Nonlinear kinetics of threo-methylphenidate enantiomers in a patient with narcolepsy and in healthy volunteers

1993 ◽  
Vol 44 (1) ◽  
pp. 79-84 ◽  
Author(s):  
T. Aoyama ◽  
H. Kotaki ◽  
T. Sasaki ◽  
Y. Sawada ◽  
Y. Honda ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Nonlinear Kinetics ◽  
Kinetics Of ◽  
Methylphenidate Enantiomers

Disposition Kinetics of Disopyramide in Human Healthy Volunteers Described by an Open Three Compartment Model

1989 ◽  
Vol 64 (5) ◽  
pp. 412-416 ◽  
Author(s):  
Jan Bonde ◽  
Niels Melchior Jensen ◽  
Lars E. Pedersen ◽  
Helle R. Angelo ◽  
Seren N. Rasmussen ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Compartment Model ◽  
Disposition Kinetics ◽  
Three Compartment Model ◽  
Kinetics Of

scholarly journals New Insights Into the Kinetics and Variability of Egg Excretion in Controlled Human Hookworm Infections

2019 ◽  
Vol 220 (6) ◽  
pp. 1044-1048 ◽  
Author(s):  
Marie-Astrid Hoogerwerf ◽  
Luc E Coffeng ◽  
Eric A T Brienen ◽  
Jacqueline J Janse ◽  
Marijke C C Langenberg ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Vaccine Efficacy ◽  
Hookworm Infection ◽  
Plateau Phase ◽  
Necator Americanus ◽  
Infective Larvae ◽  
Egg Density ◽  
Kinetics Of ◽  
Hookworm Infections ◽  
Efficacy Studies

Abstract Four healthy volunteers were infected with 50 Necator americanus infective larvae (L3) in a controlled human hookworm infection trial and followed for 52 weeks. The kinetics of fecal egg counts in volunteers was assessed with Bayesian multilevel analysis, which revealed an increase between weeks 7 and 13, followed by an egg density plateau of about 1000 eggs/g of feces. Variation in egg counts was minimal between same-day measurements but varied considerably between days, particularly during the plateau phase. These analyses pave the way for the controlled human hookworm model to accelerate drug and vaccine efficacy studies.

Thermodynamic Structure of Nonlinear Macrokinetics in Reaction-Diffusion Systems

2004 ◽  
Vol 11 (02) ◽  
pp. 185-202 ◽  
Author(s):  
Stanisław Sieniutycz
Keyword(s):  
Chemical Reactions ◽  
Reaction Diffusion ◽  
Transport Processes ◽  
Mass Action ◽  
Nonlinear Kinetics ◽  
Reaction Diffusion Systems ◽  
Thermodynamic Structure ◽  
Far From Equilibrium ◽  
Physical Consequences ◽  
Kinetics Of

Affinity picture — new for transport phenomena — and the traditional Onsagerian picture are shown to constitute two equivalent representations for kinetics of chemical reactions and transfer processes. Two competing directions in elementary chemical or transport steps are analyzed. Nonequilibrium systems are described by equations of nonlinear kinetics of Marcelin-Kohnstamm-de Donder type that contain terms exponential with respect to the Planck potentials and temperature reciprocal. Simultaneously these equations are analytical expressions characterizing the transport of the substance or energy through the energy barrier. We regard kinetics of this sort as potential representations of a generalized law of mass action that includes the effect of transfer phenomena and external fields. We also consider physical consequences of these kinetics closely and far from equilibrium, and show how diverse processes can be described. In these developments we point out the significance of nonlinear symmetries and generalized affinity. Correspondence with the Onsager's theory is shown in the vicinity of thermodynamic equilibrium. Yet, the theory shows that far from equilibrium the rates of transport processes and chemical reactions cannot be determined uniquely in terms of their affinities because these rates depend on all state coordinates of the system.

scholarly journals Naloxone Reversal of Morphine- and Morphine-6-Glucuronide-induced Respiratory Depression in Healthy Volunteers

2010 ◽  
Vol 112 (6) ◽  
pp. 1417-1427 ◽  
Author(s):  
Erik Olofsen ◽  
Eveline van Dorp ◽  
Luc Teppema ◽  
Leon Aarts ◽  
Terry W. Smith ◽  
...  
Keyword(s):  
Treatment Group ◽  
Healthy Volunteers ◽  
Respiratory Depression ◽  
Simulation Study ◽  
Pharmacodynamic Model ◽  
Dissociation Kinetics ◽  
Opioid Agonist ◽  
Respiratory Effect ◽  
End Tidal ◽  
Kinetics Of

Background Opioid-induced respiratory depression is antagonized effectively by the competitive opioid receptor antagonist naloxone. However, to fully understand the complex opioid agonist-antagonist interaction, the effects of various naloxone doses on morphine and morphine-6-glucuronide (M6G)-induced respiratory depression were studied in healthy volunteers. Methods Twenty-four subjects received 0.15 mg/kg morphine intravenously at t = 0 followed by placebo, 200 or 400 microg naloxone at t = 30 min. Thirty-two subjects received 0.3 mg/kg M6G intravenously at t = 0 followed by placebo, 25, 100, or 400 microg naloxone at t = 55 min. There were a total of 8 subjects per treatment group. Respiration was measured on a breath-to-breath basis at constant end-tidal Pco2. A mechanism-based pharmacokinetic-pharmacodynamic model consisting of a part describing biophase equilibration and a part describing receptor association-dissociation kinetics was used to analyze the data. Results Naloxone reversal of M6G-induced respiratory depression developed more slowly than reversal of the respiratory effect of morphine. A simulation study revealed that this was related to the slower receptor association-dissociation kinetics of M6G (koff M6G = 0.0327 +/- 0.00455 min versus morphine 0.138 +/- 0.0148 min; values are typical +/-SE). Duration of naloxone reversal was longer for M6G. This was related to the three- to fourfold greater potency of naloxone as an antagonist against M6G compared with morphine. Increasing the naloxone dose had no effect on the speed of reversal, but it did extend reversal duration. Conclusions Naloxone reversal of the opioid effect is dependent on the receptor association-dissociation kinetics of the opioid that needs reversal with respect to the rate of reversal. The pharmacodynamics of naloxone determines reversal magnitude and duration.

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