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Biomedical subjects

H Ehrsson

Publications and source records attributed to H Ehrsson.

At least 55 records · Page 3Linked to original sources
PubMed1986

Degradation of busulfan in aqueous solution.

The influence of pH, phosphate buffer components and temperature on the degradation rate of busulfan was studied. The analysis was performed using gas chromatography with electron capture detection and reversed-phase liquid chromatography with radioactivity monitoring. The degradation rate of busulfan showed no pH dependence in the range pH 1.5-11 and increased at higher pH values. The degradation rate constant was 0.034 +/- 0.001 h(-1) (S.E.M.) for the degradation of busulfan in pure water and 0.45 +/- 0.01 h(-1)M(-1) (S.E.M.) for the reaction of busulfan with the hydroxide ion at 37 degrees C. The reactivity of HPO(4)(-2) was six times higher than the reactivity of H(2)PO(4)(-1) towards busulfan. The hydrolysis products were identified as tetrahydrofuran and methanesulphonic acid by nuclear magnetic resonance spectroscopy.

Journal Article↗
PubMed1985

Drug level monitoring: cytostatics.

The present review on the quantification of cytostatic drugs has mainly been focussed on chromatographic techniques. Special attention has been paid to the precautions that have to be taken into account to ensure the selectivity and accuracy of the various methods. The various cytostatics that have been dealt with are: alkylating agents, antimetabolites, vinca alkaloids, antibiotics, cis-diamminedichloroplatinum, podophyllotoxine derivatives, and nitrosoureas.

Alkylating Agents↗
PubMed1984

Liquid chromatography in anticancer drug research with special reference to anthraquinone glycosides.

The need for individualized cytostatic therapy is most apparent in cancer patients with disturbance of the liver or renal function and also in patients undergoing combination drug therapy. Bioanalytical studies can provide a rationale for increasing the therapeutic index by optimization of the dose schedule and by site-specific anticancer drug therapy. Analytical methods based on liquid chromatography are discussed for the anthraquinone glycosides, where the high selectivity of reversed-phase liquid chromatography systems permits ready separation from their 14-hydroxy metabolites. The high sensitivity of photometric and fluorimetric detectors permits quantification in the low ng/ml range. The stabilization of alkylating agents such as melphalan in biological samples by reaction with acetylcysteine is discussed. The melphalan-acetylcysteine derivative, after isolation from the biological matrix by reversed-phase liquid chromatography, can be detected fluorimetrically with high sensitivity and selectivity.

Journal Article↗
PubMed1984

Binding of busulfan to plasma proteins and blood cells.

The reversible and non-reversible binding of busulfan to plasma proteins and to blood cells has been evaluated in man. The reversible binding to plasma proteins was insignificant in both healthy subjects and in patients with chronic myelocytic leukaemia. The percentage of busulfan irreversibly bound to plasma ligands was 32.4. Busulfan was distributed evenly between blood cells and plasma. The fraction of busulfan irreversibly bound to the blood cells was 46.9%. The major portion of busulfan that is degraded in whole blood reacts with the blood cells and the main part of that binds to macromolecular components in the cells.

Biotransformation↗
PubMed1984

Effect of food on pharmacokinetics of chlorambucil and its main metabolite, phenylacetic acid mustard.

The influence of food intake on the pharmacokinetics of chlorambucil (C) and its cytotoxic metabolite, phenylacetic acid mustard (PAM), has been studied in man after oral doses of chlorambucil. The administration of chlorambucil with food resulted in slower absorption than when fasting. However, the area under the plasma concentration-time curve (AUC) was unaffected. The mean ratio AUCPAM/AUCC was 2.8 (range 1.4-7.1) under fasting and 3.3 (range 1.3-7.4) under nonfasting conditions. The metabolite very probably plays an important role in the cytotoxic effects observed after administration of C, since calculations show that a major fraction of the metabolite is eliminated by alkylation reactions.

Adult↗
PubMed1984

Blood leakage and melphalan leakage from the perfusion circuit during regional hyperthermic perfusion for malignant melanoma.

In regional hyperthermic perfusion with melphalan for patients with malignant melanoma of the leg, plasma leakage between the perfusion circuit and the systemic circulation was 4-7 ml X min-1. The melphalan concentration in the perfusate was biphasic, with half-lives of 8-12 mins for the initial phase and 19-28 mins for the second phase, after the first dose. After a second dose, the corresponding values were 11-13 and 26-34 mins. The highest concentration in general circulation was 0.38 micrograms X ml-1.

Chemotherapy, Cancer, Regional Perfusion↗
PubMed1983

Liquid chromatographic determination of mitomycin C in human plasma and urine.

A method is given for the determination of the antineoplastic drug mitomycin C in plasma and urine samples. Mitomycin is isolated from the biological matrix with the aid of a Sep-Pak C18 extraction column and eluted with methanol. The methanol is evaporated and the residue is redissolved in the chromatographic mobile phase (methanolic phosphate buffer). Mitomycin C is separated from coextracted compounds by reversed-phase liquid chromatography on a LiChrosorb RP-8 column. A high detection sensitivity and selectivity was obtained by photometric measurements at 365 nm. The precision of the determinations was better than 6% relative standard deviation for plasma samples within the range 2-1000 ng/ml, and for urine samples within the range 0.5-4.4 micrograms/ml. The pH-dependent stability of mitomycin in buffer solutions has been studied.

Buffers↗
PubMed1983

Determination of busulfan in plasma by GC-MS with selected-ion monitoring.

A GC-MS technique with selected-ion monitoring is described for the determination of busulfan in plasma. Busulfan is extracted from plasma with methylene chloride and converted to 1,4-diiodobutane. Analysis by GC-MS with selected-ion monitoring (m/z 183) gave a relative standard deviation of +/- 4.3% (n = 5) at the 10-ng/ml level.

Busulfan↗
PubMed1983

Pharmacokinetics of chlorambucil in man after administration of the free drug and its prednisolone ester (prednimustine, Leo 1031).

The pharmacokinetics of chlorambucil has been investigated in a cross over study after oral administration of the free drug (10 mg) and its prednisolone ester (prednimustine, 100 mg). The bioavailability of chlorambucil was about five times lower when given as prednimustine as compared to administration of the free drug. The peak plasma concentration was about twice as high and it was obtained more rapidly when the free drug was given. No intact prednimustine could be detected in plasma.

Aged↗
PubMed1983

Busulfan kinetics.

Busulfan kinetics were studied in patients with chronic myelocytic leukemia after oral doses of 2, 4, and 6 mg. The plasma concentration-time data could be fitted to a zero-order absorption one-compartment open model. The elimination rate constant averaged 0.27 +/- 0.05 hr-1 (SD). The plasma AUC was linearly related to the dose. The lag time for the start of absorption, the time absorption ends, and the absorption rate constant showed some interindividual variations. About 1% of busulfan is excreted unchanged in urine over 24 hr.

Adult↗
PubMed1982

Protein binding of anthraquinone glycosides, with special reference to adriamycin.

The binding of anthraquinone glycosides (adriamycin, adriamycinol, daunorubicin, daunorubicinol, and 4'epiadriamycin) to human serum albumin and human plasma has been studied by equilibrium dialysis. About 62% of adriamycin was bound to human serum albumin (45 g/l). Only minor variations in the degree of binding were observed between the anthraquinone glycosides. The binding degree of adriamycin in plasma from cancer patients was not significantly different from that observed in healthy volunteers, the fraction of free adriamycin being 24.56% +/- 4.51%, and 27.67% +/- 2.78%, respectively. The plasma albumin concentration was significantly lower in cancer patients than in the healthy volunteers (26.90% +/- 5.88% and 39.24% +/- 1.74%, respectively). In cancer patients the fraction of free adriamycin decreased with increasing plasma albumin concentration.

Adsorption↗
PubMed1981

Pharmacokinetics of daunorubicin after administration as free drug or as DNA complex in leukemic patients.

An earlier whole-body autoradiographic study in mice revealed large differences between the tissue distribution of daunorubicin (D) after administration as free drug as as DNA-linked D. Therefore, the pharmacokinetics of D administered as free drug or linked to DNA was studied in 15 adult patients with acute non-lymphoblastic leukemia. The data obtained following infusion of free drug over either 45 or 240 min could be fitted to a two-compartment open-body model. With the D-DNA infusion considerably higher plasma concentrations were achieved, with a slower distribution and elimination from plasma than seen after the administration of free drug. this confirmed earlier animal data indicating a different pharmacokinetic behavior of D when it was administered linked to DNA. Furthermore, different pharmacokinetic parameters were obtained for D during infusion and in the post-infusion phase after administration of DNA-linked D (P less than 0.005). This finding strongly indicates that the D-DNA acts as a slow-release preparation in humans, which might modify tissue distribution and toxic side-effects of the drug.

DNA↗
PubMed1980

Determination of chlorambucil in plasma by GLC with selected-ion monitoring.

A GLC technique with selected-ion monitoring is described for chlorambucil determination in plasma using [2H]chlorambucil as the internal standard. Chlorambucil is extracted from plasma with methylene chloride at pH 3 and converted to a thiazane derivative by reaction with 0.1 M sodium sulfide at 80 degrees. The carboxylic group of the chlorambucil derivative is derivatized with allyl bromide using extractive alkylation. Analysis by selected-ion monitoring was performed by focusing at m/e 305 (M) and 313. The relative standard deviation was +/- 5% (n = 5) at the 10-ng/ml level.

Alkylation↗