caa a22 4500 477058108 CHVBK 20180405111352.0 cr unu---uuuuu 170330e19960101xx s 000 0 eng 10.1007/BF00226335 doi (NATIONALLICENCE)springer-10.1007/BF00226335 A pharmacokinetic-pharmacodynamic model for a muscle relaxant: atracurium [Elektronische Daten] [V. Nigrovic, J. Gaspari, M. Banoub] Our goal was to develop a pharmacokinetic-pharmacodynamic model that describes the fate of atracurium and its metabolite laudanosine as well as the time course of the neuromuscular block. The model was based on the consideration of mass balance of atracurium and was constructed by postulating an effect compartment linked to the central compartment in the previously described open mammillary model for atracurium. The entry and exit rate constants, kCE and kEC, were adjusted to satisfy the requirement that the peak amount in the effect compartment coincides with the peak submaximal block. We used previously published clinical data to arrive at the times to 50% neuromuscular block either during the onset of the block following an ED50 dose or during the recovery following larger doses of atracurium. Laplace transforms were used to define the model, and the solution was obtained by iterative numeric adjustments of the rate constants. The model provides an excellent fit of the observed plasma concentrations of atracurium and laudanosine and simulates well the development and waning of the neuromuscular block. The model projects that the peak amount of atracurium in the effect compartment amounts to 14% of the injected dose and is reached at 7.6 min after the injection. Springer-Verlag, 1996 Pharmacokinetic-pharmacodynamic model nationallicence Atracurium nationallicence muscle relaxants nationallicence effect compartment nationallicence Nigrovic V. Department of Anesthesiology, Medical College of Ohio, P.O. Box 10008, 43699-0008, Toledo, OH, USA aut Gaspari J. Department of Anesthesiology, Medical College of Ohio, P.O. Box 10008, 43699-0008, Toledo, OH, USA aut Banoub M. Department of Anesthesiology, Medical College of Ohio, P.O. Box 10008, 43699-0008, Toledo, OH, USA aut European Journal of Clinical Pharmacology Springer-Verlag 49/4(1996-01-01), 325-332 0031-6970 49:4<325 1996 49 228 https://doi.org/10.1007/BF00226335 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00226335 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Nigrovic V. Department of Anesthesiology, Medical College of Ohio, P.O. Box 10008, 43699-0008, Toledo, OH, USA aut NATIONALLICENCE 700 1- Gaspari J. Department of Anesthesiology, Medical College of Ohio, P.O. Box 10008, 43699-0008, Toledo, OH, USA aut NATIONALLICENCE 700 1- Banoub M. Department of Anesthesiology, Medical College of Ohio, P.O. Box 10008, 43699-0008, Toledo, OH, USA aut NATIONALLICENCE 773 0- European Journal of Clinical Pharmacology Springer-Verlag 49/4(1996-01-01), 325-332 0031-6970 49:4<325 1996 49 228 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer