Non-linear elimination processes of theophylline

1983 ◽  
Vol 24 (1) ◽  
pp. 71-78 ◽  
Author(s):  
U. Gundert-Remy ◽  
R. Hildebrandt ◽  
N. Hengen ◽  
E. Weber
Keyword(s):  
Non Linear ◽  
Linear Elimination

scholarly journals A preclinical study to model taurine pharmokinetics in the undernourished rat

2018 ◽  
Vol 119 (7) ◽  
pp. 826-835 ◽  
Author(s):  
Ana Catalán-Latorre ◽  
Amparo Nácher ◽  
Virginia Merino ◽  
Octavio Díez ◽  
Matilde Merino Sanjuán
Keyword(s):  
Preclinical Study ◽  
Population Pharmacokinetic ◽  
Process Data ◽  
Internal Organs ◽  
Linear Absorption ◽  
First Order Kinetics ◽  
Protein Energy ◽  
Non Linear ◽  
Linear Elimination ◽  
Passive Absorption

AbstractMalnutrition is a common feature of chronic and acute diseases, often associated with a poor prognosis, including worsening of clinical outcome, owing, among other factors, to dysfunction of the most internal organs and systems affecting the absorption, metabolism and elimination of drugs and nutrients. Taurine is involved in numerous biological processes and is required in increased amounts in response to pathological conditions. The aim of this study was to describe the behaviour of taurine in well-nourished (WN) rats and to analyse the influence of protein–energy undernutrition on the pharmacokinetic (PK) parameters of taurine, using a PK model. Wistar rats were randomly distributed into two groups, WN and undernourished (UN), and taurine was administered intravenously or orally at different doses: 1, 10 and 100 mg. Population pharmacokinetic modelling of plasma levels was performed using the NONMEM 7.2 program. Several distribution and absorption models were explored in combination with dose and/or time covariate effects. Covariates such as nutritional status, serum albumin, body weight and score of undernutrition were used. A two-compartment population pharmacokinetic model with zero-order endogenous formation, passive absorption, first-order kinetics distribution and non-linear elimination with parallel Michaelis–Menten excretion and reabsorption processes best described taurine pharmacokinetics. Undernutrition acted as a covariate reducing theVmaxof the active elimination process. Data analysis showed linear absorption and distribution, and non-linear elimination processes for taurine. Elimination of taurine was reduced in UN animals, suggesting that the reabsorption process via the secretion transporter was modified in that group.

scholarly journals Characterizing the non-linear pharmacokinetics of miltefosine in paediatric visceral leishmaniasis patients from Eastern Africa

2020 ◽  
Vol 75 (11) ◽  
pp. 3260-3268
Author(s):  
Semra Palić ◽  
Anke E Kip ◽  
Jos H Beijnen ◽  
Jane Mbui ◽  
Ahmed Musa ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Cumulative Dose ◽  
Drug Exposure ◽  
Compartment Model ◽  
Eastern Africa ◽  
Model Following ◽  
Two Compartment Model ◽  
Non Linear ◽  
Linear Elimination ◽  
Dosing Regimens

Abstract Background Conventional miltefosine dosing (2.5 mg/kg/day) for treatment of visceral leishmaniasis (VL) is less effective in children than in adults. A higher allometric dose (median 3.2 mg/kg/day) was therefore investigated in paediatric VL patients in Eastern Africa. Results of this trial showed an unforeseen, lower than dose-proportional increase in exposure. Therefore, we performed a pooled model-based analysis of the paediatric data available from both dosing regimens to characterize observed non-linearities in miltefosine pharmacokinetics (PK). Methods Fifty-one children with VL were included in this analysis, treated with either a conventional (n = 21) or allometric (n = 30) miltefosine dosing regimen. PK data were analysed using non-linear mixed-effects modelling. Results A two-compartment model following first-order absorption and linear elimination, with two separate effects on relative oral bioavailability, was found to fit these data best. A 69% lower bioavailability at treatment start was estimated, presumably due to initial malnourishment and malabsorption. Stagnation in miltefosine accumulation in plasma, hampering increased drug exposure, was related to the increase in cumulative dose (mg/kg/day). However, the allometric regimen increased exposure 1.7-fold in the first treatment week and reduced the time to reach the PK target by 17.4%. Conclusions Miltefosine PK in children suffering from VL are characterized by dose-dependent non-linearities that obstruct the initially expected exposure levels. Bioavailability appeared to be affected by the cumulative dose, possibly as a consequence of impaired absorption. Despite this, allometric dosing led to a faster target achievement and increased exposure compared with conventional dosing.

scholarly journals Comparison of the Pharmacokinetic Modeling of Aprindine Using a Linear and Non-linear Elimination Model.

1997 ◽  
Vol 23 (2) ◽  
pp. 115-120 ◽  
Author(s):  
KOJI TANIKAWA ◽  
YOSHIAKI MATSUMOTO ◽  
HARUKI MUSHA ◽  
MITSUO MATSUMOTO
Keyword(s):  
Pharmacokinetic Modeling ◽  
Non Linear ◽  
Linear Elimination

Non-linear elimination and protein binding of probenecid

1987 ◽  
Vol 32 (4) ◽  
pp. 395-401 ◽  
Author(s):  
B -M. Emanuelsson ◽  
B. Beermann ◽  
L. K. Paalzow
Keyword(s):  
Protein Binding ◽  
Non Linear ◽  
Linear Elimination

scholarly journals Kinetic‐pharmacodynamic model for drugs with non‐linear elimination: Parameterisation matters

2020 ◽  
Vol 86 (2) ◽  
pp. 196-198
Author(s):  
Qing Xi Ooi ◽  
Chihiro Hasegawa ◽  
Stephen B. Duffull ◽  
Daniel F.B. Wright
Keyword(s):  
Pharmacodynamic Model ◽  
Non Linear ◽  
Linear Elimination

B. The Non-Linear Calculations for Pulsating Stars

1967 ◽  
Vol 28 ◽  
pp. 105-176
Author(s):  
Robert F. Christy
Keyword(s):  
Major Part ◽  
Afternoon Session ◽  
Discussion Session ◽  
Pulsating Stars ◽  
Fourth Symposium ◽  
Non Linear ◽  
Considerable Discussion ◽  
Informal Approach ◽  
Preceding Session

(Ed. note: The custom in these Symposia has been to have a summary-introductory presentation which lasts about 1 to 1.5 hours, during which discussion from the floor is minor and usually directed at technical clarification. The remainder of the session is then devoted to discussion of the whole subject, oriented around the summary-introduction. The preceding session, I-A, at Nice, followed this pattern. Christy suggested that we might experiment in his presentation with a much more informal approach, allowing considerable discussion of the points raised in the summary-introduction during its presentation, with perhaps the entire morning spent in this way, reserving the afternoon session for discussion only. At Varenna, in the Fourth Symposium, several of the summaryintroductory papers presented from the astronomical viewpoint had been so full of concepts unfamiliar to a number of the aerodynamicists-physicists present, that a major part of the following discussion session had been devoted to simply clarifying concepts and then repeating a considerable amount of what had been summarized. So, always looking for alternatives which help to increase the understanding between the different disciplines by introducing clarification of concept as expeditiously as possible, we tried Christy's suggestion. Thus you will find the pattern of the following different from that in session I-A. I am much indebted to Christy for extensive collaboration in editing the resulting combined presentation and discussion. As always, however, I have taken upon myself the responsibility for the final editing, and so all shortcomings are on my head.)

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