Nicolas Garbez1,2,3, Litaty C Mbatchi4,5, Guillaume Louart6,7, Steven C Wallis8, Laurent Muller6,7, Jeffrey Lipman7,8,9, Jason A Roberts7,8,9,10,11, Jean-Yves Lefrant6,7, Claire Roger6,7. 1. Service Des Réanimations, Pôle Anesthésie Réanimation Douleur Urgence, CHU Nîmes, Nîmes, France. nicolas.garbez@umontpellier.fr. 2. Laboratoire de Pharmacocinétique, Faculté de Pharmacie, Université de Montpellier, Montpellier, France. nicolas.garbez@umontpellier.fr. 3. UR-UM 103: IMAGINE (Initial Management And Prévention of orGan Failures IN Critically Ill patiEnts), Faculté de Médecine, Université de Montpellier, Montpellier, France. nicolas.garbez@umontpellier.fr. 4. Laboratoire de Pharmacocinétique, Faculté de Pharmacie, Université de Montpellier, Montpellier, France. 5. Laboratoire de Biochimie, Centre Hospitalier Universitaire (CHU) of Nîmes, Hôpital Carémeau, Nîmes, France. 6. Service Des Réanimations, Pôle Anesthésie Réanimation Douleur Urgence, CHU Nîmes, Nîmes, France. 7. UR-UM 103: IMAGINE (Initial Management And Prévention of orGan Failures IN Critically Ill patiEnts), Faculté de Médecine, Université de Montpellier, Montpellier, France. 8. UQ Centre for Clinical Research, The University of Queensland, Brisbane, QLD, Australia. 9. Jamieson Trauma Institute and Intensive Care Services, Royal Brisbane and Womens' Hospital, Brisbane, QLD, Australia. 10. Centre for Translational Anti-Infective Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, QLD, Australia. 11. Pharmacy Department, Royal Brisbane and Womens' Hospital, Brisbane, QLD, Australia.
Abstract
OBJECTIVES: To describe micafungin pharmacokinetic (PK) alterations of sepsis induced in piglets and to determine whether the porcine septic model is able to predict the PK of micafungin in septic patients at the plasma and peritoneal sites. METHODS: From healthy (n = 8) and septic piglet group (n = 16), total micafungin concentrations were subject to a population PK analysis using Monolix®. Data from 16 septic humans patients from others studies was used to compare micafungin PK between septic piglets and septic patients. RESULTS: Sepsis induced in piglets slightly alters the total clearance and the volume of distribution, while inter-compartment clearance is increased (from 3.88 to 5.74 L/h) as well as the penetration into peritoneal cavity (from 61 to 90%). In septic human patients, PK parameters are similar except for the Vd, which is corrected by an allometric factor based on the body weight of each species. Micafungin penetration into peritoneal cavity of humans is lower than in septic piglets (40 versus 90%). CONCLUSIONS: The sepsis induced in the porcine model alters the PK of micafungin comparable to that in humans. In addition, micafungin PK is similar between these two species at the plasma level taking into account the allometric relationship of the body weight of these species on the central volume of distribution. The porcine septic plasma model would be able to predict the micafungin PK in the septic patients. However, further studies on peritoneal penetration are necessary to characterize this inter-species difference.
OBJECTIVES: To describe micafungin pharmacokinetic (PK) alterations of sepsis induced in piglets and to determine whether the porcine septic model is able to predict the PK of micafungin in septic patients at the plasma and peritoneal sites. METHODS: From healthy (n = 8) and septic piglet group (n = 16), total micafungin concentrations were subject to a population PK analysis using Monolix®. Data from 16 septic humans patients from others studies was used to compare micafungin PK between septic piglets and septic patients. RESULTS: Sepsis induced in piglets slightly alters the total clearance and the volume of distribution, while inter-compartment clearance is increased (from 3.88 to 5.74 L/h) as well as the penetration into peritoneal cavity (from 61 to 90%). In septic human patients, PK parameters are similar except for the Vd, which is corrected by an allometric factor based on the body weight of each species. Micafungin penetration into peritoneal cavity of humans is lower than in septic piglets (40 versus 90%). CONCLUSIONS: The sepsis induced in the porcine model alters the PK of micafungin comparable to that in humans. In addition, micafungin PK is similar between these two species at the plasma level taking into account the allometric relationship of the body weight of these species on the central volume of distribution. The porcine septic plasma model would be able to predict the micafungin PK in the septic patients. However, further studies on peritoneal penetration are necessary to characterize this inter-species difference.
Authors: Michael Balls; Alan M Goldberg; Julia H Fentem; Caren L Broadhead; Rex L Burch; Michael F W Festing; John M Frazier; Coenraad F M Hendriksen; Margaret Jennings; Margot D O van der Kamp; David B Morton; Andrew N Rowan; Claire Russell; William M S Russell; Horst Spielmann; Martin L Stephens; William S Stokes; Donald W Straughan; James D Yager; Joanne Zurlo; Bert F M van Zutphen Journal: Altern Lab Anim Date: 1995 Nov-Dec Impact factor: 1.303