In vitro andin vivo evaluation of the tissue-to-blood partition coefficient for physiological pharmacokinetic models

Lin, Jiunn H.; Sugiyama, Yuichi; Awazu, Shoji; Hanano, Manabu

doi:10.1007/bf01062545

Cited by 142 publications

(52 citation statements)

References 15 publications

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“…There are studies reporting the correlation between tissue-to-blood partition coefficients in rats obtained in vitro and in vivo. However, different results and conclusions were reached by the authors; Paixao et al observed significant differences between these Kp values [139], whereas Lin et al found a good correlation between in vivo and in vitro Kp [140]. We aimed to review cardiac surgery and forensic medical studies to provide a reference for drug distribution in human cardiac tissue.…”

Section: Introductionmentioning

confidence: 98%

Plasma vs heart tissue concentration in humans – literature data analysis of drugs distribution

Tylutki

Polak

2015

Biopharm & Drug Disp

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ABSTRACT:Little is known about the uptake of drugs into the human heart, although it is of great importance nowadays, when science desires to predict tissue level behavior rather than to measure it. Although the drug concentration in cardiac tissue seems a better predictor for physiological and electrophysiological changes than its level in plasma, knowledge of this value is very limited. Tissue to plasma partition coefficients (Kp) come to rescue since they characterize the distribution of a drug among tissues as being one of the input parameters in physiologically based pharmacokinetic (PBPK) models. The article reviews cardiac surgery and forensic medical studies to provide a reference for drug concentrations in human cardiac tissue. Firstly, the focus is on whether a drug penetrates into heart tissue at a therapeutic level; the provided values refer to antibiotics, antifungals and anticancer drugs. Drugs that directly affect cardiomyocyte electrophysiology are another group of interest. Measured levels of amiodarone, digoxin, perhexiline and verapamil in different sites in human cardiac tissue where the compounds might meet ion channels, gives an insight into how these more lipophilic drugs penetrate the heart. Much data are derived from postmortem studies and they provide insight to the cardiac distribution of more than 200 drugs. The analysis depicts potential problems in defining the active concentration location, what may indirectly suggest multiple mechanisms involved in the drug distribution within the heart.

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Section: Introductionmentioning

confidence: 98%

Plasma vs heart tissue concentration in humans – literature data analysis of drugs distribution

Tylutki

Polak

2015

Biopharm & Drug Disp

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“…The clearances were calculated as follows: Clearance ϭ dose/AUC. The blood to tissue distributions were calculated as follows: AUC tissue /AUC blood (Lin et al, 1982). All the data are presented as mean Ϯ S.E.M.…”

Section: Methodsmentioning

confidence: 99%

Effect of Silibinin on the Pharmacokinetics of Pyrazinamide and Pyrazinoic Acid in Rats

Wu¹,

Tsai²

2007

Drug Metab Dispos

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ABSTRACT:Pyrazinamide (PZA) is widely used in combination with other drugs in chemotherapy for tuberculosis. However, the dose-related liver injury is the main adverse effect of PZA and its metabolite [pyrazinoic acid (PA)]. Silibinin is the main flavonoid extracted from milk thistle (Silybum marianum), and it displays hepatoprotective properties. This study investigates the pharmacokinetics of PZA and PA and their interaction with silibinin in rats. The parallel study design was divided into six groups: PZA alone, PZA ؉ long-term silibinin exposure, PZA ؉ concomitant short-term silibinin exposure, PA alone, PA ؉ long-term silibinin exposure, and PA ؉ concomitant short-term silibinin exposure groups. The results indicate that the distribution ratio of PZA from bile to blood [area under the curve (AUC) bile /AUC blood ] in the PZA ؉ long-term silibinin exposure and PZA ؉ concomitant short-term silibinin exposure groups was also not significantly different when compared with the PZA alone group. However, the bile-to-blood distribution ratio of PA was significantly decreased in the PA ؉ long-term silibinin exposure and the PA ؉ concomitant short-term silibinin exposure groups. On PZA administration, the blood, but not bile, levels of PA were markedly increased in the PZA ؉ long-term silibinin exposure and PZA ؉ concomitant short-term silibinin exposure groups, but the bile-to-blood ratio of PA was decreased. These results suggest that the excretion pathway of PA may be blocked by silibinin through xanthine oxidase and hepatobiliary excretion.

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“…The clearance (CL) and half-life (t 1/2 ) were calculated as follows: CL ϭ dose/AUC; t 1/2 ϭ 0.693/k (k is the elimination rate constant). The liver-to-blood or bile-to-blood distribution was calculated as follows: AUC liver or bile /AUC blood (Lin et al, 1982). All data were presented as mean Ϯ S.E.M.…”

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confidence: 99%

Hepatobiliary Excretion of Berberine

Tsai¹,

Tsai²

2004

Drug Metab Dispos

142

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This article is available online at http://dmd.aspetjournals.org ABSTRACT:Berberine is a bioactive herbal ingredient isolated from the roots and bark of Berberis aristata or Coptis chinensis. To investigate the detailed pharmacokinetics of berberine and its mechanisms of hepatobiliary excretion, an in vivo microdialysis coupled with highperformance liquid chromatography was performed. In the control group, rats received berberine alone; in the drug-treated group, 10 min before berberine administration, the rats were injected with cyclosporin A (CsA), a P-glycoprotein (P-gp) inhibitor; quinidine, both organic cation transport (OCT) and P-gp inhibitors; SKF-525A (proadifen), a cytochrome P450 inhibitor; and probenecid to inhibit the glucuronidation. The results indicate that berberine displays a linear pharmacokinetic phenomenon in the dosage range from 10 to 20 mg kg ؊1, since a proportional increase in the area under the concentration-time curve (AUC) of berberine was observed in this dosage range. Moreover, berberine was processed through hepatobiliary excretion against a concentration gradient based on the bile-to-blood distribution ratio (AUC bile /AUC blood ); the active berberine efflux might be affected by P-gp and OCT since coadministration of berberine and CsA or quinidine at the same dosage of 10 mg kg ؊1 significantly decreased the berberine amount in bile. In addition, berberine was metabolized in the liver with phase I demethylation and phase II glucuronidation, as identified by liquid chromatography/tandem mass spectrometry. Also, the phase I metabolism of berberine was partially reduced by SKF-525A treatment, but the phase II glucuronidation of berberine was not obviously affected by probenecid under the present study design.

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In vitro andin vivo evaluation of the tissue-to-blood partition coefficient for physiological pharmacokinetic models

Cited by 142 publications

References 15 publications

Plasma vs heart tissue concentration in humans – literature data analysis of drugs distribution

Plasma vs heart tissue concentration in humans – literature data analysis of drugs distribution

Effect of Silibinin on the Pharmacokinetics of Pyrazinamide and Pyrazinoic Acid in Rats

Hepatobiliary Excretion of Berberine

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