Introduction to Pharmacometrics and Quantitative Pharmacology with an Emphasis on Physiologically Based Pharmacokinetics

Sy, Sherwin K. B.; Derendorf, Hartmut

doi:10.1007/978-1-4939-1304-6_1

Cited by 11 publications

(7 citation statements)

References 145 publications

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“…In order to establish a dose, activity and safety relationship for LYC, pharmacokinetic information is essential to better characterize whether LYC is a potential lead candidate compound for drug development (Sy et al ., ). For this purpose, a validated analytical method to quantify LYC in biological matrix is a crucial step prior to running pharmacokinetic studies.…”

Section: Introductionmentioning

confidence: 97%

Rapid and efficient method for the quantification of lychnopholide in rat plasma by liquid chromatography–tandem mass spectrometry for pharmacokinetic application

Silva

Sousa

Montanha

et al. 2016

Biomedical Chromatography

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Lychnopholide is a sesquiterpene lactone usually obtained from Lychnophora and Eremanthus species and has pharmacological activities that include anti-inflammatory and anti-tumor. Lychnopholide isolated from Eremanthus matogrossenssis was analyzed in this study. The aims of this study were to develop and validate an analytical methodology by LC-MS/MS and to quantify lychnopholide in rat plasma. Chromatographic separation was achieved on a C18 column using isocratic elution with the mobile phase consisting of methanol and water (containing 0.1% formic acid) at a flow rate of 0.4 mL/min. The detection was performed in multiple-reaction monitoring mode using electrospray ionization in positive mode. The method validation was performed in accordance with regulatory guidelines and the results met the acceptance criteria. The linear range of detection was 10-200 ng/mL (r > 0.9961). The intra- and inter-day assay variability were <6.2 and <11.7%, respectively. The extraction recovery was approximately 63% using liquid-liquid extraction with chloroform. Lychnopholide was detected in plasma up to 60 min after intravenous administration in rats. This rapid and sensitive method for the analysis of the sesquiterpene lactone lychnopholide in rat plasma can be applied to pharmacokinetic studies of this compound. Copyright © 2016 John Wiley & Sons, Ltd.

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Section: Introductionmentioning

confidence: 97%

Rapid and efficient method for the quantification of lychnopholide in rat plasma by liquid chromatography–tandem mass spectrometry for pharmacokinetic application

Silva

Sousa

Montanha

et al. 2016

Biomedical Chromatography

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“…PKs and distributions of the active compounds are important to establish a better posology, route, formulation optimization, and risk assessment. Physiologically based pharmacokinetic (PBPK) modelling is used to predict the absorption, distribution, metabolism, and excretion (ADME) of synthetic or natural chemical substances in humans and other nonclinical species [13]. The present study aimed to evaluate the PKs and pharmacodynamics of 5-MOP from B. gaudichaudii after intravenous bolus and oral administrations in rats and extrapolate its tissue distribution to humans by PBPK modelling.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics, Pharmacodynamics and Dermal Distribution of 5-Methoxypsoralen Based on a Physiologically Based Pharmacokinetic Model to Support Phytotherapy Using Brosimum gaudichaudii

Martins¹,

Fonseca³

et al. 2020

Planta Med

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The treatment of vitiligo includes the combination of psoralens and ultraviolet type A exposure. Psoralens belong to a group of natural furanocoumarins that cause the skin to become sensitive temporarily to ultraviolet type A. The aim of this study was to develop a physiologically based pharmacokinetic model of 5-MOP from Brosimum gaudichaudii to support psoralen and ultraviolet type A therapy. A study of rats was used to establish and validate rat tissue distribution. The same chemical-specific parameters used in the rat model were also employed in the human model to project human pharmacokinetics. The highest exposures in the rats were in the brain and skin. Following a single dose of 1.2 mg/kg 5-MOP in humans, the model predicted a maximum concentration of 20 ng/mL and an area under the curve of 125 ng.h/mL, matching clinical results. The half-maximum melanogenesis concentrations in B16F10 cells were 29.5, 18.5, 11.5, and 6.5 ng/mL for synthetic 5-MOP, synthetic 5-MOP with ultraviolet type A, B. gaudichaudii alone, and B. gaudichaudii plus ultraviolet type A, respectively. Physiologically based pharmacokinetic model prediction in humans supported a once-every-two-day regimen for optimal melanin production. This type of framework can be applied to support strategies for dose selection and to investigate the impact of drugs on melanocyte recovery.

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“…The approach taken in this study utilises a ‘bottom-up’ approach that combines physicochemical properties, intrinsic clearance and physiological system information to describe the population of interest with PBPK models [16]. A typical organ compartment depicted in Fig.…”

Section: Methodsmentioning

confidence: 99%

Effect of reducing the paediatric stavudine dose by half: A physiologically-based pharmacokinetic model

Malmberg

Matsushima

et al. 2015

International Journal of Antimicrobial Agents

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Owing to significant dose-related toxicity, the adult stavudine dose was reduced in 2007. The paediatric dose, however, has not been reduced. Although the intended paediatric dose is 1 mg/kg twice daily (b.i.d.), the current weight-band dosing approach results in a mean actual dose of 1.23 ± 0.47 mg/kg. Both efficacy and mitochondrial toxicity depend on the concentration of the intracellular metabolite stavudine triphosphate (d4T-TP). We simulated the effect of reducing the paediatric dose to 0.5 mg/kg. A physiologically-based pharmacokinetic model consisting of 13 tissue compartments plus a full ADAM model was used to describe the elimination of stavudine. The volume of distribution at steady-state and apparent oral clearance were simulated and the resulting AUC profile was compared with literature data in adult and paediatric populations. A biochemical reaction model was utilised to simulate intracellular d4T-TP levels for both the standard and proposed reduced paediatric doses. Simulated and observed exposure after oral dosing showed adequate agreement. Mean steady-state d4T-TP for 1.23 mg/kg b.i.d. was 27.9 (90% CI 27.0–28.9) fmol/106 cells, 25% higher than that achieved by the 40 mg adult dose. The 0.5 mg/kg dose resulted in d4T-TP of 13.2 (12.7–13.7) fmol/106 cells, slightly higher than the adult dose of 20 mg b.i.d. [11.5 (11.2–11.9) fmol/106 cells], which has excellent antiviral efficacy and substantially less toxicity. Current paediatric dosing may result in even higher d4T-TP than the original 40 mg adult dose. Halving the paediatric dose would significantly reduce the risk of mitochondrial toxicity without compromising antiviral efficacy.

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Introduction to Pharmacometrics and Quantitative Pharmacology with an Emphasis on Physiologically Based Pharmacokinetics

Cited by 11 publications

References 145 publications

Rapid and efficient method for the quantification of lychnopholide in rat plasma by liquid chromatography–tandem mass spectrometry for pharmacokinetic application

Rapid and efficient method for the quantification of lychnopholide in rat plasma by liquid chromatography–tandem mass spectrometry for pharmacokinetic application

Pharmacokinetics, Pharmacodynamics and Dermal Distribution of 5-Methoxypsoralen Based on a Physiologically Based Pharmacokinetic Model to Support Phytotherapy Using Brosimum gaudichaudii

Effect of reducing the paediatric stavudine dose by half: A physiologically-based pharmacokinetic model

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