Pharmakokinetik von Cyclo-phosphamid, Adriamycin und Adramycin-Prodrug (HMR 1826) im ex-vivo-isolierten perfundierten humanen Lungenresektionsmodell (IHLP)1

Abstract

The ex-vivo isolated human lung perfusion model (IHLP) has proven to be an ideal scientific model for pharmacological investigations of human tumors as an intermediate step between cell culture and in-vivo situation without any disadvantage for the patient. The tumor-to-host interaction is completely saved in this model. However, first pass reactions of drugs in other organs must not play a role for the substances studied with the IHLP. The role and future applications of the isolated perfused human lung model for other indications is discussed.

Development of Albumin‐binding Doxorubicin Prodrugs that are Cleaved by Prostate‐specific Antigen

“…In recent years a number of low-and high-molecular-weight prodrugs with Doxorubicin have been developed that were designed to be cleaved by tumor-associated enzymes such as β-glucuronidase (HMR 1826) [13], PSA [8, 10, 14Ϫ17], to date unidentified peptidases (CPI-0004Na) [18], cathepsin B (PK1 Ϫ Doxorubicin conjugated with N-(2-hydroxypropyl) methacrylamide copolymer) [19], or MMP-2 (albumin-binding Doxorubicin prodrug) [3,20] (reviewed in [20]). …”

Implementation of an experimental isolated lung perfusion model on surgically resected human lobes

“…In that study, lung lobes were perfused for up to 180 minutes with whole blood and saline, which ultimately led to pronounced lung edema. Importantly, subsequent histologically examination of the tissue showed no interference of ILP on pathohistological grading and staging 31 . The model was first used to study pharmacokinetics and toxicity of anti-cancer drugs within the lungs 31,32 .…”

“…Importantly, subsequent histologically examination of the tissue showed no interference of ILP on pathohistological grading and staging 31 . The model was first used to study pharmacokinetics and toxicity of anti-cancer drugs within the lungs 31,32 . Although the feasibility of normothermic lung perfusion has been clearly demonstrated on porcine, murine and human lungs 33 , there is still a lack of highly reproducible and cost- but also resource-effective models.…”

Micellar electrokinetic capillary chromatography reveals differences in intracellular metabolism between liposomal and free doxorubicin treatment of human leukemia cells

“…Similar absolute amounts of metabolites for both drug delivery systems and higher relative abundance for the Doxil ® treated cells may be an indication that the enzymatic pathways involved in DOX metabolism are saturated under free DOX treatment [44]. It could also be that the majority of DOX metabolism is occurring in acidic organelles, as opposed to the cytosol as previously believed (e.g.…”