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Biomedical subjects

I Bartosek

Publications and source records attributed to I Bartosek.

At least 55 records · Page 3Linked to original sources
PubMed1976

6-Aminochrysene kinetics in isolated perfused liver.

1. New quantitative assays of 6-aminochrysene by spectrophotometric and g.l.c. methods and t.l.c. separation systems are described. 2. The decline in blood levels of the antitumoral agent 6-aminochrysene was due to its distribution rather than to metabolism to polar metabolites, during liver perfusion experiments. 3. No marked changes in kinetics of 6-aminochrysene were observed during perfusion of livers isolated both from normal and from Walker 256 carcinosarcoma-bearing rats.

Animals↗
PubMed1976

Effect of phenobarbital on cyclophosphamide metabolism in rats.

1. The pharmacokinetics of cyclophosphamide and its alkylating metabolites have been studied in rats whose liver microsomal enzymes had been induced by phenobarbital pre-treatment. 2. Serum levels of cyclophosphamide were determined using a new g.l.c. method. The half-life of cyclophosphamide in blood of rats pre-treated with phenobarbital was shorter than in control rats. This change is closely related to higher rates of production of p-nitrobenzylpyridine-positive alkylating metabolites of cyclophosphamide, which in turn is followed by their more rapid disappearance from the circulation. 3. Urinary excretion reflects this situation; lower amounts of cyclophosphamide and higher concentrations of its alkylating metabolites are present in the urine of phenobarbital-treated rats. 4. Perfusion of livers isolated from phenobarbital-pre-treated rats confirmed the results in vivo. With this preparation, too, disappearance of cyclophosphamide was more rapid and formation of its alkylating metabolites was accelerated after phenobarbital treatment.

Alkylating Agents↗
PubMed1976

Importance of pharmacokinetic studies on cyclophosphamide (NSC-26271) in understanding its cytotoxic effect.

Pharmacokinetic studies on cyclophosphamide (CP) and its alkylating metabolites produced by hepatic biotransformation have been performed in vivo in animals and in vitro in the perfused liver. CP levels were determined by a gas-chromatographic method combined with mass-spectrometry, and production of alkylating metabolites was assayed by the 4-(4-nitrobenzyl)pyridine reaction for alkylating compounds. Differenes in serum drug levels between normal rats and rats bearing Walker 256 carcinosarcoma were observed in vivo and were confirmed by the liver-perfusion technique. Pharmacokinetic parameters and enzyme kinetic data both in normal and in tumor-bearing animals will be presented. The disappearance of CP and the corresponding formation of CP metabolites was significantly modified when (a) CP was given after previous treatment with a compound which alters its biotransformation (ie, phenobarbital, an inducer of microsomal metabolism), (b) CP was given after previous treatment with CP (which inhibits microsomal metablism), or (c) CP was given with competitive substrates of aldehyde oxidase or dehydrogenase (glyceraldehyde, chloral hydrate, and disulfiram). Results obtained in animals or in the perfused liver will be discussed. The significance of this modified CP metabolism in influencing its cytotoxic effect will be discussed and correlations between drug levels and activity will be presented.

Animals↗
PubMedDate not supplied

Effect of fasting, induction, sex and age on clearance of benz(a)anthracene and chrysene by isolated perfused rat liver.

Hepatic clearances of benz(a)anthracene (B(a)A) and chrysene (Ch) by isolated perfused liver of female rats were similar when measured with hydrocarbons singly (B(a)A 4.3 ml/min, Ch 5.1 ml/min) or in a mixture (4.7 resp. 5.3 ml/min). Clearance of both isomers by livers from 24 h fasted donors was approximately halved. In vivo pretreatment with B(a)A (22.8 mg per kg for 2 days) significantly increased elimination of both hydrocarbons. Hepatic clearance of B(a)A was significantly higher in male rats than in females of the same age (8 weeks). Elimination of both hydrocarbons was significantly lower in 2 year-old males.

Aging↗
PubMedDate not supplied

Pharmacokinetics of amiodarone in rats.

We studied the kinetics of amiodarone in the rat. After an intravenous dose of 50 mg/kg, the time-course of the drug concentrations was assessed by high-pressure liquid chromatography in blood and tissues up to 16 h. The drug disappeared from the blood with an elimination half-life (t1/2beta) of 514 min and distributed extensively into tissues [apparent volume of distribution (Vd)= 29.51 L/kg]. Concentrations were highest in liver, kidney, and heart, and lowest at all times in the brain. The highest concentrations were found within 5-30 min of administration. Amiodarone accumulated extensively in adipose tissue and reached a fat/blood concentration ratio of about 1,000 at 16 h. Single-pass rat liver perfusion experiments gave an hepatic extraction ratio of 0.49 and an intrinsic clearance of 5.48 ml/min. Amiodarone disappearance in rat liver recirculation experiments was biexponential, with a half-life of 58 min.

Amiodarone↗
PubMedDate not supplied

Antitumor activity of the novel nitrosourea S10036 in rodent tumors.

The activity of the novel anticancer agent diethyl 1-3-(chloroethyl)-3-nitrosoureido ethyl phosphonate (S10036) was investigated on several rodent tumors. S10036 showed a good efficacy, comparable to that of the anticancer agent BCNU, against i.p transplanted P388 and L1210 leukemias. S10036 was very effective against the primary tumor and metastases of i.m transplanted M5076 reticular cell sarcoma of the mouse and against subline A of the Walker carcinoma of the rat. It was inactive against rodent tumors resistant to BCNU such as L1210/BCNU, ICIG-Ci4 murine fibrosarcoma and the Walker carcinoma subline B in the rat.

Animals↗