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Biomedical subjects

M Wójcicki

Publications and source records attributed to M Wójcicki.

13 recordsLinked to original sources
PubMed2000

Pharmacokinetics of propranolol and atenolol in patients after partial gastric resection: a comparative study.

OBJECTIVE: Partial gastric resection alters the anatomy and secretory activity of the gastrointestinal tract. It might be expected that the consequences of such changes should affect the pharmacokinetics, especially concerning the absorption of orally administered drugs. Propranolol and atenolol, as representatives of lipophilic and hydrophilic beta-adrenoreceptor antagonists, have been studied in order to define their pharmacokinetic characteristics in patients after partial gastrectomy. METHODS: The study was carried out in 29 patients after gastric resection with Billroth I (B1) anastomosis and in 18 healthy volunteers as controls. Pharmacokinetics of propranolol and atenolol was investigated after a single oral dose of 80 mg and 100 mg, respectively, following a cross-over schedule. Blood samples were collected ten times during the 24 h after the drug administration. Pharmacokinetic parameters of propranolol and atenolol were calculated using a one-compartment open model with first-order absorption. RESULTS: The average blood plasma concentrations of propranolol in gastrectomised patients were lower than those in controls, reaching significance between 1.5 h and 6.0 h of the observation period. Pharmacokinetic parameters of propranolol were different in subjects submitted to surgery compared with healthy persons. We observed a significant decrease in the area under the concentration-time curve (32%) and the peak plasma concentration (20%), and an increase in half-life (25%). Mean plasma concentrations and pharmacokinetic parameters of atenolol in patients following partial gastric resection were not significantly different from those in the controls. No relationship between time interval following partial gastrectomy and pharmacokinetic parameters of the investigated drugs was noted. CONCLUSION: Partial gastrectomy with B1 anastomosis affects the pharmacokinetics of propranolol (lipophilic drug) but not atenolol (hydrophilic drug).

Adrenergic beta-Antagonists↗
PubMed2000

Pharmacokinetics of intravenously administered digoxin and histopathological picture in rabbits with experimental bile duct obstruction.

This study aimed to examine the effect of obstructive cholestasis on the pharmacokinetics of digoxin. Eighteen male rabbits were randomly ascribed to the two study groups: the sham-operated control group and the examined group - with common and cystic bile duct ligations. Digoxin was administered intravenously as a single dose of 0.02 mg/kg, and blood samples were withdrawn for up to 24 h. Digoxin concentrations were determined by the FPIA method. The pharmacokinetic parameters were calculated using a noncompartmental analysis. During the whole observation period the blood serum concentrations of digoxin were statistically higher in animals with obstructive cholestasis versus the controls. A significant increase in the area under the plasma concentration-time curve, decrease in the total body clearance and in the volume of distribution on the 6th day after the bile ducts ligation as compared to the sham-operated controls, were observed. The obtained results suggest an impaired elimination of digoxin in obstructive cholestasis in rabbits.

Animals↗
PubMed1999

CYP2D6 and GSTM1 genotypes in a Polish population.

OBJECTIVE: The aim of the present study was to investigate the distribution of the CYP2D6 and GSTM1 genotypes in a Polish population. METHODS: One hundred and forty-five unrelated healthy individuals from the western region of Poland were studied. The CYP2D6 genotype was analysed by means of polymerase chain reaction (PCR) amplification for the CYP2D6*3 and CYP2D6*4 alleles. The GSTM1 genotype was also analysed by means of a PCR assay to determine two genotypes: GSTM1-1 (positive) and GSTM1-0 (negative). RESULTS: Fourteen subjects (9.6%) were classified as poor metabolisers. The frequency of CYP2D6*4 and CYP2D6*3 was 23.1% and 2.1%, respectively. The frequency of GSTM1 nulled genotype in a Polish population came to 49%. CONCLUSION: The frequencies of poor metabolisers for CYP2D6 and GSTM1 nulled genotype among a Polish population were similar to those observed in other Caucasian populations.

Adolescent↗
PubMed1999

Polymorphism of GSTM1 gene in patients with colorectal cancer and colonic polyps.

The frequency of the GSTM1 gene in patients with nonpolyposis colorectal cancer (CRC) (n = 70) and in subjects with colonic polyps (n = 27) was evaluated and compared with healthy individuals (n = 145). Patients with CRC were divided into the three groups: patients coming from the families with hereditary nonpolyposis colorectal cancer (HNPCC) (n = 17); patients with a high risk of HNPCC who were referred to as suspected of HNPCC (n = 25); patients with sporadic colorectal cancer without clinical features of hereditary tumours (n = 28). A simple polymerase chain reaction (PCR) - based assay to identify GSTM1 nulled and positive (non-nulled) genotype was used. No significant differences in frequency of nulled individuals were observed in both patients with HNPCC and patients suspected of HNPCC as well as in subjects with colonic polyps. The most interesting observation was made in the group of patients with sporadic CRC. Twenty individuals (71.4 %) of the group were GSTM 1 deficient which was significantly different from the control population (p < 0.04). The above data indicate that the absence of the GSTM1 gene is associated with a greater risk of sporadic colorectal cancer. There is an increase in the overall risk of approximately 2.5 as compared with the control population.

Adolescent↗
PubMed1997

Pharmacokinetics of intragastrically administered digoxin in rabbits with experimental bile duct obstruction.

A change in the functioning of the liver as a result of experimental cholestasis could result in a change in the biotransformation of drugs. The aim of this study was to evaluate the effect of extrahepatic cholestasis on the pharmacokinetics of digoxin. The investigation was performed on male rabbits randomly divided into two groups: sham-operated and animals with bile-duct ligation. Digoxin (0.02 mg kg-1) was administered intragastrically as a single dose. Biomedical and anatomo-pathological tests and pharmacokinetic assays were performed before the operation and on the 6th day after surgery. A significant increase in area under the serum concentration-time curve and in mean residence time, a decrease in total body clearance, a reduction in the volume of distribution and increases in maximum concentration and the time to reach maximum concentration were observed in animals with the bile-duct ligation. These results suggest reduced elimination of digoxin in animals with obstructive cholestasis.

Administration, Oral↗
PubMed1996

Pharmacokinetics of phenazone (antipyrine) in rabbits with experimental common bile duct obstruction.

1. An altered functional state of liver due to experimental cholestasis could result in a change in the biotransformation of drugs. The aim of this study was to evaluate an influence of obstructive cholestasis on the pharmacokinetics of phenazone (antipyrine). 2. The investigation was carried out on male rabbits, randomly allocated into two groups: shamoperated and animals with biliary ducts ligation. Phenazone was administered intragastrically as a probe of drug metabolism. 3. Measurements, i.e. laboratory and pharmacodynamic tests, as well as pharmacokinetic assays, were performed before the operation as well as 10-12 days after the bile duct ligation. At the end of the study livers were examined macro- and microscopically and biochemical analysis of the liver microsomes was performed. 4. The measured pharmacokinetic parameters suggested an impaired biotransformation of phenazone in animals with obstructive cholestasis, leading to a slower drug elimination.

Animals↗
PubMed1996

[The effect of experimental extrahepatic cholestasis on absorption, distribution and elimination of digoxin].

Clinical observations indicate an increased number of post-operative complications and deaths in jaundiced patients. The patient may require some simultaneous treatment of concomitant ailments, among which cardiovascular diseases occur rather frequently. Some of the drugs administered then, like digoxin, are, in spite of being predominantly eliminated via the kidneys, metabolized in the liver, secreted into the bile or participating in the enterohepatic circulation. The changed pharmacokinetics of such drugs, in the case of mechanical jaundice, may be due to an altered liver status which can affect the function of the kidneys. The aim of the study was to evaluate the pharmacokinetics of digoxin administered both intravenously and into the stomach, in the state of mechanical, extrahepatic cholestasis. The study was carried out on male rabbits, divided randomly into four groups: the first two (experimental and control) were administered digoxin intragastrically and the next two groups (experimental and control)-intravenously (Tab. 1). The animals of the experimental groups had the bile ducts ligated, whereas the controls were sham-operated on. Digoxin was given to all the animals 4 days before the operation and 6 days after the surgery, in a dose of 0.02 mg/kg. Blood samples were collected ten times for 24 hours after the drug administration. Digoxin concentrations were determined by FPIA method, and pharmacokinetic parameters were calculated by the two compartment open model for intragastric drug administration, and by the noncompartmental analysis for intravenous route. The levels of serum total bilirubin, creatinine, urea, glucose, albumin and activities of alanine, aspartate aminotransferases and alkaline phosphatase were estimated in all of the animals. The rabbits were sacrificed at the end of the study i.e. on the 7th day after the operation. The kidneys and the livers were weighed and examined macro- and microscopically. The laboratory tests as well as the anatomopathological investigations showed the symptoms of cholestasis and the hepatorenal syndrome (Tab. 2, 3). The blood serum concentrations of digoxin, both after intragastric and intravenous administration, were statistically higher during the whole observation period in the animals with obstructive cholestasis versus the controls (Tab. 4, 6). There were no significant alterations of digoxin parameters in the animals of the control groups, measured prior to and after the surgery. In the jaundiced animals, however, most of the pharmacokinetic parameters were markedly changed as compared with the preoperative values. In the rabbits which were given digoxin intragastrically, an increase in area under the plasma concentration-time curve (AUC) and in the peak concentration of the drug (Cmax) was noted (Tab. 5). Besides, the prolongation of mean residence time (MRT) and decrease in total body clearance (Cl) as well as apparent volume of distribution (Vz), were observed, as compared to the sham-operated controls. After the intravenous administration the following changes took place (Tab. 7): an increase in AUC, the prolongation of elimination half-life (t1/2 lambda z) and decrease in the total body clearance. All the above differences were statistically significant. Thus, digoxin, a drug predominantly eliminated via the kidney undergoes an impaired elimination in obstructive cholestasis. Basing on the results of the present study, the following statements could be expressed: (1) experimental, extrahepatic jaundice alters the pharmacokinetics of digoxin given intragastrically as well as intravenously; (2) the administration of therapeutic dose of digoxin in the state of mechanical jaundice may lead to its overdose; (3) obstruction of the common bile duct should indicate the necessity of monitoring the serum concentration of digoxin; (4) extrahepatic cholestasis may induce hepatorenal syndrome.

Absorption↗
PubMedDate not supplied

Pharmacokinetics of lidocaine and its major metabolite- monoethylglycinexylidide (MEGX) in rabbits with experimental common bile duct obstruction.

The aim of this study was to evaluate, using an experimental model, the effect of obstructive cholestasis on the pharmacokinetics of lidocaine and the formation rate of its major metabolite- monoethylglycinexylidide (MEGX)-in rabbits. The investigation was carried out on 20 rabbits, randomly divided into two groups: a control one sham-operated and an experimental one-animals with biliary duct ligation. The measurements, i.e. laboratory and pharmacodynamic tests, as well as pharmacokinetic assays were performed prior to the operation as well as 10-12 days after the bile duct ligation. At the end stage of the study, livers were examined macro- and microscopically and biochemical analysis of the liver microsomes were performed. Lidocaine was given intravenously, as a bolus of 6 mg/kg. Blood for pharmacokinetic assay was sampled within 6 h following the drug administration, and MEGX concentration was evaluated 15 min after lidocaine had been administered. The immunofluorescence polarization method was employed for determination of lidocaine and MEGX concentrations. The one-compartment open model was used for calculations.

Animals↗
PubMedDate not supplied

Antitumor effect of electrochemical therapy on transplantable mouse cancers.

The aim of our study was to assess the antitumor effect of electrochemical therapy (ECT) in the mice bearing advanced transplantable tumours. Mouse mammary cancer 16/C (group 1) and fibrosarcoma F69-3 (group 2) were transplanted subcutaneously (s.c.) into the C3H or BALB/c mice, respectively. Twenty animals in each group bearing measurable s.c. tumours were randomly divided into two subgroups (experimental and control). Two electrodes were inserted into tumours and low level direct current (6-7 V, 5-21 mA) was passed. The animals were observed and tumors were measured twice a week. The animals were sacrificed and autopsied when the tumor diameter reached 2.0 cm. Two animals of each group (experimental and control) were sacrificed for histopathological tumor examination on the 1st and 6th day after ECT. A significant inhibition of tumor growth in mice subjected to ECT was observed, both in those with s.c. growing mammary cancer and with fibrosarcoma. This inhibition was associated with marked prolongation of survival time of ECT-treated mice. It appeared that the mice with mammary cancers were more susceptible to ECT therapy than those with growing s.c. fibrosarcoma. The histopathological studies of tumor specimens from ECT-treated mice showed extensive foci of necrosis with shrinkage of cell nuclei deprived of chromatin. In conclusion, the treatment which inhibits the growth of experimental mammary and fibrosarcoma tumors was demonstrated. However, in no mice complete regression of tumours was observed.

Adenocarcinoma↗
PubMedDate not supplied

Effects of serotonin-active drugs on prolactin secretion in male rats.

The effects of several serotonin acting drugs on serum prolactin levels were studied in male rats. Administration of the serotonin precursor, 5-hydroxytryptophan (5-HTP; 250 mg/kg ip) or pargyline (5 mg/kg ip) with 5-HTP (100 mg/kg ip) significantly increased serum prolactin concentration. Pretreatment of rats with the serotonin agonist, quipazine (10 mg/kg ip) caused increase in serum prolactin levels. Depletion of serotonin stores by pretreatment with p-chloro-phenylalanine methyl-ester (PCPA; 3 x 300 mg/kg ip) significantly prevent the effect of quipazine on prolactin levels. Serotonin uptake blocker, fluoxetine (10 mg/kg ip) produces an increase in the prolactin concentrations of the serum. Administration of the reserpine (2.5 mg/kg sc) did not affect serum prolactin levels. Both serotonin receptor blockers, cyproheptadine (0.5 mg/kg ip) and pizotifen (1 mg/kg ip) caused a week decrease in the serum prolactin levels. Significant changes in concentrations of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in brain of rats pretreated with above serotonin-active drugs were found. These results indicate that serotonergic system can modify secretion of prolactin.

Animals↗