caa a22 4500 47712836X CHVBK 20180405111656.0 cr unu---uuuuu 170330e19971101xx s 000 0 eng 10.1023/A:1012130402199 doi (NATIONALLICENCE)springer-10.1023/A:1012130402199 Time-dependent Pharmacokinetics of High Dose Thiopental Infusion in Intensive Care Patients [Elektronische Daten] [Hélène Russo, Marie Dubboin, Françoise Bressolle, Saïk Urien] Purpose. In patients with severe head injuries receiving long-term infusion for reducing intracranial pressure, a decline in concentrations was apparent following attainment of an initial steady state. This could be explained by an increased rate of elimination. An adequate modeling of the plasma disposition curves was used to demonstrate clearly the metabolic induction. Methods. The concentration-time data of 17 patients were fit by a one compartment pharmacokinetic model in which the decline of plasma concentration during infusion was due to an increase in the clearance rate of thiopental following a latency period. This time-dependent clearance model provided estimates of initial and final clearance rates. Results. This study demonstrated that large interindividual variations were observed during the course of the thiopental time-dependent pharmacokinetics. Depending on the patient, one or two steps of induction occurred. The mean initial and final clearance rates were 1.22 ± 0.82 mL/min/kg and 10.5 ± 23 mL/min/kg. The latency period for the first induction averaged 69 ± 56 h. For 6 subjects, the rate of thiopental metabolism continued to change with time and there was a second step of induction. Conclusions. Induction of thiopental metabolism occur within therapeutic ranges, but it was not established that attainment of individual limits in dosing rate, total dose, or treatment duration occur in the process. Thus, monitoring is needed for achievement of a target plasma concentration. Plenum Publishing Corporation, 1997 thiopental nationallicence long term infusion nationallicence time-dependent clearance model nationallicence critically ill patients nationallicence Russo Hélène Pharmacie Saint Eloi, Centre Hospitalier Universitaire, 34295, Montpellier Cedex 5, France aut Dubboin Marie Département d'Anesthésie-Réanimation (DAR B), Hôpital Saint Eloi, Centre Hospitalier Universitaire, 34295, Montpellier, France aut Bressolle Françoise Faculté de Pharmacie, Laboratoire de Pharmacocinétique, 34060, Montpellier, France aut Urien Saïk Laboratoire de Pharmacologie, Faculté de Médecine, Université Paris XII, 94010, Créteil, France aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/11(1997-11-01), 1583-1588 0724-8741 14:11<1583 1997 14 11095 https://doi.org/10.1023/A:1012130402199 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012130402199 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Russo Hélène Pharmacie Saint Eloi, Centre Hospitalier Universitaire, 34295, Montpellier Cedex 5, France aut NATIONALLICENCE 700 1- Dubboin Marie Département d'Anesthésie-Réanimation (DAR B), Hôpital Saint Eloi, Centre Hospitalier Universitaire, 34295, Montpellier, France aut NATIONALLICENCE 700 1- Bressolle Françoise Faculté de Pharmacie, Laboratoire de Pharmacocinétique, 34060, Montpellier, France aut NATIONALLICENCE 700 1- Urien Saïk Laboratoire de Pharmacologie, Faculté de Médecine, Université Paris XII, 94010, Créteil, France aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/11(1997-11-01), 1583-1588 0724-8741 14:11<1583 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer