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Biomedical subjects

K Chan

Publications and source records attributed to K Chan.

At least 289 records · Page 16Linked to original sources
PubMed1977

Plasma concentration of pyridostigmine and effects in myastenia gravis.

The relation between the plasma concentration of pyridostigmine and its effects was studied in 5 patients with myasthenia gravis. In 4 patients with typical electromyographic decrement in the adductor pollicis, there was a positive correlation between the concentration of pyridostigmine in plasma and the effect on neuromuscular transmission. The plasma concentration of pyridostigmine required to restore transmission to normal (as calculated from the regression line relating plasma concentration to neuromuscular function) varied over a 5-fold range, reflecting the variable severity of the disease. In another myasthenic patient with purely ocular symptoms, there was a significant correlation between the plasma concentration of the drug and the diameter of the palpebral fissure. It is suggested that the routine measurement of the plasma concentration of pyridostigmine may be of value in the management of myasthenia gravis. A method to calculate the optimal daily dose of pyridostigmine in individual myasthenic patients is described.

Blepharoptosis↗
PubMed1977

Renal clearance of pyridostigmine in patients with myasthenia gravis.

The urinary clearance of pyridostigmine was studied in six patients with myasthenia gravis. In three patients on pyridostigmine alone, renal clearance ranged from 349 to 481 ml/min, corresponding to a pyridostigmine:creatinine clearance ratio of 2.64 to 3.46. In a patient on bendrofluazide as well as pyridostigmine, a similar clearance ratio was observed. By contrast, the urinary clearance of pyridostigmine and the pyridostigmine:creatinine clearance ratio was reduced in two myasthenic patients concurrently treated with other basic drugs. It is suggested that these results may reflect competition for renal tubular excretion.

Adult↗
PubMed1976

A quantitative gas-liquid chromatographic method for the determination of neostigmine and pyridostigmine in human plasma.

A sensitive and selective analytical method was used to measure the concentration of neostigmine and pyridostigmine in human plasma. The procedure involved preliminary ion-pair extraction of the drugs into dichloromethane, followed by concentration and anlysis of the ion-pair complex using a gas-liquid chromatographic system fitted with a nitrogen detector. Using the peak area ratio technique, pyridostigmine bromide was used as the internal standard for the quantitation of neostigmine in plasma; neostigmine bromide was the internal marker for the determination of pyridostigmine. The method depends on the thermal dequaternisation of the quaternary amines, and can be used to detect 5 ng/ml in a 3-ml plasma sample. Accurate measurement can be made at levels of 50-1000 ng/ml. This assay procedure has been applied to the separate determination of the plasma concentration of neostigmine and pyridostigmine after single administration of intravenous doses in aneasthetised patients.

Chromatography, Gas↗
PubMed1975

The effect of ageing on plasma pethidine concentration.

1. Plasma pethidine levels have been monitored after the administration of 1.5 mg/kg intramuscularly to a group of young (under 30) and old (over 70) subjects. 2. Plasma levels were consistently higher in the old group, this was most marked for the first three hours but for most of the study there was a more than two-fold difference. 3. Differences in uptake from muscle and in metabolism were small and appeared unimportant. 4. Less pethidine was excreted in the elderly and this contributed to the overall differences in serum levels but was not important in explaining the marked disparity noted over the first three hours. 5. Red cell binding of pethidine by the young was much greater than by the old and if the differences in drug binding also applies to other tissues this would explain the high serum levels in the old and the increased incidence of side effects.

Adult↗
PubMed1975

Factors influencing the excretion and relative physiological availability of pethidine in man.

Factors influencing the urinary excretion of pethidine, norpethidine and pethidine N-oxide have been examined. The proportion of a dose of pethidine excreted unchanged or as norpethidine depends on the urinary pH and the route of administration. Older people appear to metabolize more of the drug and therefore excrete less unchanged pethidine. The rate of excretion of pethidine in acid urine is directly proportional to the plasma pethidine concentration and under these conditions the relative physiological availability of pethidine has been determined. It has not been possible to explain variations in the amount of pethidine excreted as the N-oxide.

Administration, Oral↗
PubMed1975

A new colonial type of N. gonorrhoeae.

A new variant of Neisseria gonorrhoeae, designated Type 1(1), is described. Colonies of the new type resemble those of Types 1 and 2 in physical characteristics but are granular with a slightly crenated edge and are a deeper gold in colour. The virulence of Type 1(1) in the chick embryo is in keeping with that of Types 1 and 2 but is significantly different from Types 3, 4, and 5. Type 1(1) could be maintained in the laboratory for 6 months, provided that daily selective subcultures were performed. In the absence of this, Type 1(1) reverted to Type 5. It was also possible to preserve the stability of Type 1(1) for long periods by immersion in liquid nitrogen. Pili have been demonstrated on the new type.

Animals↗
PubMed1975

Cultivation of type 1 N. Gonorrhoeae in liquid media.

The effect of CO2 concentration on the growth and colonial stability of Type 1 Neisseria gonorrhoeae has been investigated. Carbon dioxide at a concentration of 16 per cent in air above flasks incubated in a shaker was effective in supporting growth and 100 per cent colonial stability of Types 1, 1', 2, and 4. Lower CO2 tensions increased the generation time of the strains and were less effective in maintaining the stability of virulent variants. Of several liquid media tested, Enriched Single Phase medium, which consists of Difco GC medium base (devoid of agar and starch) to which Lankford supplement and "Isovitalex" have been added, was the most suitable for use with small inocula.

Carbon Dioxide↗
PubMedDate not supplied

Biotransformation of pethidine: a comparative study of 24 h urine in three ethnic groups.

219 surgical patients of either Caucasian, Chinese or Nepalese origin were given pethidine 1 mg/kg by intramuscular injection as pre-operative medication. Urine was collected for 24 h and analysed for pethidine, pethidinic acid, pethidinic acid conjugates, norpethidine, norpethidinic acid, and norpethidinic acid conjugates. The mean proportion of the percentage of metabolites attributable to oxidative demethylation, hydrolysis and conjugation was almost identical in each ethic group (P > 0.2). It was concluded that there were no differences in the metabolic variability of the biotransformation of pethidine in Asians and Caucasians in whom the urine pH had not been acidified.

Adult↗
PubMedDate not supplied

High performance liquid chromatographic characterisation and quantitation of p-aminobenzoic acid N-acetylation in Chinese subjects.

p-Aminobenzoic acid (PABA), p-acetamidobenzoic acid (PADB) and p-aminohippuric acid (PAH) have been separated and determined by a reversed phase, isocratic high performance liquid chromatographic (HPLC) procedure simultaneously. The mobile phase, at 1.5 ml min-1, used was 10 mM sodium hydrogen phosphate buffer, pH 3.5, containing 40% methanol. The eluent was detected at 270 nm. Linear relationship was obtained from 0 to 2.0 micrograms ml-1 of each compound with the corresponding peak-height ratio using p-methylamino-benzoic acid (PMAB) as the internal standard. Urine samples were obtained from healthy Chinese volunteers after oral dosing of 200 mg PABA which was used as a model substance for metabolic investigation of N-acetylation and other conjugation reactions. The 24 hour urinary recovery, from 43 healthy subjects, of PABA, PABA-COOH conjugates, PADB and PADB-COOH conjugates were (mean +/- S.D.) 2.9 +/- 1.5%, 5.2 +/- 3.3%, 13.9 +/- 4.0% and 42.9 +/- 9.8% of the ingested dose respectively. These accounted for 64.9 +/- 12.0% of total dose ingested in 24 hour. In contrast to previously reported findings on one Caucasian subject, no PAH was identified in the urine, and N-acetylation was the major route of metabolism of PABA apart from conjugation at the -COOH group in this group of Chinese volunteers. It is proposed that PABA metabolism may be a useful probe to study ethnic and geographic variation in N-acetylation.

4-Aminobenzoic Acid↗
PubMedDate not supplied

Pharmacokinetics of pyrazinamide in plasma and CSF of rabbits following intravenous and oral administration.

The pharmacokinetics of pyrazinamide (PZA) in cerebrospinal fluid (CSF) and plasma of 10 rabbits were studied after separate intravenous (i.v.) and oral (p.o.) administration, in a cross-over study. Concentrations of PZA in biological fluids were determined by high performance liquid chromatography (HPLC). After p.o. dose PZA was absorbed rapidly and peak plasma concentration was attained at 0.5 h post administration. After i.v. dose, the plasma PZA concentrations declined rapidly within 10 min and subsequently more slowly following a bi-exponential manner. No difference was observed in the area under plasma concentration-time curves indicating oral absorption was complete and no apparent first-pass metabolism occurred. The (mean +/- S.D.) elimination t1/2 after i.v. (1.04 +/- 0.18 h) was significantly shorter (P less than 0.0005) than that after oral (1.95 +/- 0.63 h) dose and the apparent volume of distribution was also significantly smaller (P less than 0.005) after i.v. (3.211 +/- 0.412 l) than after oral (5.936 +/- 1.607 l) administration. The elimination t1/2 of PZA in CSF was nearly identical to that in plasma after either i.v. (1.07 +/- 0.20 h) or p.o. (1.84 +/- 0.56 h) administration. There is no apparent barrier in rabbits for the penetration of PZA into CSF from the general circulation.

Administration, Oral↗
PubMedDate not supplied

Disposition of ethmozine in cerebrospinal fluid and plasma of rabbits.

The concentration-time profiles of ethmozine, a newly introduced anti-arrhythmic drug, in the cerebrospinal fluid (CSF) and plasma of six rabbits (New Zealand white rabbits of both sexes, 4.0-5.0 Kg) were studied after intravenous bolus administration. CSF samples at various intervals were obtained while the animal was lightly anaesthetized with intravenous thiopentone (40 mg Kg-1) and blood samples at other intervals were taken while the animal was conscious. Blood samples (1 ml) were collected from the implanted cannula of the ear artery while CSF samples (0.3 ml) were obtained from the cisterna magna. The plasma concentrations of ethmozine in six rabbits declined rapidly after intravenous injection for up to 30 min. then slowly over 12 h. Using non-compartmental analysis, the mean (+/- S.E.M.) elimination half-life, mean residence time, plasma clearance and volume of distribution at steady state were 13.9 +/- 9.2 h, 19.9 +/- 13.4 h, 2.3 Lh-1 and 26.8 +/- 7.9 L respectively. The mean CSF-plasma concentration ratios for ethmozine at 0.5, 1.0, 2.0, 4.0, 8.0 and 12.0 h were 0.17, 0.14, 0.16, 0.16, 0.23 and 0.22 respectively. The results suggest that ethmozine is able to penetrate into the CSF from the general circulation and this may be related to its adverse effects on the central nervous system.

Animals↗
PubMedDate not supplied

Disposition of epirubicin in an oily contrast medium after intravenous and intrahepato-arterial administration in liver cancer: a preliminary report.

The present study reports findings on the disposition of epirubicin after an intrahepato-arterial administration of the Lipiodol-drug complex, prepared by mixing the drug-aqueous phase with the iodized oil by ultra-sonification, in 14 patients with histologically proven hepatoma or hepatomegaly with serum alpha-fetoprotein level above 500 micrograms.l-1. The volume of Lipiodol used was 5 ml and the epirubicin dose was 50 mg.m-2. Blood samples were obtained at various time intervals up to 72 h post-dose. Serum concentrations of epirubicin were measured by liquid chromatography with fluorometric detection. The area under serum concentration-time curve (AUCinfinity0) was higher in the Lipiodol-epirubicin group (n = 8) while the clearance was faster and elimination t1/2 and mean residence time shorter in the plain epirubicin group (n = 3). However, interindividual variation in metabolism of epirubicin would affect serum level of the drug. In three patients who were given intravenous and intrahepato-arterial injections (90 mg.m-2) of plain epirubicin and Lipiodol-drug complex, the relative bioavailability of Lipiodol-epirubicin complex (F = 0.76 and 0.45) was lower than that of plain epirubicin (F = 0.80 and 0.73) in two patients while it was approximately 100% (F = 1.06 and 1.20) in one patient. It is likely that liver function of the patients might be modified by the disease state over a period of 3 months in the cross-over study. Further studies with larger patient samples are required to confirm if there is a targeting effect of the Lipiodol-drug complex toward hepatoma using a better formulation of the drug in Lipiodol.

Adult↗
PubMedDate not supplied

The effects of Danshen (Salvia miltiorrhiza) on pharmacokinetics and pharmacodynamics of warfarin in rats.

Danshen is a Chinese folk medicine commonly used in the Chinese population. The effects of Danshen on the pharmacokinetics and pharmacodynamics of warfarin were studied in rats. In the pharmacokinetic study, single oral doses of warfarin were administered to rats or after 3 days treatment with Danshen intraperitoneally twice daily. Plasma warfarin concentrations were measured for 48 after each of two warfarin doses by high performance liquid chromatography (HPLC). In the pharmacodynamic study, the treatments were similar to the pharmacokinetic study, the prothrombin time (PT) was measured daily both in the Danshen treatment period and after the warfarin doses for 4 days. The absorption rate (Ka), volume of distribution (Vd) and elimination half-life (T1/2) of warfarin were significantly decreased while Cmax and Tmax were significantly increased after treatment with Danshen. There was no significant change in PT during the Danshen treatment period while the PTs were increased significantly in the first two days after warfarin doses. Our results suggested that Danshen can increase the initial bioavailability of warfarin and also affect the elimination of warfarin. It can also increase the PT further after the warfarin doses. The pharmacokinetic and pharmacodynamic interactions observed in this study indicate a clinically important interaction between Danshen and warfarin if these two agents are taken together.

Animals↗