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At least 127 records · Page 7Linked to original sources
PubMed1987

Drug stability guidelines for a continuous infusion chemotherapy program.

Recent technological advances in ambulatory infusion pumps, the development of safe long-term venous access devices, and the clinical advantages of the continuous infusion of chemotherapeutic agents have facilitated the delivery of ambulatory infusion chemotherapy. This method of therapy provides chemotherapeutic drug infusions over a period of several days, weeks, or months. Therefore, the antineoplastic drugs used must be chemically stable for the duration of the infusion. However, an extensive compilation of extended stability (greater than 24 hours) data of intravenous solutions containing antineoplastic drugs is lacking, and as such, pharmacy concerns have been significant. We have accumulated extended chemical stability data (greater than or equal to 90% of time zero concentration) based on literature surveys and manufacturer written correspondence. The accumulated data, presented herein, support the following minimum stability limits (in days) with regard to single and multiple drug admixtures stored in 60-ml polyvinylchloride (PVC) reservoir bags (Cormed, Medina, NY) at room temperature: cytarabine (8), cyclophosphamide (6), doxorubicin (14), epidoxorubicin (14), floxuridine (8), fluorouracil (14), methotrexate, mitomycin-C (14), cisplatin (14), thiotepa (7), vinblastine (8), methotrexate/fluorouracil (14), doxorubicin/vinblastine (8), doxorubicin/cyclophosphamide (7), fluorouracil/cyclophosphamide (7), and doxorubicin/vincristine (14).

Antineoplastic Agents↗
PubMed1991

Change in the heterogeneous distribution of tubulin isotypes in mitotic microtubules of the sea urchin egg by treatment with microtubule depolymerizing or stabilizing drugs.

In the mitotic sea urchin egg, the spindle microtubules were composed of different tubulin isotypes from those of astral microtubules using monoclonal antibodies [Oka et al. (1990) Cell Motil. Cytoskeleton, 16, 239-250]. Three of the antibodies, D2D6, DM1B, and YL1/2, were specific for spindle microtubules, astral microtubules and reactive with both microtubules, respectively. The mitotic sea urchin egg was treated with microtubule depolymerizing (colcemid and nocodazole) and stabilizing (hexylene glycol) drugs and change in the heterogeneous distribution of the tubulin isotypes was investigated by the immunofluorescence procedure using these three monoclonal anti-tubulin antibodies. We observed that: (1) the microtubule depolymerizing drugs caused quick depolymerization of most mitotic microtubules, and a small number of spindle microtubules remaining were stained with all three antibodies; (2) hexylene glycol induced many microtubules in the mitotic apparatus, which was stained with D2D6 but was not stained with DM1B; (3) hexylene glycol also induced a great number of miniasters in the cytoplasm, and they were stained with three antibodies. These results suggest that these drugs altered the distribution of tubulin isotypes in the mitotic microtubules during depolymerization or polymerization within a short time.

Animals↗
PubMedDate not supplied

[Effectiveness of ketotifen--a drug stabilizing mast cell membranes--in the treatment of chronic forms of Horton's headache].

The authors made an attempt at treating chronic cluster headache with ketotifen (Zaditen, Sandoz). The drug is the first known agent stabilizing the cell membrane of mast cells which may be taken orally. The treatment was administered to 15 patients giving the drug in doses of 1 mg thrice daily for 8 weeks. A very good therapeutic effect was achieved in 8 cases. Good effect was noticed in 5 cases. In 2 cases only slight improvement was obtained. Reduction in the number of headache attacks occured already in the first week of treatment and progressed gradually during 8 weeks of this treatment.

Adult↗
PubMed1998

Internal morphology of poly(D,L-lactide-co-glycolide) BCNU-loaded microspheres. Influence on drug stability.

The solvent extraction/evaporation process has been used to form poly(D,L-lactide-co-glycolide) (PLAGA) BCNU-loaded microspheres designed for use as intracranial controlled-release implants. Their actual payload could reach 25% with a 20-50 microns size distribution. Scanning electron microscopy showed that such carriers had a smooth surface and a spherical geometry. Differential scanning calorimetry analyses carried out on drug-loaded microspheres established that the PLAGA Tg was markedly shifted towards the low temperatures along with the disappearance of the BCNU melting endotherm. Annealing experiments performed at room temperature did not induce any change of the loaded microsphere DSC profiles. These features indicated that the BCNU acted as a plasticizer for the coating material and formed with it a solid solution. Similarly, stability of encapsulated BCNU was assessed in different conditions of storage. It appeared that drug degradation increased with temperature increase: 5.4, 8.8, 32.4 and 51.2% of decomposition after 3 month storage at -18, 4, room temperature (RT) and 37 degrees C respectively. Since the free drug was stable at 4 degrees C and experienced only 10.6% decomposition at RT during the same storage time, the state of solid solution involving the intimate mixing of the drug and the polyester in the matrix favors a progressive decomposition of BCNU. However, keeping the microspheres 6 months at -18 degrees C or 3 months at 4 degrees C prevents a loss of drug superior to 10%.

Antineoplastic Agents↗
PubMedDate not supplied

Directing quadruplex-stabilizing drugs to the telomere: synthesis and properties of acridine-oligonucleotide conjugates.

Conjugates containing quadruplex-stabilizing acridines linked to oligonucleotides that are complementary to the G-rich human telomere sequence were synthesized. Acylation of 3,6-diaminoacridine followed by two Michael reactions provided derivatives suitable for conjugation, which were coupled to resin-linked amine-modified oligonucleotides by activating the carboxyl group with pentafluorophenyl 4-nitrobenzenesulfonate. After deprotection with aqueous ammonia at room temperature, conjugates incorporating different acridines, linkers, and oligonucleotide sequences were obtained. These were tested for their ability to stabilize intramolecular DNA quadruplexes that are based on the human telomeric repeat sequence (GGGTTA)(n).

Acridines↗
PubMed1992

[Molecular interaction in pharmaceutical solution, solubilization, partition, and stability of drugs].

The pharmaceutical studies carried out by the author during 40 years were reviewed from the viewpoint of molecular interaction. Included subjects are: electrostatic interaction between drug ions, ion pair formation and its partition to organic phase, drug solubilization by adjuvants, partition of drugs between aqueous and micellar phases, cyclodextrin inclusions, human serum albumin binding and drug stability related to the esterase-like activity of the albumin, and oral liposome preparation of vitamin K1. The drug stabilities related to those molecular interactions were emphasized.

Drug Stability↗
PubMedDate not supplied

Formulation of BCNU-loaded microspheres: influence of drug stability and solubility on the design of the microencapsulation procedure.

The design of a microencapsulation procedure for the preparation of biodegradable BCNU-loaded microspheres used as intracerebral implants is the aim of this work. This approach will give sustained high local concentrations of the anti-tumour drug in the brain without the associated significant systemic toxicity. The microencapsulation technique used is a solvent-evaporation process based on the formation of an oil-in-water emulsion. The stability of BCNU in methylene chloride saturated with water and its high value of partition coefficient between methylene chloride and water justifies the selection of this organic solvent as the dispersed phase in the methodology. A spectrophotometric method for the quantification of BCNU in mixtures containing PLAGA is developed which allows the evaluation of drug photodecomposition. The volume of methylene chloride and the concentration of PVA in the external aqueous phase are the two variables that induce the largest variations of the microsphere size. The two main process parameters leading to the highest microencapsulation yield are the polymer concentration in the organic phase and the volume of the external aqueous phase; whereas the pH of the external aqueous phase and the use of co-solvents in the organic phase lead only to a small improvement in microsphere payload.

Antineoplastic Agents, Alkylating↗
PubMedDate not supplied

[Comparative evaluation of efficiency of transcutaneous laser irradiation of blood and membrane-stabilizing drug therapy in correction of cell metabolism in patients with acute pyelonephritis].

In patients with acute pyelonephritis, the efficiency has been studied of the blood transcutaneous laser irradiation and of the medicamentous membrane-stabilizing therapy, with n = 31 and n = 27 respectively. In the serous stage of acute pyelonephritis both methods appeared to be efficient while in the transitional stage it is the membrane-stabilizing therapy that has been shown to be superior to transcutaneous blood laser irradiation.

Acute Disease↗
PubMed1989

Arrest of replication forks by drug-stabilized topoisomerase I-DNA cleavable complexes as a mechanism of cell killing by camptothecin.

Camptothecin, which induces an unusual type of DNA damage by trapping cellular topoisomerase I on chromosomal DNA in the form of drug-enzyme-DNA cleavable complexes, inhibits DNA synthesis and specifically kills S-phase cells. Cotreatment of L1210 cells with aphidicolin, which is an inhibitor of replicative DNA polymerases, completely abolished camptothecin cytotoxicity, suggesting the involvement of DNA replication in camptothecin cytotoxicity. In order to study the role of DNA replication in drug action, a cell-free SV40 DNA replication system was used in the present study. Camptothecin inhibited SV40 DNA replication in this cell-free system only in the presence of topoisomerase I. Addition of excess purified calf thymus DNA topoisomerase I to this extract system in the presence of camptothecin resulted in severe inhibition of SV40 DNA replication and the accumulation of linearized replication products, which contained covalently bound DNA topoisomerase I. We propose that the collision between moving replication forks and camptothecin-stabilized topoisomerase I-DNA cleavable complexes results in fork arrest and possibly fork breakage, which are lethal to proliferating cells.

Animals↗
PubMed2003

Cellular signaling pathways affect the function of ribonucleotide reductase mRNA binding proteins: mRNA stabilization, drug resistance, and malignancy (Review).

Ribonucleotide reductase is an enzyme that is essential for DNA synthesis and repair. It is composed of 2 dimeric proteins called R1 and R2 that are both necessary for enzymatic activity that reduces ribonucleotides to deoxyribonucleotides. This is the rate-limiting reaction that provides a supply of precursors for DNA synthesis therefore it is essential for cell proliferation. The importance of understanding the complex regulation of ribonucleotide reductase is emphasized by observations that mechanisms controlling its expression and activity may be altered during malignant cell proliferation which leads to drug resistance, making it a useful target to develop chemotherapeutic compounds in the treatment of cancer. Expression studies with the R1 and R2 genes have provided evidence for a direct role for the components of ribonucleotide reductase in determining malignant potential. Ribonucleotide reductase is regulated by transcriptional activation of gene expression and post-transcriptional mechanisms that alter mRNA message stability. Post-transcriptional regulation of mRNA turnover plays an important role in modulating mRNA steady state levels and therefore directly influences gene expression. The 3'-untranslated region (UTR) of R1 and R2 messages contain sequences that are important in regulating gene expression through changes in message stability. Studies have found that mRNA message stability is mediated by growth factors, cytokines and tumor promoters. Several studies have elucidated signal transduction pathways of tumor promoters, TGF-beta and oxidation/reduction agents. This report reviews how knowledge of these signaling pathways is revealing new insights into how ribonucleotide reductase mRNA binding proteins are important in regulating cellular proliferation, drug resistance and malignancy.

3' Untranslated Regions↗
PubMed1980

Effect of some membrane stabilizing drugs on histamine-induced contraction of guinea pig ileum.

The effect of disodium cromoglycate (DSCG), pyridoxine and procaine on histamine-induced contraction of isolated guinea pig ileum was investigated. The antiallergic drug DSCG exerted a protective action on ileum against histamine either when it was present or after it was washed out. Procaine, a local anesthetic exerted a similar pharmacological action on ileum to that of DSCG. On the other hand, pyridoxine protected guinea pig ileum against histamine only when it was present in the bath and this effect quickly disappeared after removing of pyridoxine. The mechanism of action of both DSCG and procaine is discussed in relation to their membrane stabilizing effect and inhibition of calcium transport, whereas effect of pyridoxine resembled to some extent, the action of theophylline.

Animals↗
PubMed1999

Poisoning of topoisomerase I by an antitumor indolocarbazole drug: stabilization of topoisomerase I-DNA covalent complexes and specific inhibition of the protein kinase activity.

We have investigated the mechanism of topoisomerase I inhibition by an indolocarbazole derivative, R-3. The compound is cytotoxic to P388 leukemia cells, but not to P388CPT5 camptothecin-resistant cells having a deficient topoisomerase I. R-3 can behave both as a specific topoisomerase I inhibitor trapping the cleavable complexes and as a nonspecific inhibitor of a DNA-processing enzyme acting via DNA binding. In addition, the drug is a potent inhibitor of the kinase activity of topoisomerase I. Unlike camptothecin, R-3 completely inhibits the phosphorylation of SF2/ASF, a member of the SR protein family, in the absence of DNA. The inhibitory effect is also observed using mutant enzyme Y723F that lacks DNA cleavage/religation activity but does not affect phosphotransferase activity, indicating, therefore, that R-3 acts independently at both DNA cleavage and protein kinase sites. R-3 is the only compound known thus far that interferes specifically with the kinase activity of topoisomerase I and not with other kinases, such as protein kinase C and the cdc2 kinase. The study reinforces the view that topoisomerase I is a dual enzyme with a DNA cleavage site juxtaposed to a functionally independent kinase site and shows for the first time that indolocarbazole drugs can inhibit both the DNA cleavage/religation and kinase activities of the enzyme.

Animals↗
PubMed2004

Cell-type specific regulation of calreticulin and Bcl-2 expression by mood stabilizer drugs.

Recent studies in rat brain and cell cultures have demonstrated that expression of the peptide-folding chaperone protein calreticulin is increased by valproate treatment, while the anti-apoptotic Bcl-2 is increased by both lithium and valproate. We asked whether a similar pattern of regulation by these drugs is evident in human neuronal and glial cells. One-week treatment with 1 mM valproate induced a significant (90%) increase in calreticulin mRNA and protein levels in SVG, a glial cell line, but reduced its mRNA levels by 38% in hNT neuronal cells. Valproate also markedly increased Bcl-2 mRNA levels by 260%, but only in hNT neurons. In contrast, lithium had no significant effect in either cell type. Valproate-induced increases in calreticulin may therefore show glial specificity in humans, while changes in Bcl-2 levels may be neuron specific. These results highlight the cell model dependence of outcomes in molecular studies of mood stabilizer effects and the need for caution in interpreting findings in model systems.

Analysis of Variance↗
PubMed1990

[The early bicycle ergometry test in drug-stabilized patients with unstable angina pectoris--the correlation with coronary angiography].

The relation between the results of the early submaximal symptom-limited bicycle ergometry [correction of veloergometric] test and coronary angiography were examined in 127 patients with unstable angina pectoris stabilized by medicaments. In 19 (15.0%) patients the test was negative and in 108 (85%) patients the test was positive (angina pectoris and/or ST depression greater than or equal to 0.1 mV at 80 ms after the point J of the ECG). Between the results of the early bicycle ergometry [correction of veloergometric] test and the coronary angiography, performed soon after the test, there was a close correlation. By using strict criteria or a combination of criteria for assessment of residual ischemia the test can with great accuracy differentiate the patients with multivascular from those with monovascular disease or with healthy coronary vessels.

Adult↗
PubMed1990

[The early bicycle ergometry test in drug-stabilized patients with unstable angina pectoris; its risk and benefit].

The risk of an early submaximum symptom-limited bicycle ergometry [correction of veloergometric] test and its prognostic value up to the end of the first year since the onset of unstable angina pectoris were studied in 258 patients with unstable angina pectoris who had been stabilized by medicamentous treatment. During the bicycle ergometry [correction of veloergometric] test no serious complications were observed. In 22 patients (35.7%) the test was negative and in 166 patients (64.3%) it was positive (angina pectoris and/or horizontal ST depression greater than or equal to 0.1 mV at 80 ms from the point J). In the patients with a positive test the prognosis is statistically worse (death, acute myocardial infarction, aortocoronary bypass, relapse of the unstable angina pectoris and angina pectoris of III and IV functional class according to NYNA/than in the patients with a negative bicycle ergometry [correction of veloergometric] test. The early bicycle ergometry [correction of veloergometric] test is with a high sensitivity (92.6%) and a lower specificity (66.7%) in recognizing the patients with a poor prognosis. The total prognostic accuracy of the test is 80.2%. It classifies the patients with unstable angina pectoris into two groups: with favourable and poor prognosis and helps in the selection of patients for surgical treatment.

Adult↗