Biomedical subjects

Sung-Hoon Ahn

Publications and source records attributed to Sung-Hoon Ahn.

6 recordsLinked to original sources

PubMed2006

Quantification of clotiazepam in human plasma by gas chromatography-mass spectrometry.

An analytical procedure was developed and validated for the quantification of clotiazepam in human plasma. After subjecting plasma samples to solid-phase extraction, the extract was evaporated and the residue re-constituted. An aliquot of the mixture was injected onto a gas chromatography-mass spectrometry system. The detector response was linear for clotiazepam concentrations in the range of 5-200 ng/ml. Intra- and inter-day precision for the assay over the concentration range was below 13.1 and 13.5%, and the accuracy ranged between 99.0-107.9% and 92.4-101.3%, respectively. The drug was found to be stable under various processing conditions used. The method is applicable to human pharmacokinetic studies of clotiazepam.

Azepines↗

PubMed2006

Mechanism for increased bioavailability of tacrine in fasted rats.

The mechanism associated with the increased bioavailability of tacrine as a result of a 24-h period of fasting was examined in rats. The AUC value for tacrine after the fasting was 52% higher compared with normal feeding when 4 mg kg(-1) of tacrine was orally administered, but the value for velnacrine, a hydroxylated metabolite of tacrine, was reduced by 10%. The relative metabolic ratio of tacrine in urinary excretion (Au(tacrine) divided by Au(velnacrine)) was lower in fasted rats compared with normally fed rats. This clearly shows that metabolism of tacrine is reduced with 24-h fasting after oral administration. Altered intestinal permeation in the fasting state was hypothesized, and the transport of tacrine across the rat intestine was studied. When a fasted intestine was mounted in an Ussing chamber, the mucosal-to-serosal permeability of tacrine was increased to double that for a fed rat intestine. To examine the effect of absorption rate on the hepatic metabolism of tacrine, a direct pyloric vein infusion study was carried out. Compared with an infusion of tacrine for 5 min, a slow infusion of tacrine over a period of 30 or 60 min increased the hepatic metabolism of tacrine and decreased its systemic clearance in rats. Collectively, these results suggest that rapid transport across the intestine aids tacrine in avoiding hepatic first-pass metabolism and enhances its bioavailability in fasted rats. From these findings, we conclude that both oral administration before a meal and a reduction in the dose might be recommended in tacrine therapy considering the serious hepatotoxicity of tacrine in clinical use.

Administration, Oral↗

PubMed2006

Application of a sample pooling method for the accelerated assessment of the rate of uptake of drugs by the brain in rats.

The purpose of this study was to examine the feasibility of applying a sample pooling method to the accelerated estimation of the uptake clearance of drugs to the brain in rats. Brain uptake clearances (CL(uptake)) were estimated for five model compounds using the sample pooling method and an integration plot analysis. CL(uptake) was also evaluated for caffeine and theophylline by brain microdialysis. The parameters and throughput of the pooling method were compared with those of typically used standard methods. The correlation for CL(uptake) was statistically significant (P<0.005) between the integration plot and the current method; the throughput of evaluation was 15-fold higher for the sample pooling method. A comparison of CL(uptake) values indicated that the three methods showed comparable results for caffeine while the CL(uptake) of theophylline using the proposed method was significantly different from those of the other methods. A kinetic analysis indicated that a compound with a slower CL(uptake) and longer half-life (e.g., theophylline) is more prone to error and that the lower limit of the CL(uptake) of 0.17 mL min(-1) (g brain)(-1) may be set so as to have an error less than 20% of the estimation. These results suggest that the sample pooling method is applicable for use in the accelerated estimation of the uptake clearance of compounds in the brain for which the value is greater than 0.17 mL min(-1) (g brain)(-1).

Animals↗

PubMed2005

Comparison of pharmacokinetics of loxoprofen and its active metabolites after an intravenous, intramuscular, and oral administration of loxoprofen in rats: evidence for extrahepatic metabolism.

The objective of this study was to characterize the extent of the formation of the active (trans-alcohol form) and inactive (cis-alcohol) metabolites of loxoprofen and to compare the kinetics after its intragastric, intravenous, and intramuscular administrations in rats. After intravenous administration of the drug at doses of 5-20 mg/kg, the clearance and the volume of distribution for loxoprofen, and the ratios of the AUC for the metabolites to the parent drug were not statistically different with the dosage; the formation clearances were 1.08 and 0.87 mL/min/kg for the active and its isomeric metabolite, respectively. After the intragastric, intravenous, or intramuscular administration, AUC for loxoprofen and the metabolites at a dose of 10 mg/kg were not statistically different for the different routes of administration. The formation of the metabolites with the concomitant loss of loxoprofen was found in incubations with liver homogenates and blood but not with a muscle homogenate or plasma, indicating that the conversion of loxoprofen to the metabolites may occur both in the liver and extraheptic tissue(s). Thus, approximately 22% of the loxoprofen may have been converted to the active metabolite in the liver and the extraheptic tissue(s) and the pharmacokinetics of the active metabolite was independent of the route of administration.

Administration, Oral↗

PubMed2004

Pharmacokinetic characterization of dehydroevodiamine in the rat brain.

The objective of this study was to examine the kinetics of the distribution of dehydroevodiamine (DHED) in the rat brain. After an intravenous infusion of 15 min (dose of 1-10 mg/kg), the temporal profiles of the plasma levels of DHED declined in a multiexponential manner. Moment analysis indicated that the clearance and steady-state volume of distribution for DHED were not statistically different with the dose, indicating that the pharmacokinetics for DHED is linear in the range examined. Nonlinear regression analysis of DHED concentrations in the plasma and the brain revealed that the linear kinetics into and out from the brain reasonably described the data and that the clearances for influx into and efflux from the brain were comparable. Transport clearances for DHED across MBEC4 monolayers, an in vitro model of the blood-brain barrier, were also comparable for influx and efflux, and were independent of the medium concentration. The concentration of DHED in cerebrospinal fluid was negligible compared with that found in plasma, indicating that the drug is not primarily distributed to the brain via the blood-cerebrospinal fluid barrier. These observations indicate that DHED is transported from the systemic circulation to the brain via the blood-brain barrier by linear kinetics.

Algorithms↗

PubMed2002

Simple liquid chromatography-electrospray ionization mass spectrometry method for the routine determination of salmon calcitonin in serum.

A simple liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) method was developed for the quantification of salmon calcitonin (sCT) in serum. Serum samples from rats and dogs were deproteinized and freeze-dried. The residue was then reconstituted with 57% acetonitrile in water containing 0.1% trifluoroacetic acid and 0.005% benzalkonium chloride. A 20-microl aliquot of the reconstituted solution was injected onto a polymer based RP-C18 column, The outlet was connected to an ion-trap mass spectrometer equipped with an ESI source, and spectra were recorded in a positive-ion, selected-ion monitoring mode. The limit of quantification of the method was 10 ng/ml. Biexponential curves were observed for the temporal serum concentration of sCT following intravenous administration of sCT to rats (100 microg/kg) and dogs (250 microg/kg), resulting in reasonable pharmacokinetic parameters. The present method appears applicable to routine analysis of serum sCT in pharmacokinetic studies with good selectivity, accuracy and precision.

Animals↗