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Biomedical subjects

K K Chan

Publications and source records attributed to K K Chan.

At least 217 records · Page 12Linked to original sources
PubMed1978

High-presssure liquid chromatographic determination of methotrexate and its major metabolite, 7-hydroxymethotrexate, in human plasma.

A rapid high-pressure liquid chromatographic assay is described for the analysis of methotrexate (MTX) and its major metabolite, 7-hydroxymethotrexate (7-OH-MTX), in plasma samples from patients following high-dose therapy. The method involves an ion-pair extraction of MTX from plasma with chromatography on a microparticulate anion-exchange column using ultraviolet detection at either 254 or 315 nm. Maximum sensitivity achieved was 1 X 10(-7) M. In addition to being specific for parent MTX, this procedure was used to detect and quantitate significant concentrations of 7-OH-MTX in several patients. Comparison to a protein-binding method indicated a greater degree of specificity for the chromatographic procedure. The procedure can be used to allow therapeutic monitoring of plasma MTX and metabolite for patients receiving high-dose MTX therapy as well as to determine the purity of formulations of MTX used clinically. In addition, the procedure is applicable to the support of pharmacokinetic studies of MTX in animals and man.

Animals↗
PubMed1978

Prediction of adriamycin disposition in cancer patients using a physiologic, pharmacokinetic model.

A ten-compartment flow-limited pharmacokinetic model scaled from rabbit tissue distribution data was used to predict plasma adriamycin concentrations in 23 patients and adriamycin tissue uptake in nine surgery patients following iv bolus doses of 10--60 mg/m2. The predicted concentrations were compared to experimentally determined adriamycin using a specific thin-layer chromatographic fluorescence scanning procedure. The predicted plasma time course for 11 of 16 patients with relatively normal liver and kidney function agreed closely with the observed plasma time course. Deviations in the other five patients were ascribed to possible changes in the profile of metabolite formation and/or fluctuations in biliary clearance. All four patients with elevated serum bilirubin demonstrated significantly higher and more prolonged plasma levels than predicted. The results of two patients with impaired kidney function and one patient with both hepatic and renal involvement were inconclusive. The comparison between predicted and observed tissue concentrations in biopsy samples was varied; however, all were within an order of magnitude. It is concluded that the model depicts adriamycin uptake and distribution reasonably well; however, more needs to be known concerning individual variation in metabolic and biliary excretion rates for this to become more patient-specific. Also, a tumor compartment appears to be an important addition in modifying the model to allow for clinical utility.

Animals↗
PubMed1977

Immediate post-placental insertion of intrauterine contraceptive devices.

Insertion of one of three types of intrauterine contraceptive device--the Lem, copper 7, and 'Progestasert' system--was carried out in 274 obstetric patients. These devices were all inserted within 20 min of delivery of the placenta and membranes, with a special 25 cm inserter. The expulsion-rate was low (less than 7%), and there were no uterine perforations. There was no difference in puerperal morbidity between these patients and a matched control group, and no cases of pelvic sepsis developed.

Contraception↗
PubMed1977

Synthesis of 5-azacytidine-6-13C and -6-14C.

5-Azacytidine (1) labeled with 13C or 14C at the chemically labile C-6 position was synthesized. A method utilizing hydrolytic opening of the triazine ring followed by recyclization with dimethylformamide dimethyl acetal was used. Urinary and biliary excretion was measured in rabbits following intravenous doses of 1-4-14C and 1-6-14C. Differences in recoveries of the dose from 4-14C and 6-14C demonstrate that ring cleavage of 1 with loss of the C-6 carbon represents a major metabolite route.

Animals↗
PubMed1976

Rapid analytic method for adriamycin and metabolites in human plasma by a thin-film fluorescence scanner.

A rapid and highly sensitive method is described for the quantitative determination of adriamycin and metabolites in plasma. Adriamycin (Ad) with daunorubicin added as the internal standard was extracted from plasma with chloroform-isopropanol (1:1), separated by thin-layer chromatography (TLC), and quantitated in situ via a fluorescence scanning technique. This method represents one of the very few reliable quantitative TLC methods and is suitable for the routine determination of Ad in plasma in amounts as low as 2 ng/ml. Plasma Ad levels at 24 hours in rabbits and in patients both given a 1-mg/kg dose, previously regarded as difficult to be measured, are now easily measurable using as little as 0.5 ml of plasma. Multiple samples (ten to 15) can be analyzed by this method within a day.

Animals↗
PubMed1974

Warfarin. Stereochemical aspects of its metabolism and the interaction with phenylbutazone.

An examination of the metabolic fate of the R and the S isomers of warfarin revealed that the two isomers were metabolized by different routes. R warfarin was oxidized to 6-hydroxywarfarin and was reduced to the (R,S) warfarin alcohol. In contrast, S warfarin was oxidized to 7-hydroxywarfarin and was reduced to the (S,S) warfarin alcohol. S warfarin was also oxidized to 6-hydroxywarfarin. These observations suggested that interactions between warfarin and other drugs might be manifest stereo-specifically, i.e., have a different effect on the isomers of warfarin, so a series of experiments were conducted with each isomer of warfarin, before and after phenylbutazone. The plasma clearance of S warfarin was slowed from 3.1 to 1.1% per h in one subject and from 2.3 to 1.6% per h in another. In contrast, the clearance of R warfarin was increased from 1.5 to 3.0% per h and from 0.9 to 1.6% per h in two subjects after phenylbutazone. The rate of clearance of racemic warfarin was unaffected by phenylbutazone; the depression of the rate of clearance of the S isomer masked the stimulation of the clearance of the R isomer. Since S warfarin is five times more potent an anticoagulant than R warfarin, it is concluded that inhibition of the metabolism of S warfarin provides one mechanism for the augmented anticoagulation which follows phenylbutazone.

Blood Coagulation↗
PubMedDate not supplied

Microcomputer based pharmacokinetic programs for calculating absorption rate.

A package of microcomputer based pharmacokinetic programs for evaluating in vivo absorption rate has been developed. The following programs are included in the package: TEXT FILE (program to create a data file which can be accessed by all pharmacokinetic programs), WN12GT (Wagner-Nelson method), LOO (modified Loo-Riegelman method), DECON (deconvolution method), and MODMOMT (method of statistical moments). All programs were tested with data obtained from standard texts or original articles. This package of programs designed to be interactive, flexible, and easily used by a novice. The modular design facilitates modification, upkeep and accommodation of new methods of calculation.

Absorption↗