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Biomedical subjects

K Chan

Publications and source records attributed to K Chan.

At least 253 records · Page 14Linked to original sources

Plasma concentration of pyridostigmine during the antagonism of neuromuscular block.

The plasma concentrations of pyridostigmine were measured in eight patients during the antagonism of non-depolarizing neuromuscular blockade. After the injection i.v. of pyridostigmine bromide 14.6 mg/70 kg, the concentration of the drug rapidly decreased between 2 and 7 min, and then declined more slowly. After 2 h, significant amounts of pyridostigmine were still present in the plasma of all subjects. In the eight patients studied, the initial half-life was 1.0 +/- 0.3 min and the terminal half-life was 46.4 +/- 6.5 min (mean +/- SEM). Total body clearance of pyridostigmine was 8.7 +/- 1.5 ml min-1 kg-1, and the total apparent volume of distribution was 536 +/- 80 ml kg-1. Possible explanations for the differences between these results and previous studies are considered.

Adult↗

Effect of antacids on the plasma concentration of phenoperidine.

The effect of antacids on the plasma concentration of phenoperidine was studied in six volunteers. All subjects received the same dose of phenoperidine (15 micrograms kg-1) on different occasions in the presence, and absence of, an antacid preparation. In control studies, secondary peaks in the plasma concentration of phenoperidine were invariably observed; these were entirely eliminated, or modified substantially, by the concurrent administration of antacids. In the latter conditions, plasma concentrations of phenoperidine were greater during the first 20 min, and the area under the plasma concentration--time curve between 0 and 20 min was significantly greater than in control studies. In contrast, the plasma clearance of the drug was almost identical in control conditions and during treatment with antacids. After the oral administration of phenoperidine to two subjects, the systemic bioavailability of the drug was 9.9% and 13.9% respectively.

Administration, Oral↗

Effect of urine pH on the elimination of phenoperidine.

The effect of urine pH on the plasma concentration and elimination of phenoperidine and its main metabolites was studied in six volunteers. The clearance of unchanged phenoperidine in acid urine was significantly greater than in neutral or alkaline urine. By contrast, the elimination of its basic metabolites was enhanced in uncontrolled or alkaline urine. Other pharmacokinetic parameters were not significantly affected.

Adult↗

The dissolution and oral bioavailability of mexiletine capsules modified for clinical trial. A preliminary report.

The dissolution and bioavailability of two preparations of mexiletine hydrochloride (200 mg), one available commercially as Mexitil and one modified by the Hospital Pharmacy for a clinical trial, were investigated in a cross-over study with healthy volunteer subjects. The evaluation of bioavailability was based on comparisons of the mean residence time (MRTp.o.) and mean absorption time (MATp.o.), areas under the plasma mexiletine concentration time-curve (AUC) and urinary recovery of unchanged mexiletine under controlled condition of acidic urinary pH after oral administration of single doses of either 400 mg or 200 mg as mexiletine hydrochloride. Three different methods of calculation were used to account for possible changes in clearance of the drug in between treatments. Bioavailability data were available from 3 cross-over studies as the investigation was terminated because one subject experienced idiosyncratic reactions to mexiletine. The mean-transit-time, T DISSOLVED-IN VITRO, for the hospital-modified capsules (2.8 min) was longer than that of the Mexitil capsule (2.0 min) in 0.1 HCl. This delay in dissolution was complemented by an increase in MATp.o. (0.43 and 0.58 hr respectively for Mexitil and hospital-modified capsules) obtained in one subject. The bioavailabilities of the two preparations were comparable from AUC between 0 to 6 hr, but the plasma curves from 6 to 48 hr were not followed. The mean times in vivo, T MEAN-IN VIVO (determined from urinary elimination curves in a cross-over study of 3 subjects) were consistently shorter after ingestion of Mexitil capsules though the significance was difficult to obtain due to small sample size.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The influence of urinary pH on the disposition of indomethacin in healthy volunteers.

The influence of urinary pH on the plasma levels and renal elimination of unchanged indomethacin has been studied in seven healthy volunteers with the use of a specific and sensitive gas-liquid chromatographic method assay for indomethacin in plasma and urine. There is a wide variation in the terminal t1/2 (2.5-10.3 h) and the AUC (5264-12693 ng/ml h) of indomethacin after a standard oral dose (50 mg) under 'normal' urinary condition. Such variation is probably, in part, due to an intersubject difference in extrarenal elimination of the drug. The urinary recovery of unchanged indomethacin is highest at alkaline pH (15.7 +/- 5.3%), lowest at acidic pH (3.5 +/- 2.0%) and the 'normal' value is 7.1 +/- 1.6%. These differences are statistically significant. Despite such influence there is no apparent change in plasma levels of the drug under uncontrolled and controlled (acidic and alkaline) conditions of urinary pH. The clinical implication is that possible changes in urinary pH during long-term treatment of arthritic patients may not affect the overall kinetics of indomethacin which is extensively eliminated by the extrarenal route.

Absorption↗

A modified gas-liquid chromatographic assay to monitor plasma mexiletine in a tinnitus study.

In a clinical study of betahistidine, diazepam and mexiletine for the oral chemotherapy of tinnitus, the hospital Pharmacy was requested to devise a double-blind triple cross-over trial including a placebo. As mexiletine is a potent cardiovascular drug and also as a measure of compliance, a rapid and sensitive gas-liquid chromatographic (GLC) method was developed to monitor its plasma concentration in patients who took part in the trial. This assay involved a preliminary ethereal extraction of the drug and internal marker (3-N,N-diethyl carbamyloxy pyridine) in a 1 ml plasma or urine sample under alkaline condition. The concentrated extract was redissolved in distilled methanol (10 microliters) and an aliquot (2 microliters) was analysed by a GLC system (3% OV17 on Gas Chrome Q, 10-100 mesh) linked to a nitrogen sensitive detector. The calibration graphs relating peak height ratios of the drug to the internal marker and concentration were linear and reproducible over the ranges of 5.0 to 100.0 ng/ml and 1.0 to 10.0 micrograms/ml for both plasma and, or urine samples. The steady-state plasma concentrations of mexiletine in 5 patients, from whom blood samples were obtained as a measure of compliance, ranged between 570 to 1911 ng/ml which were similar to those reported from treatment of ventricular arrhythmias with similar dosage regimen of 200 mg mexiletine hydrochloride three times per day.

Adult↗

Disposition of pethidine in man under acidic urinary PH. I. Plasma level and urinary elimination of pethidine and norpethidine.

A detailed study on the plasma and urine levels of pethidine and its major basic metabolite, norpethidine, was carried out after intravenous and oral administration of pethidine, under conditions of controlled acidic urinary pH, to two healthy subjects who had previously shown significant difference in the urinary recovery of pethidine after the intramuscular administration of a standard dose. Utilizing the data of area under plasma concentration-time curve and cumulative urinary excretion of pethidine, similar values of renal clearance of the drug were obtained after separate intravenous and oral administration to the same subject. There is an overall difference in the renal clearance and metabolic pattern of the drug between these two subjects under conditions of controlled acidic urinary pH. It is postulated that variation in the overall elimination of pethidine and other weakly basic drugs can only be elucidated under conditions and may be interpreted in terms of differences in the renal clearance and hepatic biotransformation of the drug.

Administration, Oral↗

The relationship of plasma levels of pyridostigmine to clinical effect in patients with myasthenia gravis.

The relationship between plasma levels of pyridostigmine to clinical evaluation of muscle power was examined in nine patients with myasthenia gravis during treatment with pyridostigmine in doses of 60 to 1040 mg daily. Five of the nine subjects demonstrated a trend towards a positive correlation, but in only two of them was this statistically significant at p < 0.05. In addition, the presence or absence of a possible correlation between muscle power and plasma concentration was not related to the duration of the disease, additional prednisolone therapy or thymectomy.

Adult↗

Properties of alpha-glucosidase from Lactobacillus acidophilus NCTC 1723.

Lactobacillus acidophilus NCTC 1723 produced intracellular and extracellular alpha-glucosidase (alpha-D-glucoside glucohydrolase, EC 3.2.1.20). The alpha-glucosidase was partially purified by ammonium sulphate fractionation and DEAE-cellulose column chromatography, and attained a 10.3-fold purification. The Km for alpha-PNPG was 2.9 mM and the Vmax for alpha-PNPG hydrolysis was 6.45 mumole ml-1 min-1. The enzyme was stable only at pH 6.0-7.5 while incubated at 25 degrees C. At pH 6.5, a 100% activity was retained at 15 degrees-37 degrees C. However, the enzyme was easily destroyed at 50 degrees C. The pH optimum for stability of the enzyme at low temperature (2 degrees C) was between 5 and 6. It was found that addition of Mn++, Ba++ and EDTA, to the medium stimulated alpha-glucosidase activity, while the presence of Hg++, Cu++, Co++, Ni++, Zn++, L-histidine, arabitol, erythritol, sorbitol and glycerol inhibited enzyme activity. Although isomaltase activity was found in the partially purified alpha-glucosidase, it was not known whether this activity was an intrinsic capability of the enzyme. Transglucosylase and weak glucoamylase activities were also found to associate with the partially purified alpha-glucosidase. Since only the alpha-1,6 linked isomaltose was detected as the transferase product, it was thought that the alpha-glucosidase was capable of glucosyl transfer via alpha-1,6-glucosidic bonds.

Glucan 1,4-alpha-Glucosidase↗

Algal single cell protein production from sewage effluent with high salinity.

Laboratory studies indicate that the unicellular green alga Chlorella salina CU-1 could be cultivated in treated sewage effluent with high salinity. The high protein content (51% dry weight), and the relatively complete amino acid profile of the cells, suggest that this alga might be an ideal organism to be used for single cell protein production from high-salinity sewage.

Amino Acids↗