Search PubMed⌕ Search

Biomedical subjects

K Chan

Publications and source records attributed to K Chan.

At least 235 records · Page 13Linked to original sources

Compliance with oral drug therapy in patients with hematologic malignancy.

Compliance with oral self-administered allopurinol (daily medication) and prednisone (intermittent medication) as well as compliance with monthly scheduled clinic appointments, were examined in 108 patients with newly diagnosed hematologic malignancy. Baseline levels of compliance (control group) were compared to results obtained after implementation of three intervention packages, whose aim was to increase compliance. The packages included combinations of education, home psychologic support and restructuring, and training in pill taking. A 24-hour profile of the two drugs and their metabolites was first determined. Serum samples were then obtained monthly over 6 months and analyzed for presence of the drugs. Control patients were fully compliant with allopurinol only 16.8% of the time. This rate increased significantly (44% to 48% of the time) for those who received any one of the intervention programs. With respect to prednisone, control patients were compliant 26.8% of the time, with no real improvement after interventions. Finally, self reports overestimated compliance by a factor of two when compared to drug analysis. The results indicated that full compliance with oral medications was remarkably low among our patients who have treatable and in some cases curable hematologic malignancy. However, compliance can be significantly improved by the use of various intervention packages.

Administration, Oral↗

A study of prescribed H1-antihistamine preparations over a period of 12 months in community pharmacy.

A survey on the prescribing pattern of H1-antihistamine preparations was carried out in four socio-economic areas in Liverpool: the City Centre, an Affluent Area, a Poor area and a Council Estate. The purpose of this study was to find out which H1-antihistamines were prescribed from the wide range available; to discover if there was a trend in the use of these agents over a 12-month period and to suggest possible explanations for these findings. The majority of H1-antihistamine preparations were prescribed in the Affluent Area followed by the City Centre, Poor Area and the Council Estate. In all four areas, over 7.0% of all total items dispensed in a year contained H1-antihistamine drugs, and the lowest use (3.7-9.2%) fell in the summer months while the highest use was in January (8.2-14.1% of items containing H1-antihistamine dispensed per month). Thus the general trend in the use of these drugs may not follow the trend of the hay fever season and it is probably true that H1-antihistamines were more frequently prescribed for treatment of other conditions (common cough and cold) than rhinitis alone. The most widely prescribed classes of H1-antihistamines were alkylamines and ethanolamines, followed by the phenothiazines and ethylenediamines while the piperazines were not prescribed. Triprolidine, diphenhydramine, promethazine and brompheniramine were the top four most widely prescribed drugs.

Dosage Forms↗

Influence of urinary pH on pethidine kinetics in healthy volunteer subjects. 2. A study of ten Chinese subjects.

The pharmacokinetics of intravenous pethidine (150 micrograms kg-1) were determined in 10 healthy Chinese subjects under controlled (acidic and alkaline) and uncontrolled urinary pH. Large variations in the 48 hr urinary recoveries of pethidine and norpethidine were induced by change in urinary pH: (mean +/- S.D.): 24.3 +/- 7.3% & 33.0 +/- 11.4%, 0.4 +/- 0.3% & 3.8 +/- 2.2%, 11.4 +/- 6.9% & 13.9 +/- 2.5%, respectively, under acidic, alkaline and uncontrolled urinary pH for pethidine and norpethidine. There was no significant difference in the terminal half-lives, t 1/2 (6.1 to 7.0 hr) of pethidine, although the area under the plasma concentration-time curve under acidic urinary conditions was slightly lower and renal clearance of the drug higher than those under alkaline and uncontrolled urinary conditions. Confirming previous results from Caucasian subjects, under all 3 conditions pethidine disappeared from the plasma tri-exponentially and acidification of the urine may increase body clearance of unchanged pethidine due mainly to greater renal clearance of the drug; this may be useful clinically to treat acute pethidine poisoning. However, under acidic urinary conditions, Chinese subjects excreted more norpethidine than Caucasians (33.0 +/- 11.4% and 23.4 +/- 4.6%, respectively).

Adult↗

Disposition of pethidine in man under acidic urinary pH. 3. A comparison of pharmacokinetics among Caucasian, Chinese and Indian subjects.

The pharmacokinetics of low dose pethidine (150 micrograms kg-1) after intravenous administration were determined in 10 Caucasian, 10 Chinese and 10 Indian healthy volunteers under conditions of acidic urinary pH. Plasma and urine concentrations of pethidine and norpethidine were measured by gas liquid chromatography. In all 3 ethnic groups, the disappearance of pethidine from plasma was best described by a tri-exponential function. No significant differences were observed in the elimination half life, renal clearance and total plasma clearance of the drug. The significantly lower AUC and higher (approaching significance) apparent volume of distribution in the 2 Asian groups may be explained in terms of more readily distribution of the drug (significantly higher K21 rate constants were obtained from both Chinese and Indian subjects according to a 3-compartment open model) due possibly to more frequent movement of these subjects during the early part of experiment. More norpethidine was recovered in the urine of the Chinese and Indian subjects; this may suggest an interethnic difference in the oxidative demethylation of pethidine.

Adult↗

High-performance liquid chromatographic determination of pyrazinamide in cerebrospinal fluid and plasma in the rabbit.

A simple procedure for the determination of pyrazinamide in plasma and cerebrospinal fluid in the rabbit is described. The assay involves a preliminary extraction of the drug and an internal standard, paracetamol, from the acidified sample (pH 4.2). The extract is evaporated to dryness at 45 degrees C and the residue is redissolved in methanol (50 microliters). A 25-microliters aliquot is injected into the liquid chromatograph and eluted with acetonitrile-10 mM phosphate buffer of pH 3.5 (10:90, v/v) on a 30-microns C8 pre-column linked to a 5-microns C8 reversed-phase column at ambient temperature (25 +/- 1 degree C). The eluate is detected at 215 nm. The method has been used to investigate the disposition of pyrazinamide in plasma and cerebrospinal fluid in six rabbits.

Animals↗

Rapid high performance liquid chromatographic assay of cephalosporins in biological fluids.

A simple isocratic HPLC method is described for the rapid analysis of cephalosporins in body fluids. Sample preparation by protein precipitation takes only five minutes; HPLC analysis is completed within two to ten minutes, using one of two simple solvent mixtures eluted on a single C18 reversed phase column. Nine cephalosporins and nine types of body fluid were formally analysed, but the system was also found to be suitable for the assay of benzyl penicillin, ampicillin, cloxacillin, carbenicillin and chloramphenicol. It is likely that this method, with only minor modifications, would be suitable for the analysis of most beta-lactam antibiotics in most clinical specimens. The method is therefore particularly recommended for use in clinical laboratories.

Body Fluids↗

Rifampicin concentrations in cerebrospinal fluid and plasma of the rabbit by high performance liquid chromatography.

A high performance liquid chromatographic (HPLC) assay has been developed for the measurement of rifampicin in cerebrospinal fluid and plasma samples in the rabbit. The method involved a preliminary organic solvent extraction of the drug and p-dimethylaminobenzoic acid (internal standard) from biological samples and subsequent concentration and analysis by HPLC. An aliquot (25 microliters) of the concentrate was injected into the liquid chromatograph and eluted with acetonitrile-10 mM phosphate buffer of pH 3.5 (48: 52, v/v) on a 30 microns C8 reversed phase column linked to a 5 microns C8 analytical column at ambient temperature (25 +/- 1 degrees C). The eluate was detected at 215 nm. The method has been used to investigate the disposition of rifampicin in plasma and CSF in rabbits.

Administration, Oral↗

Simultaneous determination of carbamazepine and its epoxide metabolite in plasma and urine by high-performance liquid chromatography.

A simple procedure for the simultaneous determination of carbamazepine and its major metabolite, carbamazepine epoxide, in plasma and urine is described. The assay involves two extractions of the drugs and an internal marker, clonazepam, from the alkalinized sample. The extract is evaporated to dryness at 45 degrees C and the residue is redissolved in methanol (30 microliters). A 25-microliters aliquot is injected into the liquid chromatograph and eluted with acetonitrile-water (40:60, v/v) on a C18 pre-column linked to a 5-microns C8 reversed-phase column. The eluent is detected at 215 nm. The method has been used to investigate the steady-state concentrations of carbamazepine and carbamazepine epoxide in the plasma and urine of a manic-depressive patient.

Bipolar Disorder↗

Pharmacokinetic contributions to drug use.

Fundamental research in pharmacokinetics help to identify the causes of inter-subject variability in response to drugs. An understanding of these causes may permit the development of an individual dosage schedule and improve drug therapy. All professionals who are involved with drug use in patients should have a good knowledge of drug disposition and clinical pharmacokinetics.

Aging↗

Pharmacokinetics of low-dose 1-beta-D-arabinofuranosylcytosine given by continuous intravenous infusion over twenty-one days.

The pharmacokinetic parameters of low dose 1-beta-D-arabinofuranosylcytosine (ara-C) infusions were studied in 11 patients, 6 males and 5 females, with a mean age of 68.5 +/- 13.8 (SD) years. The drug was infused to 4 patients with pre-leukemia (refractory anemia with excess blasts), 5 patients with acute myelogenous leukemia, and 2 patients with secondary leukemia due to chemotherapy, at a dosage of 20 mg/m2/day over 21 days. The patients' blood and urine were analyzed for ara-C content by radioimmunoassay. Mean steady state plasma levels of 7.7 +/- 4.7 ng/ml (31.7 +/- 19.3 nM) (n = 189) and a range 0.6 (2.5 nM) (lower limit of assay) to 29.7 ng/ml (122.1 nM), with significant inter- and intra-patient variations, were reached within about 2.7 h. The plasma levels of ara-C decreased rapidly, with a t1/2 alpha of about 12 min following discontinuation of the infusion, followed by a very slow t 1/2 beta of about 19 h. Other parameters (mean values of 10 or 11 patients) were: area under the curve, 182.1 +/- 64.8 ng X day/ml; total body clearance, 188.7 +/- 54.8 liters/h; renal clearance, 3.1 +/- 1.4 liters/h; volume of distribution at steady state, 53,913 +/- 17,626 liters; and recovery of ara-C in urine, 1.43 +/- 0.69% (n = 226) of daily administered ara-C. A linear relationship was observed with administered dose when the mean plasma levels of our study were compared with the ones reported for conventional ara-C infusions. Plasma clearance was comparable to that observed in conventional dose, when the observed values were extrapolated to the dose administered in this study.

Aged↗

An improved gas liquid chromatographic assay for plasma valproic acid concentrations in mentally handicapped epileptic children.

A gas liquid chromatographic (GLC) method is described for the determination of valproic acid concentrations in plasma. This simple, rapid and reproducible assay involved chloroform (500 microliter) extraction of the drug and internal standard (octanoic acid) from acidified plasma samples. An aliquot (1 microliter) of the unconcentrated organic extract was injected directly into the GLC system (a coiled glass column 1 m long, 6 mm OD packed with 5% diethylene-glycol-succinate-phosphate on 100/120 mesh Supelcoport) with detection by flame-ionization. This assay was successfully employed to measure plasma concentrations of valproic acid in 42 mentally handicapped, epileptic children of Chinese origin, most of whom were on multiple anti-epileptic agents.

Child↗

Influence of urinary pH on pethidine kinetics in healthy volunteer subjects.

The kinetics of intravenous pethidine (150 micrograms kg-1) were determined in 10 healthy Caucasian subjects under uncontrolled and controlled (acidic and alkaline) urinary pH. Although large variations in the 48 hr urinary recovery of pethidine and norpethidine (26.9 +/- 5.9% & 23.4 +/- 4.6%, 0.6 +/- 0.3% & 3.6 +/- 1.6%, 6.9 +/- 3.2% & 17.4 +/- 6.6%, respectively, under acidic, alkaline and uncontrolled urinary pH were induced by change in urinary pH, the terminal t1/2 (7-8 hr), the AUC and the plasma concentration-time profiles were not affected. Under all these conditions, the disappearance of pethidine from the plasma was described by a triexponential function. A 3-compartment open model with input into the central compartment and elimination from both the central and the fast accessible (metabolising) compartment was proposed to interpret pethidine distribution in the body. This model explains the complimentary elimination of pethidine by renal excretion and metabolism. Under alkaline urinary pH, the hydrolytic route predominates as recovery of pethidine and norpethidine in the urine is significantly lower under this condition. Acidification of the urine may increase body clearance of the unchanged drug due mainly to greater renal clearance, and this may be useful clinically to treat acute pethidine poisoning and when the complimentary hepatic metabolism is impaired.

Adult↗

Quantitative capillary column gas chromatographic method for the determination of glycopyrronium in human plasma.

A new sensitive and selective capillary column gas chromatographic method for the anti-cholinergic agent glycopyrronium bromide in human plasma is described. The procedure involves preliminary ion-pair extraction of the drug into dichloromethane, followed by concentration and analysis of the ion-pair complex by capillary column gas chromatography using a nitrogen-sensitive detector. The method depends on the thermal dequaternisation of the quaternary ammonium compound and can be used to detect 5 ng/ml in a 3-ml plasma sample. The assay procedure has been applied to the determination of the plasma concentration of glycopyrronium after intravenous administration to an anaesthetised patient.

Benzilates↗

Elimination of phenoperidine in liver disease.

The disposition and elimination of phenoperidine was studied in five normal subjects, and in six patients with hepatic disease. Plasma concentrations of phenoperidine were generally higher in patients with hepatic dysfunction. Secondary peaks were observed between 15 and 105 min (particularly in patients with liver disease). In the patients the terminal half-life of phenoperidine was prolonged by approximately 50%, mainly because of a decrease in the clearance of the drug. There was little or no change in the total apparent volume of distribution. However, the differences between normal subjects and patients with hepatic disease were not statistically significant. The results suggest that slight or moderate impairment of hepatic function does not significantly affect the kinetics of the drug, and that modification of its dosage may not be required.

Adult↗

The simultaneous determination of five anti-epileptic drugs in plasma by high performance liquid chromatography.

A high performance liquid chromatographic (HPLC) method is described for the simultaneous determination in plasma of carbamazepine, ethosuximide, phenobarbitone, phenytoin and primidone. The procedure involved the preliminary extraction of the drugs and the internal standard (hexobarbitone) into a mixture of organic solvents at pH 2. The dried extract was dissolved in methanol and 25 microliter of the concentrate was injected into a liquid chromatograph linked to a reverse-phase column. The drugs and internal standard were eluted from the column by a mixture of methanol and water, as the mobile phase, and detected with a UV spectrophotometer at 204 nm. This HPLC assay, which required 0.5 ml of plasma, was used to determine anti-epileptic drugs levels in 136 mentally-handicapped children suffering from epilepsy. Comparison between different batches of assays showed that recovery of the drugs from plasma varied from 60 to 98% and with a coefficient of variance between 3.8 to 9.8%. Detection limit of the method ranged from 2 micrograms ml-1 for primidone, to 1 microgram ml-1 for the remainder of the anti-epileptic drugs.

Anticonvulsants↗