Pharmacokinetic-Pharmacodynamic Modeling in Pediatric Drug Development, and the Importance of Standardized Scaling of Clearance.

Pharmacokinetic/pharmacodynamic (PKPD) modeling is important in the design and conduct of clinical pharmacology research in children. During drug development, PKPD modeling and simulation should underpin rational trial design and facilitate extrapolation to investigate efficacy and safety. The application of PKPD modeling to optimize dosing recommendations and therapeutic drug monitoring is also increasing, and PKPD model-based dose individualization will become a core feature of personalized medicine. Following extensive progress on pediatric PK modeling, a greater emphasis now needs to be placed on PD modeling to understand age-related changes in drug effects. This paper discusses the principles of PKPD modeling in the context of pediatric drug development, summarizing how important PK parameters, such as clearance (CL), are scaled with size and age, and highlights a standardized method for CL scaling in children. One standard scaling method would facilitate comparison of PK parameters across multiple studies, thus increasing the utility of existing PK models and facilitating optimal design of new studies

Evaluation of postoperative pain scores following ultrasound guided transversus abdominis plane block versus local infiltration following day surgery laparoscopic cholecystectomy-retrospective study

Background and Aims: Postoperative pain for day surgery laparoscopic cholecystectomy has traditionally been managed with the surgeon infiltrating the wound with local anesthetic (LA). However, transversus abdominis plane (TAP) block has recently been used, although its superiority over LA remains uncertain. The primary aim was to compare LA and TAP block pain scores and analgesia used. The secondary aim was to assess satisfaction score and cost. Material and Methods: This retrospective study was commenced after ethics committee approval and ANZ clinical trial registry (ACTRN: 12612000737831). The data were collected from the theatre database and medical records of patients presenting for day case laparoscopic cholecystectomy. The sample included patients who received either bilateral port site LA infiltration with 20 ml of 0.25% Bupivacaine or bilateral TAP block with 20 ml of 0.5% ropivacaine and fentanyl postoperative pain protocol. The patients with incomplete medical records were excluded as were those admitted to an inpatient ward. Demographics and clinical characteristics were obtained from the hospital record along with pain score and postsurgery analgesia use. Postoperative pain satisfaction scores were collected by telephonic interview 30-180 days postsurgery. Results: Of 51 patients analyzed, 19 were in TAP group 29 in LA group. There were no significant differences between the LA and TAP groups with respect to postoperative pain scores (P = 0.31) or patient satisfaction scores (1 and 2+) (P = 0.36). However, fentanyl consumption in the recovery room was significantly lower in TAP group (P = 0.0079.). The consumables cost were >3 times higher in the TAP when compared to LA group. Conclusion: The performance of the TAP block with respect to pain management was comparable to LA. However, LA remains more cost effective

Ultrasound-guided continuous transverse abdominis plane block for abdominal surgery

Introduction: Transversus abdominis plane (TAP) block is a new regional analgesic technique for postoperative pain in abdominal surgery. Its efficacy is not clear, and thus it needs to be explored for its regular utilisation on prolonged period. The objective was to study the continuous local anaesthetic infusion effect on postoperative analgesia. Continuous use of TAP block as an analgesic technique has not been evaluated prospectively in clinical trials. This study evaluates the efficacy of ultrasound-guided TAP block in comparison with PCA fentanyl in major abdominal surgery. Materials and Methods: There were 20 patients in the study, allocated to TAP and control groups. The parameters measured were pain scores on a numerical rating scale (NRS) of 0-10 at various time intervals and the amount of fentanyl used as rescue analgesia. Patient satisfaction scores were recorded in the TAP block group and along with any complications related to the block. Results: The postoperative median pain scores on coughing on day one were 6.0 for control group and 2.0 for the TAP group (P0 = 0.02); on day two, the equivalent scores were 7.0 and 2.0 (P = 0.01). The fentanyl requirement at one hour was 203 μ for the control group and 78 μg for the TAP group (P = 0.03); at day one, the control and TAP requirements were 1237 μg and 664 μg respectively (P = 0.01). Three TAP patients rated their satisfaction as 'excellent', four as 'satisfied, and two as 'poor'. Conclusion: TAP block is a promising technique for postoperative analgesia in major abdominal surgeries. Our study demonstrated lower pain scores in the TAP group with reduced fentanyl requirement. Further, a large scale study is needed to establish the efficacy of TAP block in this setting.Rao V Kadam, JB Fiel

Luminescence and EPR studies of YBO(3):U

Yttrium borate doped with uranium was prepared by mixing and heating yttrium oxide obtained through oxalate precipitation route, boric acid and requisite amount of nuclear-grade uranium oxide at high temperature. Photoluminescence (PL), thermally stimulated luminescence (TSL) and electron paramagnetic resonance (EPR) studies were carried out on gamma-irradiated doped/undoped yttrium borate samples in the temperature range 300-600K. TSL studies showed the presence of two glow peaks at 414 and 471 K. PL studies along with lifetime decay investigation suggested uranium goes in the matrix as UO(2)(2+). EPR studies showed the presence of O(2)(-)radical ion along with electron trapped in defect centres, which might have been produced for charge compensation. Apart from this, CO(2)(-) radical was also observed in the system having its origin from residual oxalate ion. Temperature dependence EPR studies of the observed radical confirmed the involvement of the CO(2)(-) and dioxide radical ion in the observed glow peaks. By correlating the TSL, PL and ESR data, probable mechanism is proposed for the observed TSL glow in the system. (C) 200