures , Emulsions , Female , Humans , Male , Middle Aged , Pain/chemically induced , Pain Measurement/methods , Pain, Postoperative/prevention & control , Postoperative Nausea and Vomiting/chemically induced , Propofol/adverse effects , Propofol/bloodABSTRACT
BACKGROUND AND PURPOSE: Microemulsion propofol was developed to eliminate lipid solvent-related adverse events of long-chain triglyceride emulsion (LCT) propofol. We compared dose proportionality, pharmacokinetic and pharmacodynamic characteristics of both formulations. EXPERIMENTAL APPROACH: The study was a randomized, two-period and crossover design with 7-day wash-out period. Microemulsion and LCT propofol were administered by zero-order infusion (0.75, 1.00 and 1.25 mg kg(-1) min(-1)) for 20 min in 30 beagle dogs (male/female = 5/5 for each rate). Arterial samples were collected at preset intervals. The electroencephalographic approximate entropy (ApEn) was used as a measure of propofol effect. Dose proportionality, pharmacokinetic and pharmacodynamic bioequivalence were evaluated by non-compartmental analyses. Population analysis was performed using nonlinear mixed effects modelling. KEY RESULTS: Both formulations showed dose proportionality at the applied dose range. The ratios of geometric means of AUC(last) and AUC(inf) between both formulations were acceptable for bioequivalence, whereas that of C(max) was not. The pharmacodynamic bioequivalence was indicated by the arithmetic means of AAC (areas above the ApEn time curves) and E(0) (baseline ApEn)-E(max) (maximally decreased ApEn) between both formulations. The pharmacokinetics of both formulations were best described by three compartment models. Body weight was a significant covariate for V(1) of both formulations and sex for k(21) of microemulsion propofol. The blood-brain equilibration rate constants (k(e0), min(-1)) were 0.476 and 0.696 for microemulsion and LCT propofol respectively. CONCLUSIONS AND IMPLICATIONS: Microemulsion propofol was pharmacodynamically bioequivalent to LCT propofol although pharmacokinetic bioequivalence was incomplete, and demonstrated linear pharmacokinetics at the applied dose ranges.
Subject(s)
Anesthetics, Intravenous/administration & dosage , Propofol/administration & dosage , Triglycerides/chemistry , Anesthetics, Intravenous/pharmacokinetics , Anesthetics, Intravenous/pharmacology , Animals , Area Under Curve , Body Weight , Cross-Over Studies , Dogs , Dose-Response Relationship, Drug , Electroencephalography , Emulsions , Entropy , Female , Male , Models, Biological , Nonlinear Dynamics , Propofol/pharmacokinetics , Propofol/pharmacology , Random Allocation , Therapeutic Equivalency , Tissue DistributionSubject(s)
Antibodies, Monoclonal/therapeutic use , Choroidal Neovascularization/drug therapy , Choroiditis/complications , Immunologic Factors/therapeutic use , Adult , Antibodies, Monoclonal, Humanized , Choroidal Neovascularization/complications , Female , Humans , Ranibizumab , Treatment Outcome , Visual AcuitySubject(s)
Antibodies, Monoclonal/therapeutic use , Choroid Neoplasms/complications , Choroidal Neovascularization/drug therapy , Immunologic Factors/therapeutic use , Osteoma/complications , Adult , Antibodies, Monoclonal, Humanized , Choroidal Neovascularization/etiology , Female , Humans , Intravitreal Injections , Ranibizumab , Treatment Outcome , Visual AcuityABSTRACT
Coronary artery bypass graft (CABG) patients often have cerebrovascular disease and pre-operative brain magnetic resonance angiography (MRA) frequently reveals cerebral vasculature stenosis. This study was designed to investigate whether pre-operative MRA findings correlated with regional cerebral oxygen saturation (ScO(2)) in 120 patients undergoing on-pump or off-pump CABG. Following MRA examination, patients were divided into six groups of 20 patients each based on MRA findings (no stenosis, mild stenosis or severe stenosis) and procedure (on-pump or off-pump CABG). Mean ScO(2) values over 3 min were determined at seven periods during surgery. Patients with severe cerebrovascular stenosis showed significantly lower ScO(2) than other groups during off-pump CABG. During on-pump CABG, ScO(2) decreased significantly during cardiopulmonary bypass in all groups and was significantly lower in the severe stenosis group. Pre-operative MRA and intra-operative ScO(2) monitoring may help to identify patients at increased risk of brain damage during or following CABG.
Subject(s)
Brain/diagnostic imaging , Brain/metabolism , Coronary Artery Bypass , Magnetic Resonance Angiography , Oxygen/metabolism , Preoperative Period , Demography , Female , Humans , Intraoperative Period , Male , Middle Aged , RadiographyABSTRACT
PURPOSE: This study was conducted to develop gerontological curriculum model which reflects the need of Korean society. METHOD: Three round Delphi survey method was applied to find consensus of gerontological nursing competencies (knowledge, attitudes and skills) for graduates of nursing schools from the panel of gerontological nursing practice experts. Important concepts in gerontological nursing were delineated from literature review and discussions of gerontological nursing educators. Based on these results the gerontological nursing curriculum model was developed and course structure outlined by the researchers as a group. RESULT: As the result of delphi survey, 32 items of knowledge, 29 items of attitude, and 21 items of skill were identified. The curriculum model constructed around a cube with three plane- functional capacity levels, settings, and nursing practice. Specific knowledge, attitudes and skills for gerontological theory and practicum course were suggested. Competency items were assigned to theory and/or practice. CONCLUSION: A curriculum model for gerontological nursing has been developed by a group of gerontological nursing educators. The curriculum model should be further tested and developed with detailed theory and practicum course outline and textbooks.
