Recent pre-clinical evidence suggests that the active metabolite of tamoxifen, endoxifen, is a substrate for efflux pump P-glycoprotein. The aim of our study was to evaluate, if the polymoprhisms within ABCB1 gene alter tamoxifen adjuvant treatment efficacy in premenopausal women. Totally 71 premenopausal women with estrogen receptor positive breast cancer indicated for tamoxifen adjuvant treatment were followed retrospectively for median period of 56 months. The gentic polymorphisms of CYP2D6 and ABCB1 were analyzed and potential covariates as tumor grading, staging, age at the diagnosis, comedication, quantitative positivity of ER or PR were also evaluated. Cox proportional-hazards regression model indicated that patients carrying at least one variant allele in ABCB1 rs1045642 had significantly longer time to event survival compared to wild type subjects. Non-significant trend was noted for better treatment outcome of patients carrying at least one variant allele in the SNP rs2032582, while for the CYP2D6 polymorphism poor metabolizer phenotype resulted in worse outcome in comparison to extensive metabolizers subjects with HR of 4.04 (95 % CI 0.31-52.19). Similarly, patients using CYP2D6 inhibitors had non-significantly shorter time-to-event as compared to never users resulting in hazard ratio of 2.06 (95 % CI 0.40-10.63). ABCB1 polymorphisms may affect outcome of tamoxifen adjuvant treatment in premenopausal breast cancer patiens. This factor should be taken into account in addition to the CYP2D6 polymorphism or phenotypic inhibition of CYP2D6 activity.

Genetic factors may contribute to the differential response to opioids. The aim of this study was to evaluate the association between polymorphisms of µ1-opioid receptor gene OPRM1 (rs1799971), and P-glycoprotein transporter gene ABCB1 (rs1045642, rs2032582), and piritramide efficacy under postoperative patient-controlled analgesia (PCA). In 51 patients, OPRM1 variant was associated with decreased efficacy in early postoperative period evidenced by sum of pain intensity difference in the 0-6 h postoperative period (SPID0-6), (F=3.27, p=0.029). Mean (SD) SPID0-6 was observed in the 118AA genotype 22.9 (6.1) mm, which was significantly higher from the 118GG genotype 10.0 (4.4) mm, p=0.006. The lowest cumulative dose was recorded in 118AA genotype 19.1 (9.8) mg, which was significantly less than in the 118GG genotype group 36.6 (6.1) mg, p=0.017. Opioid–induced adverse effects were observed in 11, 30, and 100 % of patients in 118AA, 118AG, and 118GG genotype groups, respectively (p<0.05). Piritramide efficacy and safety was not significantly affected by ABCB1 (rs1045642, rs2032582) polymorphisms. Variant OPRM1 118G allele is associated with decreased acute postoperative pain relief after piritramide. Decreased efficacy leads to higher drug consumption under PCA settings, which however, does not fully compensate insufficient pain relief, but increases incidence of adverse effects.

The aim of our study was to evaluate possible effect of ABCB1, and OPRM1 polymorphisms on the efficacy and safety of remifentanil in women undergoing elective cesarean section under general anesthesia. Women received remifentanil (1 µg/kg i.v.) 30 s prior to the induction to standardized general anesthesia. The ABCB1 (rs2032582, rs1045642) and OPRM1 (rs1799971) polymorphisms were analyzed from maternal peripheral blood. The basal hemodynamic and demographic parameters in the study population (n=54) were similar in all the subgroups. The median ± SD increase of systolic blood pressure at 5 min from the baseline was practically completely abolished in homozygous carriers of ABCB1 variants in comparison with wild-type subjects -2.67±25.0 vs. 16.57±15.7 mm Hg, p<0.05 for rs2032582, and 2.00±23.9 vs. 22.13±16.8 mm Hg, p<0.05, for rs1045642, respectively. While no neonate belonging to ABCB1 wild-type homozygous or OPRM1 variant carrying mothers needed any resuscitative measure, 10.5 % of the neonates belonging to OPRM1 wild-type homozygous mothers received resuscitative support similarly as 11.1 %, and 12.5 % of neonates of mothers carrying variants of rs2032582, and rs1045642, respectively. Decreased stabilizing effects of remifentanil on maternal hemodynamics has been observed in ABCB1 wild type mothers, while the adaptation of the neonates was clinically worse in OPRM1 wild type, and ABCB1 variant allele carriers.

No abstract

No abstract

Dopamine was shown to induce mydriasis by excitation of alpha-adrenergic receptors at the dilator pupillae muscle. Pupilla diameter may thus serve as an indirect measure of peripheral pharmacokinetics of L-DOPA and dopamine. The aim of this study is to evaluate the effect of L-DOPA dosage on pupillometric parameters in Parkinson's disease (PD) patients. Sixteen PD patients and 14 healthy control subjects (CS) were studied. The statistical analysis revealed significant differences between CS and PD patients for the mean maximum and minimum pupil diameters (p = 0.017, p = 0.028, respectively), with higher values found in PD. Moreover, a significant dose-response relationship was found between the maximum pupil diameter and both the morning L-DOPA dose (R = 0.78) and the total daily L-DOPA dose (R = 0.93). A sigmoid-shaped curve best describes the dose-response relationship, with a ceiling effect at about 400 mg L-DOPA daily dose. In conclusion, measuring pupillometric parameters represents a sensitive tool for non-invasive evaluation of the peripheral effect of L-DOPA, especially with daily doses below 400 mg L-DOPA.

The aim of this study was to evaluate the association between OPRM1 and ABCB1 polymorphisms on pain relief with epidural sufentanil in 69 patients after rectosigma resection for cancer. The median number of injections (SD) 2.31 (1.36), IQR=1, required by 118AA subjects was significantly lower in comparison with 118AG group 5.25 (3.13), IQR=6.5, (χ2=9.75, p=0.001); correspondingly median drug consumption of 1.16 (0.79), IQR=1.083, defined daily doses (DDD) was significantly less in the 118AA group in comparison with 2.14 (1.17), IQR=2.23, DDD in 118AG subjects, (χ2=7.00, p=0.008). Opioid-induced adverse effects were observed in 15 % and 33 % of patients in 118AA and 118AG groups, respectively (χ2=8.16, p=0.004). The median number of injections (SD) required by women and men was 3.30 (2.16), IQR=2, and 2.80 (1.59), IQR=1, respectively (χ2=6.25, p=0.012). Opioid-induced adverse effects were observed in 26 % and 12 % of women and men, respectively (χ2=5.49, p=0.011). Heterozygotes of OPRM1 polymorphism and women were more difficult to treat subpopulations that required higher doses of rescue analgesic medication and suffered more adverse effects.

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. Results. Median (IQR) piritramide consumption was 18.5 (13.5-31.2) and 15.0 (15.0-15.0) mg in the PCA and IM groups, respectively (P=0.0092). The respective values of area under the VAS 2-16 -time curve were 40 and 280 mm.h (P=0.0027). Opioid-induced adverse effects were more frequent in the PCA than in the IM group. Variant OPRM1 allele was associated with decreased pain relief, increased opioid consumption and increased incidence of adverse effects, while ABCB1 polymorphisms showed no impact on the observed parameters. Conclusions. We observed higher piritramide consumption, better pain relief and slightly worse safety profile in the PCA group compared with IM administration. Variant OPRM1 118G allele carriers required higher opioid dosing and suffered from more adverse effects, however, the differences between genotypes have been less pronounced in the PCA patients likely due to improved pain management via PCA.