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Biomedical subjects

S A Stavchansky

Publications and source records attributed to S A Stavchansky.

11 recordsLinked to original sources
PubMed2006

Biowaiver monographs for immediate release solid oral dosage forms: acetaminophen (paracetamol).

Literature data are reviewed on the properties of acetaminophen (paracetamol) related to the biopharmaceutics classification system (BCS). According to the current BCS criteria, acetaminophen is BCS Class III compound. Differences in composition seldom, if ever, have an effect on the extent of absorption. However, some studies show differences in rate of absorption between brands and formulations. In particular, sodium bicarbonate, present in some drug products, was reported to give an increase in the rate of absorption, probably caused by an effect on gastric emptying. In view of Marketing Authorizations (MAs) given in a number of countries to acetaminophen drug products with rapid onset of action, it is concluded that differences in rate of absorption were considered therapeutically not relevant by the Health Authorities. Moreover, in view of its therapeutic use, its wide therapeutic index and its uncomplicated pharmacokinetic properties, in vitro dissolution data collected according to the relevant Guidances can be safely used for declaring bioequivalence (BE) of two acetaminophen formulations. Therefore, accepting a biowaiver for immediate release (IR) acetaminophen solid oral drug products is considered scientifically justified, if the test product contains only those excipients reported in this paper in their usual amounts and the test product is rapidly dissolving, as well as the test product fulfils the criterion of similarity of dissolution profiles to the reference product.

Acetaminophen↗
PubMed2001

Human endothelial cell response to gram-negative lipopolysaccharide assessed with cDNA microarrays.

To assess the feasibility of using cDNA microarrays to understand the response of endothelial cells to lipopolysaccharide (LPS) and to evaluate potentially beneficial agents in treatment of septic shock, human umbilical vein endothelial cells were exposed to Escherichia coli LPS for 1, 4, 7, 12, or 24 h. Total RNA was isolated and reverse-transcribed into (33)P-labeled cDNA probes that were hybridized to human GeneFilter microarrays containing approximately 4,000 genes. The mRNA levels of several genes known to respond to LPS changed after stimulation. In addition, a number of genes not previously implicated in the response of endothelial cells to LPS also appeared to be altered in expression. Nuclear factor-kappaB (NF-kappaB) was shown to play an important role in regulating genes identified from the microarray studies. Pretreatment of endothelial cells with a specific NF-kappaB translocation inhibitor eliminated most of the alterations in gene expression. Quantitative RT-PCR results independently confirmed the microarray results for monocyte chemotactic protein-1 and interleukin-8, and enzyme-linked immunosorbent assays demonstrated that augmented transcription was followed by translation and secretion.

Cells, Cultured↗
PubMed1982

A new subcutaneously-implantable reservoir for sustained release of nicotine in the rat.

A subcutaneously-implantable reservoir for the sustained release of nicotine is described. The device, dubbed INR for Implantable Nicotine Reservoir, is a small glass cup sealed with Silastic polymer. It releases 3.4 mg of nicotine per 24 hours. When implanted into moderately-sized female Sprague-Dawley rats it produces blood nicotine levels of 400-500 ng/ml which remain relatively stable over at least 18 days. INRs are nontoxic, reproducible, inexpensive, and adaptable for pharmacological and toxicological studies in rats and other small animals.

Animals↗
PubMed1979

Phenytoin cumulation kinetics.

Four male subjects were given phenytoin orally in single or twice-daily doses. Subjects were on 2 or 3 different dosing rates from 260 to 600 mg phenytoin sodium daily. Predose blood samples were obtained almost daily. The resulting serum levels, measured by gas-liquid chromatography, ranged from 1 to 18 micrograms/ml. Serum phenytoin concentration-time data were fit to a 1-compartment open model with zero-order input and Michaelis-Menten elimination. The resulting computer-generated parameter estimates (Vmax, 5.28 to 8.41 mg/kg/day; Km, 0.83 to 4.18 mg/1; Vd, 0.74 to 0.97 1/kg) are in agreement with the ranges of values in the literature. The time course of phenytoin cumulation is compatible with the presence of a major elimination pathway exhibiting Michaelis-Menten kinetic behavior.

Administration, Oral↗
PubMed1978

In vivo distribution of carbon-11 phenytoin and its major metabolite, and their use in scintigraphic imaging.

Curie quantities (0.3--1.5 Ci) of H11CN were used in the synthesis of C-11-tagged phenytoin (C-11.DPH) and 5-(p-hydroxyphenyl)-5-phenylhydantoin (C-11.HPPH), using a modified Bücherer-Bergs reaction. The H11CN was produced from a mixture of 95% nitrogen and 5% hydrogen by a 45-min bombardment with 10-MeV protons at 10 muA. Following i.v. infusions of C-11 DPH (13.7 mg/kg at a rate of 29 mg/min) into the left femoral vein of Rhesus monkeys, DPH shows persistent concentration in the brain and liver fields. Extravascular administration shows significant retention at the site of administration. Intravenous bolus injection of [11C]-HPPH into a Rhesus monkey, at a dose of 6.4 mg/kg, resulted in localization of this compound in the liver, gallbladder, urinary bladder, and intestinal fields. Loss of activity from the liver region, with appearance of this activity in the intestinal field, suggests that [11C]-HPPH is secreted into the intestine via the bile. Further investigation is needed to study the potential of [11C]-DPH as a brain-scanning agent and [11C]-HPPH as a possible cholescintigraphic agent.

Animals↗
PubMedDate not supplied

Human pharmacokinetics of ethynyl estradiol 3-sulfate and 17-sulfate.

Pharmacokinetic parameters of ethynyl estradiol 3-sulfate (EE-3) and 17-sulfate (EE-17) were estimated. Each sulfate was administered orally and intravenously to five ovariectomized volunteer women. Blood samples were taken over a period of 24 h. Radioimmunoassay for free and sulfoconjugated ethynyl estradiol (EE) was performed. The analysis of the plasma concentrations obtained after administration of EE-3 and EE-17 indicates significant differences in their pharmacokinetic profiles. EE-3 is cleared more rapidly from the central compartment (systemic circulation), which may indicate that differences in protein binding, tissue binding, metabolism, and distribution exist between EE-3 and EE-17. It has been suggested that these conjugates are a slow-release reservoir for maintenance of blood levels of free EE itself. However, previous studies in baboons have shown that the half-lives of the free and sulfoconjugated EE are similar (ranging from 8.8 to 11.2 h), which is not consistent with this hypothesis. The t1/2 beta (mean 9.28 h) of the 17-sulfate after IV administration was almost identical in women and baboons, and similar to the t1/2 beta of free EE, confirming the previous observation. Only 3.4% of IV and 11.4% of the orally administered 17-sulfate appeared in the blood as free EE; with the 3-sulfate, the conversions were 13.7 and 20.7%, respectively, suggesting that these sulfates are not important slow-release reservoirs. The similarity of pharmacokinetic parameters between women and baboons suggests that this species of nonhuman primate is, in important respects, a suitable animal model for clinical pharmacology.

Administration, Oral↗
PubMedDate not supplied

Kinetic and spectral studies of type I and type II compounds with rat hepatic microsomes in the presence of the major metabolite of diphenylhydantoin.

The nature of the inhibitory effects of the major metabolite of diphenylhydantoin, 5-(p-hydroxyphenyl)-5-phenylhydantoin (HPPH), on the in vitro metabolism of ethylmorphine and aniline by rat hepatic microsomes was examined. The N-demethylation of ethylmorphine was competitively inhibited by HPPH, whereas inhibition of the hydroxylation of aniline was not competitive. The spectrum produced by HPPH when added to microsomal suspensions does not resemble the classical type I or type II spectra, but rather a reversed type I spectrum. Spectral evidence is presented indicating that HPPH also diminishes the magnitude of the spectral change produced by type I and II compounds.

Aniline Compounds↗