Analgesic effects of piritramide in acute postoperative pain - comparison of intramuscular administration with patient-controlled intravenous analgesia and impact of OPRM1 and ABCB1 polymorphisms.

Aims: The aim of this study was to compare the efficacy, consumption and safety after piritramide administered either intramuscularly (IM) on demand or via patient-controlled intravenous analgesia (PCA) and to examine the impact of OPRM1 and ABCB1 gene polymorphisms on the drug efficacy/safety in both regimens.

Methods: One hundred and four patients scheduled for elective inguinal hernioplasty received piritramide with PCA or IM for postoperative pain management. We evaluated piritramide consumption, pain intensity using visual analogue scale (VAS) and adverse effects.

Impact of smoking on metabolic changes and effectiveness of drugs used for lung cancer.

Objective: This article reviews the published studies dealing with the influence of cigarette smoking on metabolic changes and effectiveness of drugs used in the systemic chemotherapy of the lung cancer.

Methods: The literature search of interactions between cigarette smoking and drugs used for lung cancer was carried out. The abstracted data mostly involved some induction of key drug-metabolizing enzymes of cytochrome CYP1A1/2, CYP2D6, CYP3A4 and isoforms of UDP-glucuronosyltransferase.

Treatment of tobacco dependence as a standard part of oncology care.

After the oncological diagnosis, smoking has a major impact on survival, course and effectiveness of oncology treatment, and quality of the further life. Smoking worsens surgery outcomes, reduces the effectiveness of radiation therapy and chemotherapy, increases the risk of side effects of oncology treatment, and increases the incidence of tumor duplication or other comorbidities like venous thrombosis, cardiovascular diseases or infections. The article contains a summary of practical recommendations for oncology patients, including smoke-free environments, the importance of zero exposure to tobacco smoke, clear advice to stop smoking to smokers and offer of tobacco dependence treatment.

[Smoking and pharmacological interactions].

Cigarette smoking can affect drug metabolism via pharmacokinetic and pharmacodynamic mechanisms, and a sudden change in smoking status can render patients at risk of serious adverse reactions, eg. after clozapine. Patients should be regularly monitored with regard to their smoking status and extent of cigarette consumption and doses of relevant medications adjusted accordingly.

Pleiotropic effects of niacin: Current possibilities for its clinical use.

Niacin was the first hypolipidemic drug to significantly reduce both major cardiovascular events and mortality in patients with cardiovascular disease. Niacin favorably influences all lipoprotein classes, including lipoprotein[a],and belongs to the most potent hypolipidemic drugs for increasing HDL-C. Moreover, niacin causes favorable changes to the qualitative composition of lipoprotein HDL.

Niacin in the Treatment of Hyperlipidemias in Light of New Clinical Trials: Has Niacin Lost its Place?

Niacin is considered to be a powerful drug for the treatment of lipid and lipoprotein abnormalities connected with "residual cardiovascular risk", which persist in high-risk patients even when the target goals of LDL-C are achieved with statin therapy. Recent large randomized clinical studies - AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides) and HPS2-THRIVE (Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) - delivered some disappointing results, leading to the conclusion that no further benefit (decreased parameters of cardiovascular risk) is achieved by adding niacin to existing statin therapy in patients with high cardiovascular risk. Moreover, in these studies, several adverse effects of the treatment were observed; therefore, niacin treatment for hypolipidemias is not recommended.

Nabumetone and 6-MNA Pharmacokinetics, Assessment of Intrasubject Variability and Gender Effect.

In this open-label, laboratory-blinded, 2-way single dose study in 24 volunteers of both sexes we found that (1) nabumetone reaches mean Cmax ± SD of 0.56 ± 0.20 mg·L at mean tmax of 8.

Lipid-lowering effect of fluvastatin in relation to cytochrome P450 2C9 variant alleles frequently distributed in the Czech population.

Background: CYP2C9*3 allele has been reported to correlate with increased plasma concentration of fluvastatin active form in healthy volunteers. We analyzed the correlation between the CYP2C9 genotype and cholesterol-lowering effect of fluvastatin in human hypercholesterolemic patients.

Material/methods: The study was prospective, without any interventions to standard procedures of hypolipidemic treatment.

Genetic polymorphisms of CYP2C8 in the Czech Republic.

Aim: CYP2C8 represents 7% of the hepatic cytochrome system and metabolizes around 5% of drugs in phase I processes. It also plays a significant role in metabolism of endogenous compounds. More than 20 single-nucleotide polymorphisms (SNPs) have been noted, mainly in exons 3, 5, and 8.

[Our experience with maraviroc treatment in HIV positive patients].

Unlabelled: BACKGROUND; Although antiretroviral therapy has changed the clinical course of HIV infection, AIDS remains an incurable disease. Virus entry inhibitors, including maraviroc as the only registered representative of the class, represent a newly emerged group of anti-retrovirals with novel mechanism of action. The primary endpoint is to evaluate the clinical efficacy parameter of maraviroc by measuring viral load at the end of the 4 week treatment period.

[Determination of nabumetone and 6-methoxy-2-naphthylacetic acid in plasma using HPLC with UV and MS detection].

The study aimed to establish and validate an analytical method for the determination of nabumetone and 6-methoxy-2-naphthylacetic acid (6-MNA) in human plasma after a single therapeutic dose of the drug. Two methods based on HPLC with UV and MS detection were compared. Optimal results in sample preparation were achieved using solid phase extraction.

[Infrared pupilometry as a biomarker of drug effects].

Background: Measurement of the size of the pupil is used as a biomarker of drug efficacy, assessing mainly their effect on the central nervous system. The aim of our study was to evaluate sensitivity of various pupilometric parameters as biomarkers of widely used opioid analgesic drug tramadol.

Methods And Results: Pharmacodynamic action of tramadol drops given orally in standardized dose of 0.

Cytochrome P450 2D6 polymorphism and drug utilization in patients with oral lichen planus.

Objective: Oral lichen planus (OLP) is one of the commonest diseases of the oral mucosa. The etiology of the disease is unknown. Our goal was to determine frequencies of functionally important alleles which determine the metabolic rate (phenotype) of individuals with OLP and to compare drug utilization, with focus on CYP2D6, with that of a control group.

Enantiomeric determination of tramadol and O-desmethyltramadol in human plasma by fast liquid chromatographic technique coupled with mass spectrometric detection.

A rapid and sensitive method using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for enantiomeric determination of tramadol and its primary phase metabolite O-desmethyltramadol in human plasma has been developed. Tramadol hydrochloride-(13)C, d(3), was used as an isotopic labeled internal standard for quantification. The method involves a simple solid phase extraction.

Human urinary metabolomic profile of PPARalpha induced fatty acid beta-oxidation.

Activation of the peroxisome proliferator-activated receptor alpha (PPARalpha) is associated with increased fatty acid catabolism and is commonly targeted for the treatment of hyperlipidemia. To identify latent, endogenous biomarkers of PPARalpha activation and hence increased fatty acid beta-oxidation, healthy human volunteers were given fenofibrate orally for 2 weeks and their urine was profiled by UPLC-QTOFMS. Biomarkers identified by the machine learning algorithm random forests included significant depletion by day 14 of both pantothenic acid (>5-fold) and acetylcarnitine (>20-fold), observations that are consistent with known targets of PPARalpha including pantothenate kinase and genes encoding proteins involved in the transport and synthesis of acylcarnitines.

Enatiomeric determination of tramadol and O-desmethyltramadol in human urine by gas chromatography-mass spectrometry.

A GC-MS assay for stereoselective determination of tramadol and its pharmacologically active phase I metabolite O-desmethyltramadol in human urine was developed. Nefopam was used as internal standard. The method involves a simple solid phase extraction with chiral analysis by gas chromatography-electron ionization mass spectrometry using m/z 263; 58, 249; 58, and 179; 58 for the determination of concentration of tramadol, O-desmethyltramadol and internal standard, respectively.

Polymorphisms of the TPMT gene in the Czech healthy population and patients with inflammatory bowel disease.

Genetic variation in thiopurine S-methyltransferase (TPMT) is a major factors for wide variation in the metabolism and safety of thiopurine drugs. We investigated the frequency of functional gene polymorphisms in 396 patients with inflammatory bowel disease and 300 healthy subjects. Frequencies of functionally deficient alleles TPMT*2, TPMT*3A, TPMT*3B, and TPMT*3B in the patient group were 0.

Frequency of single nucleotide polymorphisms of CYP2D6 in the Czech population.

CYP2D6 is a member of cytochrome P450 enzymes that metabolise over 25% of commonly used drugs. Genetic polymorphisms can cause insufficient drug efficacy at usually administered doses or can be the cause of adverse drug reaction. CYP2D6 genotyping can be used to predict CYP2D6 phenotype and thereby explain some abnormalities in drug response and thus optimize pharmacotherapy.

3,4-Dehydrodebrisoquine, a novel debrisoquine metabolite formed from 4-hydroxydebrisoquine that affects the CYP2D6 metabolic ratio.

Considerable unexplained intersubject variability in the debrisoquine metabolic ratio (urinary debrisoquine/4-hydroxydebrisoquine) exists within individual CYP2D6 genotypes. We speculated that debrisoquine was converted to as yet undisclosed metabolites. Thirteen healthy young volunteers, nine CYP2D6*1 homozygotes [extensive metabolizers (EMs)] and four CYP2D6*4 homozygotes [poor metabolizers (PMs)] took 12.

Pharmacokinetic conversion study of a new cyclosporine formulation in stable adult renal transplant recipients.

Cyclosporine A (CyA) is a standard component of immunosuppressive regimens. It is a critical-dose drug for which a minor change in absorption can have important clinical consequences. The aim of the study was to compare the pharmacokinetics and safety of the new generic CyA formulation, Equoral capsules, after a switch from original formulation, Neoral capsules, in seventy stable adult renal transplant recipients.

Minipig as a model for drug metabolism in man: comparison of in vitro and in vivo metabolism of propafenone.

To prove the suitability of minipigs as experimental animal in modeling of the drug metabolism and pharmacokine-tics in man, propafenone metabolism in vitro at the microsomal level as well as propafenone pharmacokinetics in the minipig was studied. The results were compared with those obtained for humans. It can be concluded that whereas the microsomal in vitro system of minipig may be a good model for drug metabolism in the man, the pharmacokinetics in the whole organism is more complex reflecting differences in substrate specificities of many enzymatic and transport systems.