Determination of rhodamine 123 by sequential injection technique for pharmacokinetic studies in the rat placenta.

The sequential injection (SIA) technique was applied in pharmacokinetic studies of the transporter-mediated passage of a model substrate, rhodamine 123 (Rho123), through the dually perfused rat term placenta. The method described was used for real-time monitoring of Rho123 concentrations in both the maternal and fetal compartments. Determination was processed by fluorescence detection (lambda(ex)=480 nm, lambda(em)580 nm); calibration curve was linear over the range 0.

Examination of Glucocorticoid receptor alpha-mediated transcriptional regulation of P-glycoprotein, CYP3A4, and CYP2C9 genes in placental trophoblast cell lines.

The placental trophoblast at different stages of pregnancy contains some drug transporters and xenobiotic-metabolising enzymes, as well as ligand-activated nuclear receptors, which control their inducible transcriptional regulation. Glucocorticoid receptor alpha (GRalpha) is expressed in both placental syncytiotrophoblast and cytotrophoblast. GRalpha was shown to control inducible expression of several enzymes of the cytochrome P-450 family (CYP) and the drug transporter P-glycoprotein in the liver.

Expression and transport activity of breast cancer resistance protein (Bcrp/Abcg2) in dually perfused rat placenta and HRP-1 cell line.

Breast cancer resistance protein (BCRP/ABCG2) is a member of the ATP-binding cassette transporter family that recognizes a variety of chemically unrelated compounds. Its expression has been revealed in many mammal tissues, including placenta. The purpose of this study was to describe its role in transplacental pharmacokinetics using rat placental HRP-1 cell line and dually perfused rat placenta.

Lack of interactions between breast cancer resistance protein (bcrp/abcg2) and selected antiepileptic agents.

Purpose: Recent studies have indicated constitutive expression of efflux transporter, breast cancer resistance protein (BCRP, ABCG2), in endothelial cells of the blood-brain barrier (BBB). In epileptogenic brain tumors such as ganglioma, astrocytoma, anaplastic astrocytomas, or glioma multiforme, strong expression of BCRP in the microvasculature of the BBB was observed. Therefore it was hypothesized that this phenomenon could critically influence the bioavailability of drugs in these tumors and potentially contribute to the failure of antiepileptic treatment.

Corticosterone transfer and metabolism in the dually perfused rat placenta: effect of 11beta-hydroxysteroid dehydrogenase type 2.

Although rat is the most widely used model of glucocorticoid programming of the fetus, the role of rat placental 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) in the transplacental pharmacokinetics of the naturally occurring glucocorticoid, corticosterone, has not yet been fully elucidated. In this study, expression of 11beta-HSD2 in the rat placenta on two different gestation days (16 and 22) was examined using quantitative RT-PCR and Western blotting, and dually perfused rat term placenta was employed to evaluate its functional capacity to transfer and metabolize corticosterone. Marked decrease in placental expression of 11beta-HSD2 toward term was observed on both mRNA and protein levels.

P-glycoprotein expression and distribution in the rat placenta during pregnancy.

P-glycoprotein (P-gp) is a drug efflux transporter that limits the entry of various potentially toxic drugs and xenobiotics into the fetus and is thus considered a placental protective mechanism. In this study, P-gp expression was investigated in the rat chorioallantoic placenta over the course of pregnancy. Three methods have been employed: real-time RT-PCR, western blotting and immunohistochemistry.

Examination of the functional activity of P-glycoprotein in the rat placental barrier using rhodamine 123.

Rhodamine 123 (Rho123), a model substrate of P-glycoprotein (P-gp), was used to evaluate the functional activity of P-gp efflux transporter in the rat placental barrier. The dually perfused rat-term placenta method was used. In our experiments, the materno-fetal transplacental passage of Rho123 did not meet the criteria of the first-order pharmacokinetics, suggesting an involvement of transporter-mediated process.

[Physiologic function of P-glycoprotein].

P-glykoprotein has been proposed to function as a membrane transport protein for a large variety of substrates, ranging from small lipophilic molecules, steroid hormones, lipophilic peptides, some drugs, biologically important molecules and xenobiotics. There is little doubt that P-glycoprotein transports a wide range of substrates out of cells, nevertheless it is difficult to explain its wide substrate specificity and mechanism of the transport. P-glycoprotein has been found to be a major cause of acquired multidrug resistance (MDR) of cancer cells to chemotherapeutic drugs.

Influence of P-glycoprotein on the transplacental passage of cyclosporine.

The transfer kinetics of cyclosporine across the dually perfused rat placenta in the maternal to fetal direction and a possible involvement of P-glycoprotein were investigated. The transplacental clearance of cyclosporine in the materno-fetal direction was found to be dependent on the maternal inflow concentration of cyclosporine. Coadministration of cyclosporine with an excess of quinidine or chlorpromazine into the maternal compartment revealed 1.

[Metamizol--a new effective analgesic with a long history. Overview of its pharmacology and clinical use].

Metamizol is an effective, non-opioid analgesics which was originally introduced to the therapy in the year 1922. However, with the reference to the side effects of other related pyrazolone derivatives its administration, similarly as the usage of other pyrazolones, was significantly limited. Later, metamizol has been used, usually mixed, with spasmolytic agents and quite recently it has been introduced as a mono-component medicament.

[Effective and safe pharmacotherapy of acne vulgaris and treatment of sun-damaged skin].

An inevitable condition for the pharmacist is a basic knowledge of dermatological changes which are prominent in acne and solar impairment of the skin to be able to recommend in a qualified manner an effective and safe treatment to the patient. However, sufferers of the more serious forms of acne should always be referred to their general practitioner, or preferentially a dermatologist. Acne vulgaris is an androgen-induced disorder, but three major mechanisms for the development of the disease have been identified: hypertrophy of the sebaceous gland, hyperkatosis of the follicular epithelium, and proliferation of microbial flora, particularly Propionibacterium acnes.

[Common gastrointestinal symptoms and their effective and safe treatment].

The pharmacist is an important specialist in the selection of the drug when the patient comes for pharmacist's advice of how to alleviate common gastrointestinal symptoms. Of all drugs which can be effective in these situations, only three drugs (bismuth subsalicylate, psyllium, and docusate sodium) proved to be advantageous for self-medication. Bismuth subsalicylate (BSS) is much appreciated in the treatment of peptic ulcers where it not only covers the base of the ulcer but also eradicates Helicobacter pylori.

[Self-medication of the common cold].

Self-medication can be useful in the multisymptomatic management of the common cold and other preferentially non-febrile flu-like symptoms, especially as at present multicomponent remedies are available, which may make self-medication significantly easier with consequent better compliance of adult patients. Children, on the contrary, are not suitable acceptants of self-medication mediated by their parents because the sickness exhibits in children nearly exclusively febrile progress. The procedure of the therapy to be really effective and safe must be necessarily concentrated into pharmacies, where safety and efficacy of therapy are ensured by the pharmacist as the last link of contact between the patient and the drug.

Pharmacokinetic examination of antipyrine passage through the placenta and the small intestine in rats.

The placental and small intestinal barriers, though obviously different, show many functional as well as morphological similarities. When the surface area of both barriers in man was recalculated to a unit of body weight, nearly identical values (2.71 and 2.

Different transfers of N-acetyl-p-aminobenzoic acid and p-aminobenzoic acid across the placenta and the small intestine in rats.

The aim of the present study was to evaluate the transfer of N-acetyl-p-aminobenzoic acid (AcPABA) across the rat term placenta and the rat small intestine and to compare it with that of its parent drug p-aminobenzoic acid (PABA). Umbilical perfusion of the rat term placenta was used to determine the materno-fetal transfer. AcPABA appeared in the fetal compartment significantly more slowly than PABA (k transfer = 0.

Unidirectional transfer of D-xylose across the rat placenta.

1. The transplacental transfer of D-xylose was investigated in the present study. 2.

Phenytoin transfer across the in situ perfused rat term placenta.

Transfer of phenytoin (PHT) across the rat term placenta perfused in situ was investigated and compared with that of antipyrine (AP) as a marker of passive diffusion. PHT was shown to cross the placenta with similar kinetics as AP did. Both the first order transfer constant (ktr = 0.

Pharmacokinetic examination of p-aminobenzoic acid passage through the placenta and the small intestine in rats.

In the present study the permeability of the rat small intestine and the placenta to p-aminobenzoic acid (PABA) and antipyrine (AP) was investigated. Perfusion of the rat term placenta was used to determine the materno-fetal transfer of both compounds. PABA appeared in the fetal compartment faster than AP (ktransfer = 0.

Mechanisms of action of some air pollutants on the airways.

Common air pollutants (O3, SO2) exert their deleterious effects in several ways, mostly on the respiratory functions. Ozone causes formation of peroxides and aldehydes with subsequent release of inflammatory lipids and cytokines. Changes in the activity of neutral endopeptidase and release of neuropeptides may occur.

Analysis of pharmacotherapy of hypertension in out-patients.

In the present pilot study an attempt was made to evaluate the usefulness of results obtained about the treatment of patients suffering from high blood pressure for a pharmacoepidemiological study of the therapeutic value of antihypertensive agents. Data from 90 hypertensive patients were used in the present retrospective-prospective study. These patients all attended an out-patient clinic located in one of the East-Bohemian districts that are participating in the MONICA programme.

Pharmacokinetic parameters of verapamil and its active metabolite norverapamil in patients with hepatopathy.

Verapamil (CAS 52-53-9) is a calcium channel blocker with a vasodilatatory effect. Because of its significant first-pass effect, verapamil might be advantageous in the treatment of portal hypertension. It does not produce any excessive systemic effects, provided the doses are suitably adjusted.

Intestinal absorption of tolfenamic acid at experimental malabsorption states in rats.

Absorption kinetics of 14C-labelled N-(3-chloro-o-tolyl)-anthranilic acid (tolfenamic acid, 14C-TA, Clotam) from the small intestine was studied in intact rats and in rats with malabsorption states provoked by methotrexate, starvation, and triparanol. 14C-TA was administered intravenously and intraduodenally, and the drug concentrations in the blood were followed up radiometrically. A multi-compartmental model was applied for mathematical analysis.