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Patrick J Faustino

Publications and source records attributed to Patrick J Faustino.

5 recordsLinked to original sources
PubMed2006

Validation of an in vitro method for the determination of cyanide release from ferric-hexacyanoferrate: Prussian blue.

Prussian blue (PB), ferric hexacyanoferrate, Fe(4)[Fe(CN)(6)](3) is indicated for the treatment of known or suspected internal contamination with radioactive cesium, radioactive thallium, or non-radioactive thallium. Owing to the molecular properties, cyanide is likely dissociated from PB under physiologically relevant pH conditions, thus raising a concern for the safety of the product. The objective of this study was to calibrate and validate a cyanide assay over a wide pH range (from 0.5 to 12) on the basis of Spectroquant cyanide test method (Merck). Merck's photometric method requires that the measurement solution be within pH 5.5-6.0, hence samples and standards need to be adjusted to this pH range. Since the process of pH adjustment may have significant impact on the determination of cyanide, the analysis method needs to be optimized, calibrated and validated under each pH condition in the study. The validation characteristics included accuracy, precision, quantification limit, linearity, and stability. The intra-day accuracy ranged from 90% to 109% for the deionized water and solutions of pH 0.5-12. The intra-day precision (R.S.D.) ranged from 2.4% to 8.1% for the deionized water and solutions of pH 0.5-12. The analytical range was linear from 0.05 to 0.5 ppm (mg/L). The R(2) ranged from 0.9925 to 0.9998. This validated method was successfully implemented to determine cyanide release from PB under various pH conditions (from 1.0 to 12) at different time-points (from 1 to 24 h).

Cyanides↗
PubMed2005

Determination of plasma and brain levels of isotretinoin in mice following single oral dose by high-performance liquid chromatography.

An isocratic reversed-phase high-performance liquid chromatographic method was established and validated according to FDA's Guidance for Industry, "Bioanalytical Method Validation", for the determination of isotretinoin in plasma and brain tissue from mice following single and multiple oral doses of Accutane. Plasma sample preparation included deproteination with acetonitrile-perchloric acid followed by centrifugation. Brain tissue was homogenized and extracted with acetonitrile-perchloric acid followed by centrifugation. The supernatants were analyzed by high-performance liquid chromatography (HPLC). Benz[alpha]anthrancene-7,12-dione was used as the internal standard. Chromatographic separation was achieved on a C18 column using an acetonitrile-aqueous 0.5% acetic acid (85:15, v/v) elution. The average extraction efficiency was >95% for plasma and >82% for brain. The lower limit of quantification was 30 ng/mL for plasma and was 30 ng/0.1g for brain tissue, respectively. The linear range for plasma was 30-600 ng/mL, and 15-300 ng/0.1g for brain. Maximum concentrations of isotretinoin in both plasma and brain were observed at 1h after single oral dosing (25 mg/kg). The maximum concentrations in plasma and brain were 2.36 microg/mL and 0.34 microg/g, respectively. The mean area under curve (AUC) in plasma was 6.13 microg h/mL. The mean eliminate half-life in plasma was estimated as 46 min.

Administration, Oral↗
PubMedDate not supplied

The effect of food on the relative bioavailability of rapidly dissolving immediate-release solid oral products containing highly soluble drugs.

The purpose of this study is to test the hypothesis that rapidly dissolving immediate-release (IR) solid oral products containing a highly soluble and highly permeable drug [biopharmaceutical classification system (BCS) class I] are bioequivalent under fed conditions. Metoprolol and propranolol (BCS class I) as well as hydrochlorothiazide (BCS class III) were selected as model drugs. The relative bioavailability of two FDA approved (Orange Book AB rating) solid oral dosage forms of metoprolol and propranolol/hydrochlorothiazide (combination tablets) was evaluated in human volunteers under fed conditions using a two-way crossover design. Equal numbers of male and female volunteers were recruited, and racial and/or ethnic minorities were not excluded. The plasma concentrations of metoprolol, propranolol, and hydrochlorothiazide were determined using validated high-performance liquid chromatography (HPLC) methods. Eighteen subjects completed the metoprolol study while 17 subjects completed the propranolol/hydrochlorothiazide combination tablet study. In the metoprolol study, the 90% confidence intervals of Cmax and AUC(inf) were 98-118% and 92-115%, respectively. For propranolol, the 90% confidence intervals of Cmax and AUC(inf) were 91-121% and 89-117%, and for hydrochlorothiazide, the 90% confidence intervals for Cmax and AUC(inf) were 96-107% and 97-106%, respectively. These study results appear to support the hypothesis that rapidly dissolving IR solid oral products containing a BCS class I drug are likely to be bioequivalent under fed conditions. In addition, BCS class III drugs may have the potential to be bioequivalent under fed conditions.

Administration, Oral↗
PubMedDate not supplied

Effects of amitriptyline and fluoxetine upon the in vitro proliferation of tumor cell lines.

Previous publications have suggested that commonly prescribed antidepressants have the potential to stimulate the proliferation of extant tumors in human and rodent in vivo and in vitro models. The direct effects of amitriptyline and fluoxetine were evaluated in assays that detect different aspects of proliferative responses at pharmacologically relevant drug concentrations. Three in vitro assays of cellular proliferation and clonal growth were used with human (MCF7, PA-1 and LS174T) and murine (B16.f10, C-3 and B16.f1) tumor cell lines. The cells were exposed to amitriptyline or fluoxetine (0.001-100 microM) for different time periods (1-7 days) and at varying serum concentrations (0.1-15%). Amitriptyline and fluoxetine failed to significantly stimulate tumor cell proliferation, DNA synthesis, or colony formation. Both drugs inhibited B16.f10 colony growth at concentrations above 5 microM along with significant suppression of DNA synthesis in B16.f10 and C-3 cells at 30 microM. Although there were generally no effects on cell proliferation by the drugs in the microtiter tetrazolium assay, several rare instances of stimulation were noted. Amitriptyline and fluoxetine were consistent in their lack of effect or inhibition with the human or murine tumor cell lines in conventional in vitro assays of cell proliferation and clonogenicity in optimal or suboptimal culture conditions.

Amitriptyline↗