Pharmaceutical research
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Pharmaceutical research · Jul 2000
Injectable chemotherapeutic microspheres and glioma II: enhanced survival following implantation into deep inoperable tumors.
Delivery of chemotherapeutics using implantable, biodegradable polymers provides a potentially powerful method of treating brain tumors. The present studies examined the ability of injectable microspheres, formulated to release carboplatin or BCNU for 2-3 weeks, to enhance survival in a rodent model of deep, inoperable glioma. ⋯ Together, these data: (1) demonstrate that sustained delivery of chemotherapy in or near the tumor site is superior to equipotent bolus doses in inoperable tumors, (2) demonstrate that injection of sustained release microspheres into the tissue surrounding a growing tumor may provide superior effects over injections directly into the tumor mass, and (3) suggest that this approach may provide a useful means of selectively delivering chemotherapeutics to tumors or portions of tumors that cannot otherwise be treated with conventional surgical approaches.
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Pharmaceutical research · Jul 2000
Injectable chemotherapeutic microspheres and glioma I: enhanced survival following implantation into the cavity wall of debulked tumors.
Implantation of biodegradable polymers provides a powerful method to deliver high, sustained concentrations of chemotherapeutics to brain tumors. The present studies examined the ability of injectable polymeric microspheres, formulated to release carboplatin or BCNU for 2-3 weeks, to enhance survival in a rodent model of surgically-resected glioma. ⋯ These data demonstrate: (1) that sustained delivery of chemotherapy is superior to equipotent bolus doses following tumor resection, and (2) that direct injection of sustained release microspheres into the tissue surrounding a growing tumor mass may provide superior effects over injections into the surgical cavity. They also suggest that successful implementation of this approach in humans may require measures or circumstances that improve upon the limited spatial drug diffusion from the implantation site.
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Pharmaceutical research · Jun 2000
Pharmacokinetic-pharmacodynamic analysis of the EEG effect of alfentanil in rats following beta-funaltrexamine-induced mu-opioid receptor "knockdown" in vivo.
The objective of this investigation was to determine the influence of pre-treatment with the irreversible mu-opioid receptor antagonist beta-funaltrexamine (beta-FNA) on the pharmacokinetic-pharmacodynamic (PK/PD) relationship of alfentanil in rats. ⋯ This investigation confirms the validity of a previously postulated mechanism-based PK/PD model for the effect of synthetic opiates in rats.
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Pharmaceutical research · Aug 1999
Pharmacokinetics and tissue disposition in monkeys of an antisense oligonucleotide inhibitor of Ha-ras encapsulated in stealth liposomes.
This study examined the pharmacokinetics and tissue distribution of an antisense oligonucleotide ISIS 2503, formulated in stealth (pegylated) liposomes (encapsulated) or in phosphate-buffered saline (unencapsulated). ⋯ The data suggest that stealth liposomes protect ISIS 2503 from nucleases in blood and tissues, slow tissue uptake, and slow the rate of clearance from the systemic circulation. These attributes may make these formulations attractive for delivering oligonucleotides to sites with increased vasculature permeability such as tumors or sites of inflammation.
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Pharmaceutical research · Jun 1999
Relationship between etomidate plasma concentration and EEG effect in the rat.
The effect-plasma concentration relationship of etomidate was studied in the rat using electroencephalographic changes as a pharmacodynamic parameter. ⋯ The results of the present study show that the concentration-effect relationship of etomidate can be characterized in individual rats using aperiodic analysis in the 2.5-7.5 Hz frequency band of the EEG. This characterization can be very useful for studying the influence of diseases on the pharmacodynamics of etomidate in vivo.