In Vitro and Ex Vivo Evaluation of Methotrexate Removal by Different Sorbents Haemoperfusion

Giardino, Roberto; Fini, Milena; Giavaresi, Gianluca; Spighi, M; Faenza, Stefano; Orlandi, Maurizio; Florio, Mario Leonardo

doi:10.3109/10731199309117650

Cited by 4 publications

(2 citation statements)

References 5 publications

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“…There are several approaches to the general problem of dose limitation, two of which are fast removal of the excess drug shortly after administration and the specific release of the drug at the site of choice. More specifically, for CP, the first of these solutions would mean, for instance, to develop a highly specific extracorporeal drug adsorbent which will be part of a closed circuit: Through a vein leading to the tumor area, a high dose of CP is infused, the excess of which is led back through another vein to the extracorporeal CP adsorbent . And the second approach would mean implanting a CP-release device near the tumor, limiting the high-dose to a localized organ.…”

Section: Introductionmentioning

confidence: 99%

Adsorption/Desorption Characteristics of cis-Platin on Mercapto-Silylated Silica Surfaces

2001

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High-dose cancer treatment with cis-platin (CP, cis-[Pt(NH3)2Cl2]), although of therapeutic value, is limited by its toxicity. Fast removal of excess drug shortly after administration and site-specific drug release are potential partial solutions of this problem. As a first stage toward these solutions, several adsorption/desorption properties of CP have been determined and analyzed. The main adsorbent selected for this study was silica silylated with (3-mercaptopropyl)trimethoxysilane (MPTS). The properties of this mercapto-derivatized silica (SiSH) were compared with an organically modified silica sol−gel material (Ormosil) using MPTS as modifier and with nonderivatized silica (SiOH). Although Langmuirian at first glance, a more detailed analysis of the adsorption isotherm of the CP/SiSH system revealed a cooperative mechanism of adsorption, namely, an increase in adsorption affinity with coverage. This cooperativity was detected by employing a coverage-dependent adsorption-equilibrium constant. Active shifting of the adsorption equilibrium toward the desorption side was achieved with 2,3-dimercapto-1-propane sulfonic acid sodium salt in solution. On the basis of the differences in adsorption affinities between SiSH and SiOH, we demonstrated, we believe for the first time, the ability to achieve interparticle migration of an adsorbate (CP) from one matrix to another.

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Section: Introductionmentioning

confidence: 99%

Adsorption/Desorption Characteristics of cis-Platin on Mercapto-Silylated Silica Surfaces

2001

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“…A total of 1376 articles were identified after removal of duplicates. In the final analysis, 92 articles were included, including two in vitro experiments (174,175), four animal experiments (176 –179), 84 case reports and case series (24,35,88,90,126,163,170,171,180 –255), one pharmacokinetic modeling study (256), and one observational study (160). Although several articles were designed as pharmacokinetic studies in kidney failure patients (170,190,204,225,242), many participants in these studies developed methotrexate-associated toxicity and were included in case reports.…”

Section: Resultsmentioning

confidence: 99%

Extracorporeal Treatment for Methotrexate Poisoning

Ghannoum

Roberts

Goldfarb

et al. 2022

CJASN

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Methotrexate is used in the treatment of many malignancies, rheumatological diseases, and inflammatory bowel disease. Toxicity from use is associated with severe morbidity and mortality. Rescue treatments include intravenous hydration, folinic acid, and, in some centers, glucarpidase. We conducted systematic reviews of the literature following published EXtracorporeal TReatments In Poisoning (EXTRIP) methods to determine the utility of extracorporeal treatments in the management of methotrexate toxicity. The quality of the evidence and the strength of recommendations (either “strong” or “weak/conditional”) were graded according to the GRADE approach. A formal voting process using a modified Delphi method assessed the level of agreement between panelists on the final recommendations. A total of 92 articles met inclusion criteria. Toxicokinetic data were available on 90 patients (89 with impaired kidney function). Methotrexate was considered to be moderately dialyzable by intermittent hemodialysis. Data were available for clinical analysis on 109 patients (high-dose methotrexate [>0.5 g/m2]: 91 patients; low-dose [≤0.5 g/m2]: 18). Overall mortality in these publications was 19.5% and 26.7% in those with high-dose and low-dose methotrexate–related toxicity, respectively. Although one observational study reported lower mortality in patients treated with glucarpidase compared with those treated with hemodialysis, there were important limitations in the study. For patients with severe methotrexate toxicity receiving standard care, the EXTRIP workgroup: (1) suggested against extracorporeal treatments when glucarpidase is not administered; (2) recommended against extracorporeal treatments when glucarpidase is administered; and (3) recommended against extracorporeal treatments instead of administering glucarpidase. The quality of evidence for these recommendations was very low. Rationales for these recommendations included: (1) extracorporeal treatments mainly remove drugs in the intravascular compartment, whereas methotrexate rapidly distributes into cells; (2) extracorporeal treatments remove folinic acid; (3) in rare cases where fast removal of methotrexate is required, glucarpidase will outperform any extracorporeal treatment; and (4) extracorporeal treatments do not appear to reduce the incidence and magnitude of methotrexate toxicity.

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Comparison of Hemodialysis versus Hemoperfusion in the Clearance of High‐Dose Methotrexate in Pigs

et al. 1995

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To evaluate the different capabilities of hemo-perfusion (HP) and hemodialysis (HD) treatment in resolving the side effects during high-dose methotrexate (MTX) therapy, an experimental comparative study was done. Under general anesthesia, 12 female Large-White pigs, 35 +/- 5 kg body weight, underwent a bilateral renal vessel ligature to create an acute renal failure and avoid the physiologic elimination of MTX. An MTX i.v. infusion was performed using a dose of 12.5 g/m2 and for a specific time according to its pharmacokinetics. The animals were divided into 2 groups of 6 animals each and connected to the extracorporeal circuit; the first group was submitted to a 1-h HP with an anion exchange resin (Dow 1X-2, Dow Chemical) and the second group to 1-h HD with capillary polysulfone fibers (F6, Fresenius). Blood samples were taken at established intervals for hematological and biochemical evaluations. The results demonstrate a higher capability of HP treatment (P < 0.001) related to HD in MTX removal.

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In Vitro and Ex Vivo Evaluation of Methotrexate Removal by Different Sorbents Haemoperfusion

Cited by 4 publications

References 5 publications

Adsorption/Desorption Characteristics of cis-Platin on Mercapto-Silylated Silica Surfaces

Adsorption/Desorption Characteristics of cis-Platin on Mercapto-Silylated Silica Surfaces

Extracorporeal Treatment for Methotrexate Poisoning

Comparison of Hemodialysis versus Hemoperfusion in the Clearance of High‐Dose Methotrexate in Pigs

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