Browsing by Author "Ibacache Figueroa, Mauricio Enrique"

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    Modeling and Simulations in Latin-American Generic Markets: Perspectives from Chilean Local Industry, Regulatory Agency, and Academia
    (AMER CHEMICAL SOC, 2024) Garcia, Mauricio A.; Paulos, Claudio; Vinales, Manuel Ibarra; Michelet, Robin; Cabrera-Pérez, Miguel Ángel; Aceituno, Alexis; Bone, Michelle; Ibacache Figueroa, Mauricio Enrique; Cortínez Fernández, Luis Ignacio; Guzman, Marcelo
    In the last 20 years, modeling and simulations (M&S) have gained increased attention in pharmaceutical sciences. International industry and world-reference agencies have used M&S to make cost-efficient decisions through the model-informed drug development (MIDD) framework. Modeling tools include biopredictive dissolution models, physiologically based pharmacokinetic models (PBPK), biopharmaceutic models (PBBM), and virtual bioequivalence, among many others. Regulatorily, health agencies are becoming more and more open to accept the use of M&S to support regulatory applications, including setting dissolution specifications, quality-by-design (QbD), postapproval changes (SUPAC), etc. Nonetheless, the potential of M&S has been only barely explored in Latin America (Latam) across different actors: industry, regulatory agencies, and even academia. In this manuscript, we discuss the challenges and opportunities for implementing M&S approaches in Latam. Perspectives of regional experts were shared in a workshop. Attendance (professionals from industry, regulator, academia, and clinicians) also shared their views via survey. The rational development of bioequivalent generics was considered the main opportunity for M&S in regional market, particularly the use of PBPK and PBBM. Nonetheless, a critical mass of modeling scientists is needed before Latin American industry and regulators can actually benefit from M&S. Collaborations (e.g., Academia-Industry and Academia-Regulatory) may be a path to develop applied research projects and train the future modelers. Reaching that critical mass, scientists from industry may apply modeling across generic drug development process and life cycle, while regulatory scientists may issue guidelines in local language to support regional industry. Only at that stage could the full potential of MIDD be reached in Latin American generic markets.
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    Population pharmacokinetics of amikacin in suspected cases of neonatal sepsis
    (Wiley, 2023) Severino Cuevas, Nicolás Felipe; Urzúa Baquedano, Maria Soledad; Ibacache Figueroa, Mauricio Enrique; Paulos Arenas, Claudio; Cortinez Fernandez, Luis Ignacio; Toso Milos, Alberto Antonio; Leguizamon Marino, Liliana Marcela; Inojosa Mackenzie, Fernanda; Maccioni Romero, Andrea Ana; Meza Cañas, Sebastián Jaime; Garcia, Andres; Ramirez, Marcelo; Von Mentlen Gutierrez, Catalina Paz; Ceballos Jorquera Javiera Nicol; Paredes Galvez, Noemi Saray
    Aims:This study aimed to characterize the population pharmacokinetic parameters of intravenously administered amikacin in newborns and assess the effect of sepsis in amikacin exposure. Methods: Newborns aged >= 3 days who received at least 1 dose of amikacin during their hospitalization period were eligible for the study. Amikacin was administered intravenously during a 60-min infusion period. Three venous blood samples were taken from each patient during the first 48 h. Population pharmacokinetic parameter estimates were obtained using a population approach with the programme NONMEM. ResultsData from 329 drug assay samples were obtained from 116 newborn patients (postmenstrual age [PMA] 38.3, range 32-42.4 weeks; weight 2.8, range 1.6-3.8 kg). Measured amikacin concentrations ranged from 0.8 to 56.4 mg/L. A 2-compartment model with linear elimination produced a good fit of the data. Estimated parameters for a typical subject (2.8 kg, 38.3 weeks) were clearance (Cl = 0.16 L/h), intercompartmental clearance (Q = 0.15 L/h), volume of distribution of the central compartment (Vc = 0.98 L) and peripheral volume of distribution (Vp = 1.23 L). Total bodyweight, PMA and the presence of sepsis positively influenced Cl. Plasma creatinine concentration and circulatory instability (shock) negatively influenced Cl. ConclusionOur main results confirm previous findings showing that weight, PMA and renal function are relevant factors influencing newborn amikacin pharmacokinetics. In addition, current results showed that pathophysiological states of critically ill neonates, such as sepsis and shock, were associated with opposite effects in amikacin clearance and should be considered in dose adjustments.
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    Remifentanil requirements during propofol administration to block the somatic response to skin incision in children and adults
    (2007) Muñoz Letelier, Hernán Rodrigo; Cortínez Fernández, Luis Ignacio; Ibacache Figueroa, Mauricio Enrique; Altermatt Couratier, Fernando René
    BACKGROUND: During sevoflurane administration, children require a remifentanil infusion rate twofold higher than adults to block responses to skin incision. Similar data concerning remifentanil requirements are unavailable during total IV anesthesia.", "METHODS: We prospectively determined the infusion rate (IR) of remifentanil necessary to block the somatic response to skin incision in 50% (IR50) of adults (n = 20, aged 20-60 yr) and children (n = 20, aged 3-11 yr) during propofol anesthesia., In each patient undergoing lower abdominal surgery, a remifentanil infusion was initiated, followed by target-controlled infusion of propofol set at a plasma concentration of 6 mu g/mL. After tracheal intubation, propofol was reduced to 3 mu g/mL, until the end of the study. Remifentanil IR was determined according to Dixon's up-and-down method, with the first patient in each group receiving 0.2 mu g (.) kg(-1) (.) min(-1) followed by the consecutive patient receiving 0.02 mu g (.) kg(-1) (.) min(-1) modifications according to the response of the previous patient. The remifentanil IR was kept unchanged for at least 20 min before surgery. At the beginning of surgery, only the skin incision was performed, and the somatic response was observed. If there was any gross movement of extremity the response was considered positive.", "RESULTS: The IR50 (CI95%) was 0.08 (0.06-0.12) mu g (.) kg(-1) (.) min(-1) in adults and 0.15 (0.13-0.17) mu g (.) kg(-1) (.) min(-1) in children (P < 0.001).", "CONCLUSION: These results demonstrate that, similar to sevoflurane anesthesia, during total IV anesthesia with propofol, children require a remifentanil IR almost twofold higher than adults to block the somatic response to skin incision.