PubMed Health⌕ Search

Biomedical subjects

M J Czejka

Publications and source records attributed to M J Czejka.

At least 19 recordsLinked to original sources
PubMed1992

Red blood cell partitioning of gallopamil, verapamil and norverapamil.

In-vitro binding of calcium-antagonists gallopamil and verapamil (and its main metabolite norverapamil) to human red blood cells (RBCs) was investigated. The drugs are bound reversibly and dose dependent to RBCs in the same order of magnitude, with partition-coefficients of kRBC = 0.12-0.34 for gallopamil, kRBC = 0.10-0.30 for verapamil and kRBC = 0.10-0.27 for norverapamil. The data indicate that, although RBCs may act as subcompartments of the blood for this class of compounds, they may have no influence on therapeutic plasma concentrations, due to their low kRBC.

Biological Availability↗
PubMed1992

Influence of interferon alfa-2b with or without folinic acid on pharmacokinetics of fluorouracil.

Interferon alfa has been demonstrated to enhance the effect of fluorouracil (5-FU) on human colon cancer cell lines as well as in clinical studies. By several authors interest in focussed on the question whether the interaction between these two agents is reflected by changes of 5-FU kinetics. In the present study the pharmacokinetic behavior of 5-FU was investigated in combination with interferon alfa (IFN-alpha-2b) and further after adding the second well-established biomodulating agent folinic acid (FA). Ten patients with advanced gastrointestinal cancer received 5-FU as a weekly bolus injection of 750 mg/m2, IFN-alpha-2b 5 million units three times per week subcutaneously and FA as a short time infusion at 200 mg/m2. 5-FU plasma levels were determined by high performance liquid chromatography as a baseline measurement on day 1 before starting IFN-alpha-2b. Analysis was repeated at the second or third cycle of 5-FU administration 1 hour after the last IFN-alpha-2b injection, and finally after also adding FA immediately infused before 5-FU injection. Biomodulation of 5-FU by IFN-alpha-2b alone resulted in a significant alteration of 5-FU kinetic parameters as demonstrated by an increase of area under the curve by 80%, and of blood concentration (co) by 65%, and a decrease of total clearance at 50%. These data may partly explain the observed enhancement of antiproliferative and toxic effects of this combination. On the other hand, when FA was added to this schedule, no significant changes of 5-FU kinetics could be documented. Therefore the theoretical benefit of such a double modulation cannot be supported by our findings. Further preclinical and clinical investigations are required to define the role of a triple combination of 5-FU with IFN-alpha-2b and FA.

Aged↗
PubMed1992

Pharmacokinetic aspects of interferon alfa-2b after intrahepatic or intraperitoneal administration.

The pharmacokinetics of interferon alfa-2b (IFN-alpha-2b) were determined following intraperitoneal (IP) infusion of escalating doses, ie, 5, 10, and 15 million units (MU) and intrahepatal-intraarterial (IA) (IA, bolus v 24 hours continuous infusion of 3 and 5 MU) administration in patients with metastatic cancer. Pharmacokinetic parameters show that bioavailability of IFN-alpha-2b after IP administration is 30 times higher for the peritoneal fluid (PF) than for peripheral blood (PB) explaining also the low incidence of side effects. The high affinity of IFN-alpha-2b to the peritoneal cavity is furthermore substantiated by the total compartment clearance, which is only about 1 1/minute for the PF in comparison to about 30 1/minute as determined for PB. IFN-alpha-2b is eliminated from the PF with a half life (t1/2) of elimination 10 to 32 hours and from the blood with t1/2 of 5 to 13 hours. After IA bolus, IFN is distributed from the blood with a t1/2 below, 2 hours, with dose-dependent serum peak concentrations (c = 47 IU for 3 MU and 145 IU for 5 MU). Twenty-four-hour infusion leads to a steady state within 4 to 6 hours and maximum concentration of 8.5 or 12.5 IU/mL, respectively. During infusion IFN alpha-2b is slowly eliminated with a t1/2 of 16 hours. The lower area under the curve levels after bolus injection may suggest a better tissue uptake of IFN-alpha-2b by the liver. Further studies on pharmacokinetics are warranted to establish exact dose recommendations for an optimal schedule using this route and mode of IFN-alpha-2b administration in mono- and combination therapies.

Female↗
PubMed1991

[Pharmacokinetic aspects of the combination of interferon-alpha-2b and folic acid with fluorouracil].

The plasma levels of fluorouracil (5-fluorouracil, 5FU; CAS 51-21-8) after intravenous administration have been monitored without, under influence of interferon-alpha-2b (IFN) and under influence of IFN combined with folic acid (FA). IFN causes a highly significant change of the pharmacokinetic parameters of 5FU (p less than 0.001) compared to 5FU administration without IFN. The bioavailability of 5FU (compared as the AUC0-60 values) is elevated to 80%. In contrary, the combination of IFN with FA leads to a non-significant change of the 5FU pharmacokinetics, although the bioavailability is increased to 18%. The higher plasma levels of 5FU under the influence of IFN might be causes by a changed renal clearance, which is indicated by the reduction of the total plasma clearance at about 53%. The combination IFN/FA did not show a similar effect. Yet, in both cases an improvement of the tumor response and of the clinical picture could be observed.

Aged↗
PubMed1991

[Comparative bioavailability of fluorouracil and its prodrug, ftorafur, following intra-arterial, intravenous and preoral administration].

The blood-plasma levels in 28 patients, suffering from colorectal cancer with liver metastases, which were treated by a cyclic chemotherapy with fluorouracil (1) after p.o. and intraarterial (i.a.) administration of 1 or its prodrug ftorafur (2), respectively, were compared with those obtained after i.v. administration and the pharmacokinetics were calculated. In the case of 1 as well as of 2 the i.a. administration has been found to be optimal for distribution into the tumor tissue of liver metastases due to lowered blood-plasma concentrations. The absolute bioavailability, was 78% for p.o. and 57% for the i.a. administration of 1 respectively, and 98% for p.o. and 61% for the i.a. administration of 1 (given as 2), Accordingly, p.o. administration of both substances leads to therapeutical sufficiently high plasma levels with a steady state of css = 2.9 micrograms/ml/tss = 14 min for 1 and css = 3.5 micrograms/ml/tss = 20 min for 2.

Administration, Oral↗
PubMed1990

[Pharmacokinetic aspects of dosage increase of recombinant interferon alpha-2B in patients following intraperitoneal and intra-arterial application].

Interferon-alpha-2 b (IFN) was administered as an i.a. bolus at doses of 3 and 5 million international units (MIU), as an i.a. 24h long-time infusion at 3 and 5 MIU and as an i.p. 90 min short-time infusion at 5, 10 and 15 MIU. Dose escalation of IFN on i.p. administration leads to correspondingly elevated AUC values of IFN (correlating to the dose) in the peritoneal fluid (PF) and blood, with a shift of the steady-state at about 2h. Bioavailability of IFN is 30 times higher for PF than for blood. t1/2 el, Vd and total clearance are not influenced by dose escalation in both compartments due to their dose-independency. IFN is eliminated from the PF with t1/2 el = 10-32h and from the blood with t1/2 el = 5-13h. After an i.a. bolus at either dosage IFN is distributed from the blood with a half-life of below 2h. 24h infusion leads to a steady-state within 4-6h and a cmax of 8.5 or 12.5 units/ml, respectively. IFN is slowly eliminated during infusion with a t1/2 el of 16h.

Dose-Response Relationship, Drug↗
PubMed1987

Determination of thalidomide and its major metabolites by high-performance liquid chromatography.

A rapid and sensitive isocratic high-performance liquid chromatography assay for the simultaneous and quantitative determination of thalidomide (alpha-phthalimidoglutarimide) and its major metabolites from human serum has been developed. The parent compound and the metabolites can be efficiently separated by reversed-phase chromatography using tetramethylammonium bromide as an ion-pair-forming reagent.

Biotransformation↗
PubMedDate not supplied

Pharmacokinetics of mitomycin C in patients after bolus injection and chemobolisation of the hepatic artery with Spherex starch particles.

The pharmacokinetics of mitomycin C after chemobolisation of the common hepatic artery by micronized Spherex starch particles (mean particle size 30 microns) were investigated in 5 cancer patients. Bolus injection and simultaneous occlusion of the artery lead to a significantly lower systemic circulation of mitomycin C in the blood vessel system than after bolus injection without chemobolisation. The plasma concentration-time curves showed lower values in the alpha-phase in the presence of Spherex (co = 743 ng/ml) than without starch particles (co = 987 ng/ml). Accordingly, the AUC values were significantly lower too (AUC = 28.6 micrograms/ml.h with Spherex and 39.7 micrograms/ml.h without Spherex), thus leading to a lower systemic bioavailability of the drug and a higher local bioavailability in the tumor region. Elimination of mitomycin from the central compartment was similar for both administrations (t1/2 = 27 min with Spherex and 28 min without Spherex) and showed the characteristic profile of the substance. The clinical picture showed a milder toxicity with a certain loss of side effects. These results indicate a significant and desirable change in the pharmacokinetics of mitomycin C during the distribution phase into the tissue of patients.

Aged↗