Clinical Pharmacokinetics of Doxorubicin

Speth, P. A. J.; Hoesel, Q.G.C.M. van; Haanen, C.

doi:10.2165/00003088-198815010-00002

Cited by 344 publications

(240 citation statements)

References 74 publications

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“…The effective intracellular anthracycline concentration. which is in the JiM range (Speth et al 1988). should easily be reached by higher and more frequent dosing.…”

Section: Discussionmentioning

confidence: 99%

Low-density lipoprotein receptor-mediated delivery of a lipophilic daunorubicin derivative to B16 tumours in mice using apolipoprotein E-enriched liposomes

Versluis¹,

Rensen²,

Rump³

et al. 1998

Br J Cancer

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Summary Many tumours express relatively high levels of low-density lipoprotein (LDL) receptors on their membranes. The LDL receptor is, therefore, an attractive target for the selective delivery of antineoplastic drugs to tumour cells. We reported previously on the synthesis of small apolipoprotein E (apoE)-containing liposomes that behave in vivo in a very similar way to native LDL. In this study, we (LAD). Tissue distribution studies showed that LAD-loaded apoE liposomes were taken up and processed by the major LDL receptor-expressing organs (i.e. adrenals, liver and spleen). Of all other tissues, the tumour showed the highest uptake. The distribution pattems of LAD-loaded apoE liposomes and native LDL in the tumour-bearing mice were very similar, which supports the role of the LDL receptor in the disposition of the prodrug-loaded particles. The disposition of LAD followed the pattem of the liposomal carrier. We conclude that apoE liposomes enable LDL receptor-mediated specific delivery of antineoplastic (pro)

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“…The effective intracellular anthracycline concentration. which is in the JiM range (Speth et al 1988). should easily be reached by higher and more frequent dosing.…”

Section: Discussionmentioning

confidence: 99%

Low-density lipoprotein receptor-mediated delivery of a lipophilic daunorubicin derivative to B16 tumours in mice using apolipoprotein E-enriched liposomes

Versluis¹,

Rensen²,

Rump³

et al. 1998

Br J Cancer

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“…The clinical pharmacokinetics of doxorubicin are well characterized in the literature [28]. Doxorubicin concentrations are known to decay in a tri-exponential manner following intravenous (IV) bolus or infusion and typical parameters are available in the literature (e.g.…”

Section: Pharmacokinetic Profilesmentioning

confidence: 99%

Mathematical and computational models of drug transport in tumours

Groh

Hubbard

Jones

et al. 2014

J. R. Soc. Interface.

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The ability to predict how far a drug will penetrate into the tumour microenvironment within its pharmacokinetic (PK) lifespan would provide valuable information about therapeutic response. As the PK profile is directly related to the route and schedule of drug administration, an in silico tool that can predict the drug administration schedule that results in optimal drug delivery to tumours would streamline clinical trial design. This paper investigates the application of mathematical and computational modelling techniques to help improve our understanding of the fundamental mechanisms underlying drug delivery, and compares the performance of a simple model with more complex approaches. Three models of drug transport are developed, all based on the same drug binding model and parametrized by bespoke in vitro experiments. Their predictions, compared for a 'tumour cord' geometry, are qualitatively and quantitatively similar. We assess the effect of varying the PK profile of the supplied drug, and the binding affinity of the drug to tumour cells, on the concentration of drug reaching cells and the accumulated exposure of cells to drug at arbitrary distances from a supplying blood vessel. This is a contribution towards developing a useful drug transport modelling tool for informing strategies for the treatment of tumour cells which are 'pharmacokinetically resistant' to chemotherapeutic strategies.

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“…Doxorubicin hydrochloride (DXR) is the most commonly used anthracycline and is one of the most active agents in the treatment of breast cancer. However, it sometimes causes cardiotoxicity, which could lead to congestive heart failure and death (Dresdale et al, 1983;Speth et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

Albumin-conjugated PEG liposome enhances tumor distribution of liposomal doxorubicin in rats

Yokoe

Sakuragi

Yamamoto

et al. 2008

International Journal of Pharmaceutics

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To evaluate the effect of coupling of recombinant human serum albumin (rHSA) onto the surface of poly(ethylene glycol)-modified liposome (PEG liposome) on the in-vivo disposition characteristics of liposomal doxorubicin (DXR), the pharmacokinetics and tissue distribution of DXR were evaluated after intravenous administration of rHSA-modified PEG (rHSA/PEG) liposomal DXR into tumor-bearing rats.rHSA/PEG liposome prepared using a hetero-bifunctional cross-linker, N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP), efficiently encapsulated DXR (over 95%). rHSA/PEG liposomal DXR showed longer blood-circulating property than PEG liposomal DXR and the hepatic and splenic clearances of rHSA/PEG liposomal DXR were significantly smaller than those of PEG liposomal DXR. It was also demonstrated that the disposition of DXR to the heart, one of the organs for DXR-related side-effects, was significantly smaller than free DXR. Furthermore, the tumor accumulation of rHSA/PEG liposomal DXR was significantly larger than that of PEG liposomal DXR. The "therapeutic index", a criterion for therapeutic outcome, for rHSA/PEG liposomal DXR was significantly higher than PEG liposomal DXR. These results clearly indicate that rHSA-conjugation onto the surface of PEG liposome would be a useful approach to increase the effectiveness and safety of PEG liposomal DXR.

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Clinical Pharmacokinetics of Doxorubicin

Cited by 344 publications

References 74 publications

Low-density lipoprotein receptor-mediated delivery of a lipophilic daunorubicin derivative to B16 tumours in mice using apolipoprotein E-enriched liposomes

Low-density lipoprotein receptor-mediated delivery of a lipophilic daunorubicin derivative to B16 tumours in mice using apolipoprotein E-enriched liposomes

Mathematical and computational models of drug transport in tumours

Albumin-conjugated PEG liposome enhances tumor distribution of liposomal doxorubicin in rats

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