OBJECTIVES: The aim of prospective study was to evaluate the therapeutic efficacy of piritramide in patients after removal of parathyroid glands in relation to MDR1 genotype. In the treatment of moderate acute postoperative pain, piritramide plays a major role. It is difficult to predict its optimal therapeutic efficacy and tolerability in individual patients. METHODS: We compared the effect of piritramide in 56 patients after surgical removal of parathyroid glands in a prospective study. We evaluated pain intensity, pain difference and sum of pain difference (SPID) using visual analogue scale (VAS in mm) and adverse effects in the relationship with the MDR1 - polymorphism of G2677T/A. RESULTS: In the wild-type group (2677GG), there was maximal pain difference of 30.6 ± 24.9 and SPID of 209.33 ± 95.80 while in genotype 2677TT and 2677GT, the corresponding values were 19.5 ± 25.5 and 147.07 ± 91.38, respectively. In group of patients with wild type of 2677GG genotype, there was 80 % of responders with more than 50 % reduction in VAS as compared to baseline while in group with carriers of 2677T allele, there are only 39 % of responders present (χ² = 5. 83; p = 0.016). Furthermore, the total consumption of piritramide was lower in comparison with the variant-allele carrying group (p = 0.008). The total incidence of adverse drug reactions was observed in 40 % of patients with wild type of 2677GG genotype when compared to 83% in the group carrying the variant allele (χ² = 7.92; p = 0.005). Significantly more patients in the wild-type group were satisfied with postoperative pain treatment in comparison to the variant allele group (χ² = 6. 49; p = 0.0109). CONCLUSION: We observed a better analgesic effect of piritramide and a decreased incidence of side effects in the wild-type genotype (2677GG) group, when compared with variant-allele carrying patients (Tab. 2, Fig. 1, Ref. 7).
- MeSH
- lidé středního věku MeSH
- lidé MeSH
- měření bolesti * MeSH
- opioidní analgetika terapeutické užití MeSH
- P-glykoprotein genetika MeSH
- paratyreoidektomie MeSH
- pirinitramid terapeutické užití MeSH
- polymorfismus genetický * MeSH
- pooperační bolest farmakoterapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: The aim of our study was to evaluate impact of CYP2D6 and MDR1 polymorphisms on the analgesic efficacy 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 efficacy 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 VAS2h 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 significantly among the CYP2D6 subgroups (F = 4.29; p = 0.006) with significant differences between homEM vs hetEM, homEM vs PM, and UM vs PM subgroups. There were no significant 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 significant 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 significant role in tramadol analgesic efficacy. The non-opioid analgesia in PMs was associated with better subjective pain relief in patients after a knee arthroscopy (Tab. 3, Ref. 18).
- MeSH
- artroskopie MeSH
- cytochrom P-450 CYP2D6 genetika MeSH
- dospělí MeSH
- frekvence genu MeSH
- heterozygot MeSH
- kolenní kloub chirurgie MeSH
- lidé středního věku MeSH
- lidé MeSH
- měření bolesti MeSH
- opioidní analgetika terapeutické užití MeSH
- P-glykoprotein genetika MeSH
- polymorfismus genetický MeSH
- pooperační bolest farmakoterapie MeSH
- tramadol terapeutické užití MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
WHAT IS KNOWN AND OBJECTIVE: The opioid effect of tramadol, which can be detected by pupillary response, is predominantly mediated by the O-demethylated metabolite, formed via CYP2D6. This study was designed to evaluate the effects of tramadol using different parameters of pupillometry as biomarkers. METHODS: Sixty-nine healthy volunteers received tramadol hydrochloride drops orally at a dose of 0·7 mg/kg. Pre-dose and 2-h post-dose pupillometric measurements were performed. The polymorphism of CYP2D6 was analysed. RESULTS AND DISCUSSION: Large interindividual variability was observed in the tramadol-induced pupillary reaction. Miosis was induced in 69·6% and mydriasis in 30·4% of the subjects. The pupillary response differed in relation to the CYP2D6 genotype. A maximal difference in initial pupil diameter of 0·81 mm was found in extensive metabolizers. There were significant effects observed on the pupillary light reflex parameters with tramadol administration (P < 0·05) except for the reflex amplitude and constriction velocity. WHAT IS NEW AND CONCLUSION: 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.
- MeSH
- aplikace orální MeSH
- biomarkery farmakologické metabolismus MeSH
- cytochrom P-450 CYP2D6 genetika metabolismus MeSH
- dospělí MeSH
- lidé MeSH
- mióza chemicky indukované MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mydriáza chemicky indukované MeSH
- opioidní analgetika aplikace a dávkování farmakokinetika farmakologie MeSH
- polymorfismus genetický MeSH
- pupila účinky léků MeSH
- tramadol aplikace a dávkování farmakokinetika farmakologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky kontrolované MeSH
- práce podpořená grantem MeSH
- MeSH
- adhezivita trombocytů MeSH
- Bernardův-Soulierův syndrom diagnóza MeSH
- glykoproteiny membrány trombocytů MeSH
- lidé MeSH
- senioři MeSH
- trombocyty patofyziologie patologie MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- MeSH
- chromozomy MeSH
- prasata MeSH
- sexuální diferenciace fyziologie genetika MeSH
- skot MeSH
- Check Tag
- skot MeSH
