Association between 8 P-glycoprotein (MDR1/ABCB1) gene polymorphisms and antipsychotic drug-induced hyperprolactinaemia

INTRODUCTION: Hyperprolactinaemia, a common adverse effect of antipsychotic drugs, is primarily linked to blockade of dopamine D2 receptors in the pituitary gland. Certain antipsychotic drugs, such as, for example risperidone and paliperidone, are more likely to induce hyperprolactinaemia compared to others. This effect is probably caused by a relatively high blood/brain concentration ratio, a consequence of being a substrate of P-glycoprotein. Genetic variants of P-glycoprotein with changed functional activity might influence the potential of risperidone and paliperidone to cause hyperprolactinaemia as the altered blood/brain concentration ratio would lead to a reduced therapeutic drug level within essential brain areas making dose adaptations necessary. This increases exposure of dopamine D2 receptors within the pituitary gland. AIMS: To investigate possible associations between MDR1/ABCB1 gene polymorphisms and antipsychotic drug-induced hyperprolactinaemia in Russian patients with schizophrenia and to determine possible differences between risperidone/paliperidone and other antipsychotics. METHODS: In total, 446 patients with schizophrenia were included from 3 psychiatric hospitals in Siberia. Blood samples were obtained in a cross-sectional study design for DNA extraction and prolactin measurement. Associations between hyperprolactinaemia and 8 MDR1/ABCB1 gene-polymorphisms were assessed using logistic regression analysis accounting for covariates. The analysis was repeated in a patient subgroup using risperidone or paliperidone. RESULTS: We did not observe an association between any of the 8 single nucleotide polymorphisms and the prevalence of antipsychotic-induced hyperprolactinaemia in the total patient population. However, in the risperidone/paliperidone subgroup, the single nucleotide polymorphism rs2032582 (G2677T) was found to be negatively associated with risperidone/paliperidone-induced hyperprolactinaemia. CONCLUSION: This study revealed a significant association between the ABCB1 gene polymorphism rs2032582 (G2677T) and risperidone/paliperidone-induced hyperprolactinaemia

The relationship between the use of flucloxacillin, vancomycin, aminoglycosides and ciprofloxacin and the susceptibility patterns of coagulase-negative staphylococci recovered from blood cultures.

Antibiotic use is a cause of selection of multiresistant bacterial strains. Over three years (1990-1992) we studied the relation between the use of flucloxacillin, vancomycin, aminoglycosides and ciprofloxacin and the susceptibility of coagulase-negative staphylococci (CNS) recovered from blood cultures. Although there was no increase in the use of flucloxacillin, the susceptibility of CNS to this antibiotic decreased from 25% to 6%. No increase in aminoglycoside use was seen, though the use in the non-surgical intensive care unit was 40 times the average use in the hospital. The susceptibility to gentamicin declined from 36% to 15% for the rest of the hospital and to zero for the npn-surgical intensive care unit. Vancomycin use did not change in the hospital as a whole, but the use in the haematological unit was about ten times that in the rest of the hospital. No single resistant strain (vancomycin MIC greater than or equal to 4 mg/L) was found. A three-fold increase in ciprofloxacin use was seen. After a decline in the susceptibility to ciprofloxacin from 72% to 58% in 1991, there was a small recovery to 62% in 1992. The use in the haematological unit was about 20 times that in the rest of the hospital. Ciprofloxacin susceptibility declined from 40% to 25% in that unit in 1991. In 1992 there was a small recovery to 29%

I-131 HIPPURAN FOR THE ESTIMATION OF RENAL PLASMA-FLOW - REQUIREMENTS FOR RADIOCHEMICAL PURITY

For many years iodide-131 Hippuran has been used as a tracer to measure effective renal plasma flow (ERPF). Because of the low renal clearance of free I-131-iodide and the inability to count it separately from I-131-Hippuran, free I-131-iodide will lower the calculated I-131-Hippuran clearance, resulting in a lower estimated ERPF. This study was performed to establish the maximum allowable radiochemical impurity of free I-131-iodide in I-131-Hippuran preparations for ERPF measurements in continuous clearance studies. A known amount of I-123-iodide was added to the (I-131-iodide-free) I-131-Hippuran solution used for continuous infusion clearance studies in nine patients. I-123-iodide activity was used because it can be counted separately from (131)-I-Hippuran in the infusion solutions and plasma samples while it behaves exactly like I-131-iodide, so that the results obtained with I-123-iodide can be extrapolated to I-131-iodide. After performing the clearance studies, the ERPF was calculated firstly with I-131-Hippuran activity only (=true ERPF) and secondly including the free radioactive iodide activity (=false ERPF) in the clearance formula, As expected, if free I-131-iodide is present in the infusion solution, its concentration in plasma will be highest at the end of the clearance study. The I-131-iodide concentration in plasma relative to the I-131-Hippuran concentration will be higher in patients with high ERPF values. I-131-iodide in the infusion solution causes a fall in the ERPF as measured by the continuous infusion technique: 0.5%, 1% and 2% of free I-131-iodide in the infusion solution result in a reduction in ERPF of about 1.5%, 3.5% and 7% respectively after 1.5 h and of 3.5%, 6.5% and 13% respectively after 5.5 h if ERPF is high. It is concluded that a maximum of 0.5% of free I-131-iodide in I-131-Hippuran preparations is permissible if ERPF is to be measured with an error of less than 5%