Abstract:Objectives: The aim of our study was to evaluate impact of CYP2D6 and MDR1 polymorphisms on the analgesic effi cacy of tramadol in patients after a knee arthroscopy. Background : Pharmacokinetics of tramadol and its metabolites is stereoselective and displays high interindividual variability correlating with polymorphic CYP2D6 in the population. Available data provide controversial results regarding the analgesic effi cacy of tramadol in subjects with different CYP2D6 genotypes. Methods: Pain intensity was assessed using visual analogue scale at 2 and 24 hours after the knee arthroscopy in 156 patients. Polymorphisms CYP2D6*3,*4,*5,*6, and gene duplication and C3435T in MDR1 gene were analyzed by PCR -RFLP. Results: Mean VAS 2h value in the whole study group was 44.0 ± 16.5 mm. Mean pain difference, was lowest in the UM group and highest in the PM group. The pain difference varied signifi cantly among the CYP2D6 subgroups (F = 4.29; p = 0.006) with signifi cant differences between homEM vs hetEM, homEM vs PM, and UM vs PM subgroups. There were no signifi cant differences among MDR1 subgroups with regards of pain difference. Mean tramadol consumption was 2.47 ± 1.17 mg/kg during the 24 h period. There were no signifi cant differences in the drug consumption, reporting of adverse reactions, need for rescue analgesic medication or verbal description of pain among the CYP2D6 or MDR1 genotype subgroups. Conclusion: CYP2D6 plays a signifi cant role in tramadol analgesic effi cacy. The non-opioid analgesia in PMs was associated with better subjective pain relief in patients after a knee arthroscopy (Tab. 3, Ref. 18). Full Text in PDF www.elis.sk.

The pharmacodynamic effects of tramadol were easily detected using both static and dynamic pupil parameters. The pharmacodynamic profiles were markedly influenced by the CYP2D6 phenotype.

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The trial involved eleven 10-month-old green iguanas (Iguana iguana rhinolopha, 5 males/6 females) from a single clutch of captive breeding program. Lizards were housed in an experimental room and maintained in terraria (75 cm × 85 cm × 85 cm), with a constant light/temperature/air humidity regime (12 h/12 h, 24-35 °C, 60-80%). The body condition and health status of the iguanas was monitored at regular intervals. At the age of 34 months three females laid eggs spontaneously whereas the other three females suffering from pre-ovulatory follicle stasis (POFS) were ovariectomized (OVE) at the end of 35 months. Within the period of the reproductive activity (February -March, November-January) plasma concentrations of calcium, cholesterol and triglycerides were significantly higher (p < 0.05) in females than in males. Significantly higher concentrations of calcium and triglycerides were found in plasma samples of POFS females than in healthy females after oviposition. Plasma concentrations of calcium, phosphorus, cholesterol and triglycerides were significantly higher in intact females than in OVE females. The mechanism of hormonal control for seasonal changes of calcium, cholesterol and triglyceride concentrations in blood of female green iguana remains to be examined in the future. Reptiles, calcium, cholesterol, triglycerides, vitellogenesis, follicular stasisPlasma biochemistry in green iguanas has been a subject of interest for a number of authors (Dessauer 1970;Anderson 1992;Barten 1993;Divers et al. 1996;Wagner and Wetzel 1999;Bruder 1998;Harr et al. 2001). Results of previous studies show a significant degree of variation due to different animal selection, methods and technical differences in blood sample treatment (Campbell 1996;Köhler 1996; R e dro be and MacDonald 1999; K ubalek 2000;Harr et al. 2001;Walton 2001;Barten 2002;Knotek et al. 2002;Jacobson 2003). Most trials so far consisted in analysing blood from one-off sample-takings. The goal of our trial therefore was performing a long-term study on blood-related animals kept under identical conditions. Materials and Methods AnimalsA group of eleven 10 months-old green iguanas (Iguana iguana rhinolopha, 5 males/6 females) from a single clutch of captive breeding program was included in this trial. Lizards were housed in an experimental room and maintained in terraria (75 cm × 85 cm × 85 cm), with a specific light regime (12h/12 h, 100 W bulb + UV lamp Repti-Glo, Hagen); iguanas housed in groups (two females and one male), the temperature ranged between 24 and 35 °C and air humidity between 60 and 80%. The iguanas were fed every day. The diet consisted of common dandelion leaves, carrots, tomatoes, fruits, lettuce, Chinese cabbage and cottage cheese mixed with calcium powder and pelleted commercial chow. Control of pregnancy, ovariectomyThe body condition and health status of the iguanas was monitored at regular intervals. The coelomic cavity was controlled manually with gently palpation of the body wall. At the age of 34 months three females laid fertile...

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 singlenucleotide polymorphisms (SNPs) have been noted, mainly in exons 3, 5, and 8. The most studied SNPs may lead to decreased enzyme activity and may have impact on drug metabolism. Variant alleles are called CYP2C8*2 (I269F), CYP2C8*3 (R139K, K399R), and CYP2C8*4(I264M). Our aim was to investigate the frequency of major functional SNPs among the Czech population. Material and methods: DNA was isolated from whole blood of 161 healthy, young, and unrelated subjects (94 men and 67 women, aged from 23 to 28 years). The genotypes of polymorphic positions CYP2C8*2, CYP2C8*3 (G416A, A1196G), and CYP2C8*4 were determined by polymerase chain reaction-restriction fragment length polymorphism. Results and conclusion: Observed allele frequencies were 10.9%, 5.9%, and 0.3% for the alleles CYP2C8*3, CYP2C8*4, and CYP2C8*2, respectively. Both CYP2C8*3 (G416A, A1196G) alleles have been found in complete linkage disequilibrium. The allele distribution complies well with Hardy-Weinberg equilibrium. Allele frequencies of functionally important CYP2C8 variants in the Czech population are similar to that of other Caucasian populations.

This paper reviews the impact of genetic variability of drug metabolizing enzymes, transporters, receptors, and pathways involved in chronic pain perception on the efficacy and safety of analgesics and other drugs used for chronic pain treatment. Several candidate genes have been identified in the literature, while there is usually only limited clinical evidence substantiating for the penetration of the testing for these candidate biomarkers into the clinical practice. Further, the pain-perception regulation and modulation are still not fully understood, and thus more complex knowledge of genetic and epigenetic background for analgesia will be needed prior to the clinical use of the candidate genetic biomarkers.

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Several candidate genes have been proposed as potential biomarkers for altered pharmacodynamics or pharmacokinetics of immunosuppressive drugs. However, there is usually only limited clinical evidence substantiating the implementation of biomarkers into clinical practice. Testing for thiopurine-S-methyltransferase polymorphisms has been put into routine clinical use quite widely, while the other pharmacogenetic tests are much less frequently used. Relatively good evidence appeared for tacrolimus-related biomarkers; thus, their utilization may be envisaged in the near future. Although the biomarkers related to mycophenolate, sirolimus or other drugs in the therapeutic class may be promising, further research is necessary to provide more robust evidence. The present review focuses on immunosuppressive drugs, excluding biological treatment.