Methodology for pharmacokinetic/pharmacodynamic data analysis

Gabrielsson, Johan; Weiner, Daniel

doi:10.1016/s1461-5347(99)00162-5

Cited by 173 publications

(199 citation statements)

References 3 publications

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“…A major strength of dose response analysis is that it allows for interpretation of responses in terms of conventional pharmacodynamic parameters such as ED50 and maximum response. Also, it enables a quantitative, statistically supported comparison of well-defined parameters, for example between patient groups or between different drugs (Gabrielsson and Weiner, 1999).…”

Section: Drug Delivery Protocols and Data Analysismentioning

confidence: 99%

Transdermal iontophoresis as an in-vivo technique for studying microvascular physiology

Tesselaar

Sjöberg

2011

Microvascular Research

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Section: Drug Delivery Protocols and Data Analysismentioning

confidence: 99%

Transdermal iontophoresis as an in-vivo technique for studying microvascular physiology

Tesselaar

Sjöberg

2011

Microvascular Research

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“…(7), the response R(t) is determined by the differential equation (2a) or (2b) together with the initial value given by Eq. (9). We shall show that in the models I and IV, the response decreases monotonically after administration, reaches a minimum, and then increases monotonically to the initial state R 0 .…”

Section: Turnover Modelsmentioning

confidence: 79%

“…What is left, as a potential source of this peak-shift, is then the drug mechanism function. Simulations have shown that a peak shift may or may not occur with increasing doses, and that they can be toward earlier as well as later times (Gabrielsson and Wiener (9)). The aim of this paper is to cast light on this phenomenon from a mathematical analytical point of view and to make general statements about the dynamics that may be useful for model discrimination and experimental design purposes.…”

Section: Introductionmentioning

confidence: 99%

A Dynamical Systems Analysis of the Indirect Response Model with Special Emphasis on Time to Peak Response

Peletier

Gabrielsson

Haag³

2005

J Pharmacokinet Pharmacodyn

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In this paper we present a mathematical analysis of the four classical indirect response models. We focus on characteristics such as the evolution of the response R(t) with time t, the time of maximal/minimal response T max and the area between the response and the baseline AU C R , and the way these quantities depend on the drug dose, the dynamic parameters such as E max and EC 50 and the ratio of the fractional turnover rate k out to the elimination rate constant k of drug in plasma. We find that depending on the model and on the drug mechanism function, T max may increase, decrease, decrease and then increase, or stay the same, as the drug dose is increased. This has important implications for using the shift in T max as a diagnostic tool in the selection of an appropriate model.

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“…For modelling of the enterohepatic circulation, data were fitted to model PK40 as previously described 6 . The model is illustrated in Fig.…”

Section: Pharmacokinetic Analysismentioning

confidence: 99%

The intravenous pharmacokinetics of diminazene in healthy dogs

Naidoo¹,

Mulders²,

Swan³

2009

J. S. Afr. Vet. Assoc.

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Diminazene remains one of South Africa's most commonly used antiprotozoal agents for the management of babesiosis in dogs . Although the drug has been on the market for over 40 years, its intravenous pharmacokinetics are poorly known. To better understand the pharmacokinetics of the drug Berenil®, it was reconstituted in sterile water and administered intravenously to 6 adult German shepherd dogs. All 6 dogs demonstrated the previously described secondary peak in the plasma concentration versus time profile. The plasma pharmacokinetics for diminazene are described by both non-compartmental and compartmental models. From non-compartmental analysis, the area under curve to the last sample point (AUClast), clearance (CL) and volume of distribution (Vz) were 4.65±1.95 ng/mℓ/h, 0.77±0.18 ℓ/kg/h and 2.28±0.60 ℓ/kg, respectively. For compartmental modelling, the plasma concentrations were fitted to both a 2-compartmental open model and a recirculatory enterohepatic model. From the recirculation model, the rate of release and re-entry into the central compartment varied markedly with the rate of release from the gall bladder (Ttom) being estimated at 27 ± 20.90 h. Once released, drug re-entry into the central compartment was variable at 9.70±5.48 h. With normal biliary excretion time being about 2 h, this indicates that the redistribution cannot be occurring physiologically from the bile. Although it was not possible to identify the site from which sequestration and delayed release is occurring, it is believed that it is most likely from the liver. The study therefore showed that the secondary peak described for the pharmacokinetics of intramuscular administered diminazene in the dog is not related to biphasic absorption

show abstract

Methodology for pharmacokinetic/pharmacodynamic data analysis

Cited by 173 publications

References 3 publications

Transdermal iontophoresis as an in-vivo technique for studying microvascular physiology

Transdermal iontophoresis as an in-vivo technique for studying microvascular physiology

A Dynamical Systems Analysis of the Indirect Response Model with Special Emphasis on Time to Peak Response

The intravenous pharmacokinetics of diminazene in healthy dogs

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