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Biomedical subjects

W C Shyu

Publications and source records attributed to W C Shyu.

At least 91 records · Page 5Linked to original sources
PubMed1990

Comparison of cefprozil and cefaclor pharmacokinetics and tissue penetration.

The pharmacokinetics and tissue penetration, as judged by skin blister fluid, of cefprozil and cefaclor were examined in 12 healthy male volunteers. Doses of 250 and 500 mg of each drug were given to fasting subjects in a crossover fashion. Serially obtained plasma, skin blister fluid, and urine samples were analyzed for cefprozil or cefaclor by validated high-pressure liquid chromatographic methods. After oral administration of 250 and 500 mg of cefprozil, mean concentrations in plasma rose to peak levels (Cmax) of 6.1 and 11.2 micrograms/ml, respectively, and those of cefaclor were 10.6 and 17.3 micrograms/ml, respectively. The elimination half-life of cefprozil (1.3 h) was significantly longer than that of cefaclor (0.6 h), and as a result, the area under the curve for cefprozil was about two times greater than that for cefaclor. Both cephalosporins were primarily excreted unchanged in urine. The mean skin blister Cmax values were 3.0 and 5.8 micrograms/ml for cefprozil and 3.6 and 6.5 micrograms/ml for cefaclor after the 250- and 500-mg oral doses, respectively. The mean Cmax values in skin blister fluid for both cephalosporins were comparable and were significantly lower than the corresponding Cmax values in plasma. However, the levels of cefprozil and cefaclor in skin blister fluid declined more slowly than they did in plasma. The skin blister fluid half-life estimates for cefprozil were significantly longer than they were for cefaclor. Parallel to the observation in plasma, the mean skin blister fluid areas under the curve for cefprozil were significantly higher than they were for cefaclor. The plasma and skin blister fluid pharmacokinetic analyses suggest that the exposure of humans to cefprozil is significantly greater than that to cefaclor at the same dose.

Administration, Oral↗
PubMed1990

Comparison of the effects of food on the pharmacokinetics of cefprozil and cefaclor.

The objective of this study was to assess the effects of food on the pharmacokinetics of cefprozil and cefaclor. A group of 12 healthy male volunteers received a single 250-mg dose of cefprozil or cefaclor under fasting conditions as well as after the intake of food. There was a 1-week washout period between each treatment. Serial blood samples were collected and assayed for cefprozil or cefaclor by specific high-pressure liquid chromatographic methods. The mean +/- standard deviation peak concentration (Cmax) of cefprozil in plasma was 6.13 +/- 1.22 micrograms/ml under the fasting condition and 5.27 +/- 1.06 micrograms/ml after breakfast, and these values were not significantly different from each other. The corresponding median time to reach Cmax was prolonged after food intake, but this difference was not significant. The mean Cmax values of cefaclor decreased significantly from 8.70 +/- 2.72 micrograms/ml under the fasting condition to 4.29 +/- 1.52 micrograms/ml after breakfast, and the corresponding median times to reach Cmax were significantly prolonged. The mean half-lives of cefprozil and cefaclor were nearly identical for the two treatments, suggesting that the elimination kinetics of these cephalosporins remained unaltered when the drugs were administered with food. The area under the plasma-concentration-versus-time curves for fasted and fed conditions were not significantly different for both drugs. The results of this study indicate that the extent of absorption and rate of elimination of both cephalosporins remain unaltered in the presence of food. However, the absorption rate of cefaclor is significantly reduced in the presence of food, while that of cefprozil remains unaltered. As a result, the Cmax of cefaclor is significantly reduced in the presence of food, whereas that of cefprozil is not significantly affected. Cefprozil can be administered with a meal without markedly affecting levels in blood.

Adult↗
PubMed1989

Prevalence and significance of intrahepatic hepatitis delta virus antigen expression in HBeAg-negative patients with chronic type-B hepatitis in Taiwan.

A consecutive series of 97 HBeAg-negative patients with chronic type-B hepatitis, who were not drug addicts or hemophiliacs, were examined for the prevalence of intrahepatic expression of hepatitis delta virus (HDV) antigen (HDAg) by direct immunofluorescence. The clinical and histological features were compared between those with and without intrahepatic HDAg expression. Intrahepatic HDAg expression was detected in 15 (15.5%) of the 97 patients. All of the 15 were males between 18 and 71 years of age. Each had elevated SGPT levels, with 46.8% being greater than 10 times normal and 73.4% greater than five times normal. Histological study revealed chronic lobular hepatitis in nine and chronic active hepatitis in six, including two with cirrhosis. Compared to the 82 patients without intrahepatic HDAg expression, no difference in the age (34.1 +/- 14.3 vs 36.7 +/- 10.8) and sex (15:0 vs 72:10) distribution was evident, but greater biochemical and histological activity was present in HDV-positive patients.

Adult↗
PubMed1989

Simple enzymatic determination of total cholesterol in gallstones.

In this simple method for rapid enzymatic determination of total cholesterol in human gallstones, gallstone powder is dissolved in an 80/20 by vol mixture of N,N-dimethylformamide and dimethyl sulfoxide and reacted directly with the aqueous enzymatic reagent, without further treatment. The organic solvents do not interfere with enzymatic activities of cholesterol oxidase, esterase, and peroxidase in the assay mixture. The method is reproducible (CVs 3.7% to 6.6%), analytical recoveries ranged from 98.6% to 102%, and linearity is good. Furthermore, results correlated well with those obtained by infrared spectroscopic measurements.

Cholelithiasis↗
PubMed1988

Effect of protein binding on drug penetration into blister fluid.

The effect of protein binding on drug penetration into blister fluid was evaluated by using cefonicid, ceftizoxime, and cefotaxime. Drug concentrations in a chamber with a high surface area/volume ratio (i.e., paper disk) follow changes in serum more closely than do those in a chamber with a low surface area/volume ratio. Both the area under the concentration-time curve ratio and the concentration ratio (by the disk method) for cefonicid were statistically lower than the ratios for ceftizoxime and cefotaxime. The high degree of protein binding of cefonicid results in the availability of less drug for diffusion to blister fluid than with the low-protein-binding ceftizoxime and cefotaxime.

Adult↗
PubMed1987

Pseudomonas peritonitis in neutropenic rats treated with amikacin, ceftazidime and ticarcillin, alone and in combination.

Peritonitis in neutropenic rats, caused by a strain of Pseudomonas aeruginosa resistant to amikacin and ticarcillin alone but susceptible to ceftazidime and combinations of amikacin with ticarcillin, amikacin with ceftazidime and ticarcillin with ceftazidime, was investigated. Four hours after a bacterial challenge with a LD70 intraperitoneal dose of P. aeruginosa (1.5 X 10(8) cfu/ml), either amikacin, ticarcillin, ceftazidime, amikacin-ticarcillin, amikacin-ceftazidime, or ticarcillin-ceftazidime was administered at dosing intervals that mimicked the serum concentrations of the drugs found in humans after therapeutic doses. When the serum concentrations did not exceed the MIC, as occurred with amikacin, no difference in survival was observed compared with controls. All other regimens resulted in animal survival during the treatment. When therapy was stopped only those regimens resulting in serum concentrations above the MBC were effective (amikacin-ticarcillin, amikacin-ceftazidime, ticarcillin-ceftazidime). The recovery of viable bacteria from the peritoneum agreed well with mortality.

Agranulocytosis↗
PubMed1987

High-pressure liquid chromatographic analysis of BMY-28142 in plasma and urine.

A high-pressure liquid chromatographic assay was developed for the quantitative analysis of a new cephalosporin, BMY-28142, in plasma and urine. The plasma method involved protein precipitation with acetonitrile and trichloroacetic acid followed by extraction of the acetonitrile into dichloromethane. After centrifugation, the organic phase was discarded, the aqueous solution was injected into a reverse-phase column, and peaks were detected at 280 nm. The urine method involved dilution of a urine sample with sodium acetate buffer (pH 4.25) and direct injection into the high-pressure liquid chromatography system. The assay validation data indicate that the assays for BMY-28142 in plasma and urine were specific, accurate, and reproducible. The analytical methods were applied to the determination of protein binding in human serum and to a pharmacokinetic study in rats. The results of the protein-binding study indicated that BMY-28142 was 16.3% bound to human serum proteins. In the pharmacokinetic study in rats, the maximum level in plasma of 38.7 micrograms/ml was achieved at 2.33 h after administration of a subcutaneous dose of 100 mg/kg. The levels in the plasma then declined with an elimination half-life of about 0.56 h. The mean values for the steady-state volume of distribution and total body clearance were 0.46 liters/kg and 11.9 ml/min per kg, respectively. The 0- to 24-h excretion of intact BMY-28142 in urine accounted for 88.6% of the dose.

Animals↗
PubMed1987

Pharmacokinetics of the novel cephalosporin cefepime (BMY-28142) in rats and monkeys.

The disposition of the novel cephalosporin cefepime (BMY-28142) was characterized for intravenous administration of single doses to rats and cynomolgus monkeys, the species used most extensively for safety evaluation of the compound. Serial blood samples were collected from individual animals, and plasma was analyzed for intact cefepime by a high-pressure liquid chromatography-UV method. Assay results were evaluated by compartmental and noncompartmental methods to characterize pharmacokinetics for each species and dosage regimen. For intravenous (i.v.) bolus administration of 28 to 386 mg/kg (body weight) to rats, total body clearance (CL; 11.0 ml/min per kg) was essentially invariant with the dose; however, the terminal half-life (t1/2) and the steady-state distribution volume (Vss) increased with increasing dose level. After administration of 87 to 1,502 mg/kg by i.v. infusion, CL (12.5 ml/min per kg) was again similar for all dose groups. Mean t1/2 values (1.3 to 4.6 h) appeared unusually long for a cephalosporin in rats, and inordinately variable. No consistent differences among dose group mean Vss values were found. The maximal concentration of drug in plasma at the end of infusion was not a linear function of dose. For the cynomolgus monkey, kinetic parameters for 5-min i.v. infusions were linearly related to dose over the range of 10 to 600 mg/kg. Mean parameter values were t1/2 = 1.7 h, CL = 1.6 ml/min per kg, and Vss = 0.21 liters/kg. The pharmacokinetic results indicate substantive differences between the two species with respect to their response to toxicologic doses of cefepime.

Analysis of Variance↗
PubMed1987

Effect of mucin on the pharmacokinetics of antibiotics in the rat.

The intramuscular pharmacokinetics of ticarcillin and amikacin in rats receiving 1 ml of 5% mucin suspension (equivalent to 250 mg/kg) administered intraperitoneally were not altered compared with the control animals. However, it is important to investigate the effect of mucin on the pharmacokinetics of antimicrobial agents in animals which are used to evaluate the efficacy of the agents.

Amikacin↗
PubMed1986

Pharmacokinetics of morphine and its surrogates. VIII: Naloxone and naloxone conjugate pharmacokinetics in dogs as a function of dose and as affected by simultaneously administered morphine.

Reversed-phase HPLC assays with electrochemical detection, developed to quantify naloxone, 6 beta-naloxol, and their hydrolyzed conjugates in biological fluids provided assay sensitivities of 10 to 20 ng/mL in plasma, urine, and bile. These fluids were monitored in dogs after iv bolus administrations of 0.47 and 4.7 mg/kg of naloxone. Plasma concentration-time data were well fitted by the sums of two exponentials with two sequential half-lives of 11 +/- 1 (SEM) and 56 +/- 3 min. Pharmacokinetics were dose-independent; total and renal clearances were 1334 +/- 133 mL/min and 42 +/- 9 mL/min, respectively, with a renal clearance of 65 +/- 5 mL/min for the conjugate. The percentage of the dose excreted in the urine as naloxone was 4.4 +/- 1.0%. There was a possible dose-dependent excretion of conjugate with 46 +/- 1 and 22 +/- 5% of the dose renally excreted at the high and low doses, respectively. In incomplete biliary cannulation, 13 and 18% were collected as conjugate in the bile of two bile-cannulated dogs. There was negligible biliary secretion of unchanged naloxone. Neither 6 beta-naloxol nor its conjugates were metabolites of naloxone in dogs. The simultaneous administration of naloxone does not reverse the dose-dependent pharmacokinetic perturbations of morphine. Morphine significantly lessened its own body, renal, and biliary clearances, as well as those of naloxone, and also lowered their apparent overall volumes of distribution. Plasma levels of naloxone and its conjugate were elevated with simultaneous morphine administration. Urinary flow rates were also greatly lessened and initial renal shut-down was implied at the higher morphine dose. Thus, the established competitive antagonistic action of naloxone on morphine does not extend to the reversal of the biological feedback effects of morphine on the metabolism and excretion of itself and simultaneously administered naloxone.

Animals↗
PubMed1986

Effect of saturable serum protein binding on the pharmacokinetics of unbound cefonicid in humans.

Previous studies have demonstrated high, concentration-dependent serum protein binding of cefonicid. To determine the in vivo pharmacokinetic significance of these observations, the pharmacokinetics of both total and unbound (non-protein-bound) cefonicid was studied in six volunteers after a single intravenous dose of 30 mg/kg. Saturable serum protein binding was observed in vivo; the mean +/- standard deviation free fraction of cefonicid was 17.6 +/- 6.1% immediately after administration and declined to a constant value of approximately 2% as total serum concentrations fell below 100 micrograms/ml. This nonlinear binding was associated with a pronounced decline in unbound serum cefonicid concentrations during the first 3 h after administration, with low or undetectable unbound drug concentrations by 12 h. Renal clearance of total cefonicid averaged 21.1 ml/min per kg and did not vary with time; in contrast, the mean +/- standard deviation unbound cefonicid renal clearance increased from 5.7 +/- 2.1 to 10.8 +/- 1.6 ml/min per kg with time (P less than 0.02). This study may partially explain the poor results obtained with single daily dosing of cefonicid in endocarditis. Dosage regimens of certain antimicrobial agents with high, saturable serum protein binding and extensive renal tubular secretion may be most appropriately designed based on unbound drug pharmacokinetics.

Adult↗
PubMedDate not supplied

High-performance liquid chromatographic-ultraviolet assay for the simultaneous quantitation of BMS-181101 and its putative hydroxy metabolites in rat and monkey plasma.

A specific, accurate, precise, and reproducible High-performance liquid chromatographic-Ultraviolet (HPLC-UV) method was developed for the simultaneous quantitation of BMS-181101 (I), a new antidepressant, and its putative metabolites, 6'-hydroxy (II) and 7'-hydroxy (III) of BMS-181101 in rat and monkey plasma. The assay procedure involved solid-phase extraction of the three analytes and the internal standard (IS; BMY-42568) on 1 mL Bond Elut CN cartridge using an automated solid phase extraction controller (ASPEC) system. The final elution of the analytes was performed using 0.25% triethylamine in methanol. The eluate mixture was evaporated to dryness, the residue was reconstituted in the mobile phase and injected onto a Zorbax Phenyl column (4.6 x 250 mm; 5 microns) at a flow-rate of 1.2 mL/min. The mobile phase consisted of 20% acetonitrile, 10% methanol, 69% water and 1% 1.0 M ammonium phosphate and 1.0 M tetramethylammonium hydroxide mixture adjusted to pH 3 by phosphoric acid. An ultraviolet absorbance detector set at 287 nm was used to detect the analytes. The nominal retention times were 5, 8, 15, and 18 min for II, III, I, and IS, respectively. The standard curves for the three analytes were linear in the concentration range of 50-1000 ng/mL. The lower limit of quantitation was 50 ng/mL for each analyte. The analyses of quality control (QC) samples indicated that the nominal values could be predicted with an accuracy of (+/-) 10.5% for all three analytes in rat and monkey plasma. The precision values of the QC samples for all three analytes were within 12.7% RSD for rat and monkey plasma. All three analytes and the IS were stable in the autosampler for at least 38 h; freeze/thaw stability of the 3 analytes was established for three cycles. Stability of BMS-181101 was established for one month at -20 degrees C. The application of the assay to a pharmacokinetic study in monkey is described.

Animals↗
PubMedDate not supplied

Gas chromatographic determination of enantiomers as diastereomers following pre-column derivatization and applications to pharmacokinetic studies: a review.

The introduction of chiral chromatographic methods has revolutionized the art of separation and quantitation of chiral drugs in biological fluids. A large number of chiral derivatization reagents for various functional groups are available commercially. Therefore, pre-column derivatization methods have become attractive and simple for the gas chromatographic assays in biological fluids. The intent of this article is to review the pre-column chiral derivatization reagents employed in gas chromatographic separations and analyses of enantiomers. A discussion of numerous procedures necessary to develop a quantitative gas chromatographic assay method for drug enantiomers is presented. In this regard, quantitative gas chromatographic assays based on this approach have been applied to investigate the stereoselective pharmacokinetics of several chiral drugs such as fenfluramine, norfenfluramine, methylphenidate, etodolac, propranolol, suprofen and methoxyphenamine.

Animals↗
PubMedDate not supplied

High-performance liquid chromatographic assay for the quantitation of nadolol in human plasma using fluorescence detection.

A rapid and sensitive HPLC-fluorescence assay was developed and validated for the determination of nadolol, a beta-blocker, in human plasma. Nadolol and the internal standard (desmethyl nadolol) were extracted from alkalinized plasma into methyl-tert.-butyl ether. The organic solvent was evaporated under nitrogen at 40 degrees C. The residue was reconstituted in the mobile phase and injected on to a C18 silica column (25 cm x 4.6 mm i.d.) at a flow rate of 1.4 mL/min. The mobile phase was 0.05 M monobasic ammonium phosphate (pH 4.2) and acetonitrile (84: 16, v/v). Fluorimetric detection was performed at excitation 230 nm and emission 330 nm. The nominal retention times were 3.3 and 4.3 min for the internal standard and nadolol, respectively. The lower limit of quantitation was 5 ng/mL and linearity (R2 > or = 0.994) of the standard curve was demonstrated between 5 and 500 ng/mL. The analysis of quality control (QC) samples at 60, 200 and 400 ng/mL resulted in precision estimates < or = 7.0% relative standard deviation (RSD) for the inter-assay and < or = 6.3% RSD for intra-assay. The predicted concentrations of the QC samples deviated < 10% from the nominal values. The extraction recovery of nadolol from human plasma was 64%. Nadolol was stable in human plasma at -20 degrees C for at least 5 months and for at least three freeze-thaw cycles. Nadolol and the internal standard were stable in the autosampler at 5 degrees C for at least 40 h. Overall, the assay was accurate, precise, sensitive, specific, and reproducible for the analysis of nadolol in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

Stereoselective analysis of nadolol in human plasma.

A stereoselective method, involving a single liquid-liquid extraction step, was developed and validated for the analysis of nadolol in human plasma. The assay involved extraction of nadolol and desmethyl-nadolol (as internal standard (IS)) from alkalinized plasma into dichloromethane. The organic solvent was separated and evaporated under nitrogen at 40 degrees C. A chiral derivatization scheme with (R)-(-)-napthylethylisocyanate (50 microL of 0.1% solution in dichloromethane for 60 min) was employed to convert the enantiomers of nadolol into the corresponding diastereomeric derivatives. The residue was reconstituted in the mobile phase and injected onto a C-18 column. The mobile phase was a mixture of methanol:tetrahydrofuran:water (52:7:41 by vol) containing about 0.001% v/v of both phosphoric acid and tetramethylethylenediamine. Fluorimetric detection was performed at excitation 230 and emission 330 nm. The assay was specific for the enantiomers of nadolol and the lower limit of quantitation was 2 ng/mL for each of the enantiomers. Analysis of quality control samples resulted in precision estimates of 7% RSD for inter-assay and 10.1% RSD for intra-assay and the predicted concentrations deviated less than 9.4% of the nominal values for the four enantiomers. The extraction recoveries of the individual enantiomer was about 70%. Stability of nadolol enantiomers were established for four freeze/thaw cycle periods and in the autosampler at 5 degrees C for at least 116 h.

Adrenergic beta-Antagonists↗