Pharmacokinetic interactions of enrofloxacin during absorption from the gastrointestinal tract in...

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Association of calpain-10 gene polymorphism and posttransplant diabetes mellitus in kidney transplant patients medicated with tacrolimus Mateusz Kurzawski 1 , Krzysztof Dziewanowski 2 , Karolina Kêdzierska 3 , Wanda Górnik 1 , Marek DroŸdzik 1 New-onset, posttransplant diabetes mellitus (PTDM) has a high incidence after kidney transplantation in patients medicated with tacrolimus, and may ad- versely affect the patient and graft survival. The pa- thophysiology of PTDM closely mimics that of type II diabetes mellitus (T2DM). One of possible genetic factors predisposing to PTDM might be polymor- phism in calpain-10 gene (CAPN10), previously asso- ciated with increased risk of T2DM in general popula- tion. Therefore, the present study was aimed at evaluation of CAPN10 gene polymorphisms in PTDM in kidney transplant patients medicated with tacrolimus. A total of 214 nondiabetic kidney trans- plant patients medicated with tacrolimus (56 patients with PTDM and 158 patients without PTDM were genotyped for the presence of CAPN10 gene variants (SNP-43: rs3792267:G>A, SNP-19: rs3842570 ins/del and SNP-63: rs5030952:C>T) using PCR-based as- says. Frequency of SNP-63 minor allele was slightly increased in PTDM patients (P = 0.056), and an asso- ciation of SNP-63 heterozygosity and the risk of PTDM (odds ratios (OR) = 2.45, P = 0.023) was ob- served. An increased odds for PTDM development in patients carrying 1-1-2 haplotype (rs3792267:G- rs3842570:ins-rs5030952:T) compared to noncarriers was also noted (OR = 2.35, P = 0.026). Patients’ higher body mass index and SNP-63 minor T allele carrier status were identified as independent PTDM risk fac- tors, confirmed by multivariate regression analysis. This is the first study of CAPN10 polymorphism in rela- tion to PTDM risk. However, the application of SNP-63 (rs5030952:C>T) as a marker of PTDM should be verified by further independent studies. Pharmacokinetic interactions of enrofloxacin during absorption from the gastrointestinal tract in turkeys W³odzimierz Markiewicz 1 , Tomasz Maœlanka 1 , Piotr Jakubowski 1 , Tomasz Grabowski 2 , Justyna Pawêska 1 , Ma³gorzata Siemianowska 1 , Jerzy Jaroszewski 1 Pharmakokinetic interaction of fluoroquinolones dur- ing absorption from the gastrointestinal tract in animals are not well known. Therefore, the aim of the present study was to determine the influence of food and cal- cium with magnesium on bioavailability of enrofloxa- cin from the gastrointestinal tract of 4-weeks old tur- keys. Enrofloxacin (10 mg/kg b.w.) was administered as follow: Group I (n = 8) – intravenously, Group II (n = 8) – per os with food, Group III (n = 8) – per os without food, Group IV (n = 8) – per os with calcium (14 mg/kg b.w.) and magnesium (0.38 mg/kg b.w.). Blood samples were collected before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 i 24 h after drug administra- tion (in Group I, additionaly at 5, 15 i 45 min), centri- 87 XVII International Congress of the Polish Pharmacological Society

Transcript of Pharmacokinetic interactions of enrofloxacin during absorption from the gastrointestinal tract in...

Page 1: Pharmacokinetic interactions of enrofloxacin during absorption from the gastrointestinal tract in turkeys

Association of calpain-10 gene polymorphism

and posttransplant diabetes mellitus in kidney transplant patients

medicated with tacrolimus

Mateusz Kurzawski1, Krzysztof Dziewanowski2, Karolina Kêdzierska3, Wanda Górnik1,

Marek DroŸdzik1

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New-onset, posttransplant diabetes mellitus (PTDM)

has a high incidence after kidney transplantation in

patients medicated with tacrolimus, and may ad-

versely affect the patient and graft survival. The pa-

thophysiology of PTDM closely mimics that of type

II diabetes mellitus (T2DM). One of possible genetic

factors predisposing to PTDM might be polymor-

phism in calpain-10 gene (CAPN10), previously asso-

ciated with increased risk of T2DM in general popula-

tion. Therefore, the present study was aimed at

evaluation of CAPN10 gene polymorphisms in

PTDM in kidney transplant patients medicated with

tacrolimus. A total of 214 nondiabetic kidney trans-

plant patients medicated with tacrolimus (56 patients

with PTDM and 158 patients without PTDM were

genotyped for the presence of CAPN10 gene variants

(SNP-43: rs3792267:G>A, SNP-19: rs3842570 ins/del

and SNP-63: rs5030952:C>T) using PCR-based as-

says. Frequency of SNP-63 minor allele was slightly

increased in PTDM patients (P = 0.056), and an asso-

ciation of SNP-63 heterozygosity and the risk of

PTDM (odds ratios (OR) = 2.45, P = 0.023) was ob-

served. An increased odds for PTDM development in

patients carrying 1-1-2 haplotype (rs3792267:G-

rs3842570:ins-rs5030952:T) compared to noncarriers

was also noted (OR = 2.35, P = 0.026). Patients’ higher

body mass index and SNP-63 minor T allele carrier

status were identified as independent PTDM risk fac-

tors, confirmed by multivariate regression analysis.

This is the first study of CAPN10 polymorphism in rela-

tion to PTDM risk. However, the application of SNP-63

(rs5030952:C>T) as a marker of PTDM should be

verified by further independent studies.

Pharmacokinetic interactions of enrofloxacin during absorption

from the gastrointestinal tract in turkeys

W³odzimierz Markiewicz1, Tomasz Maœlanka1, Piotr Jakubowski1, Tomasz Grabowski2,

Justyna Pawêska1, Ma³gorzata Siemianowska1, Jerzy Jaroszewski1

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Pharmakokinetic interaction of fluoroquinolones dur-

ing absorption from the gastrointestinal tract in animals

are not well known. Therefore, the aim of the present

study was to determine the influence of food and cal-

cium with magnesium on bioavailability of enrofloxa-

cin from the gastrointestinal tract of 4-weeks old tur-

keys. Enrofloxacin (10 mg/kg b.w.) was administered

as follow: Group I (n = 8) – intravenously, Group II (n

= 8) – per os with food, Group III (n = 8) – per os

without food, Group IV (n = 8) – per os with calcium

(14 mg/kg b.w.) and magnesium (0.38 mg/kg b.w.).

Blood samples were collected before and 0.5, 1, 1.5,

2, 2.5, 3, 4, 5, 6, 8, 10, 12 i 24 h after drug administra-

tion (in Group I, additionaly at 5, 15 i 45 min), centri-

������������� �� ����� ����� ��� ���� 87

XVII��

International Congress of the Polish Pharmacological Society������ ����������

Page 2: Pharmacokinetic interactions of enrofloxacin during absorption from the gastrointestinal tract in turkeys

fuged and plasma was stored at –30°C until high per-

formacne liquid chromatography determination. Stati-

stical analysis was performed using t-Student test and

pharmacokinetic parameters were calculated using non-

compartmental model (WinNonlin 5.0.1 Professional).

Enrofloxacin bioavailability after treatment with food

was about 51% lower (p < 0.05) as compared to that

found after intravenous administration. In fasted animals,

bioavailability was very good and almost complete, while

after co-administraion with calcium and magnesium,

absolute bioavailability was reduced by 32% (p < 0.05).

Some pharmacokinetic parameters in all experi-

mental groups are presented in table (see above).

The results obtained indicate, that food and ions of

calcium and magnesium significantly reduced absorp-

tion of enrofloxacin from the gastrointestinal tract in

turkeys. Therefore, for effective treatment, their co-

administration should be avoided.

Influence of morin-5’-sulfonic acid sodium salt (NaMSA)

on cyclophosphamide-induced changes in oxido-redox status

in rat liver

Anna Merwid-L¹d1, Ma³gorzata Trocha1, Tomasz Sozañski1, Jan Magdalan1, Ewa Chlebda1,

Dorota Ksi¹dzyna1, Ma³gorzata Pieœniewska1, Lidia Fereniec-Go³êbiewska1, Maria

Kopacz2, Anna KuŸniar2, Dorota Nowak2, Adam Szel¹g1

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Background: Cyclophosphamide (CPX) is an anti-

cancer drug with strong immunosuppressive proper-

ties what makes this drug useful in the treatment of

some autoimmune diseases. The long-term use of

CPX is limited by its adverse effects which, at least

partly, are connected to the induction of oxidative

stress in tissues. Flavonoids are potent antioxidans

and may prevent from some adverse effects induced

by CPX.

Aim: The aim was to evaluate effect of morin-5’-

sulfonic acid sodium salt (NaMSA) – a water-soluble de-

rivative of natural morin on oxido-redox status in rat liver.

Materials and Methods: Experiment was carried

out on Wistar rats of both sexes (203.9 g ± 18.6 g) ar-

88 ������������� �� ����� ����� ��� ����

Parameter Treatment

Intravenous injection Per os + fed Per os + fasted Per os + Ca and Mg

t������

(h) 5.08 ± 0.57 15.23 ± 3.71* 5.76 ± 0.76 4.10 ± 0.21

t��

(h) 0.08 ± 0.0 5.06 ± 1.09* 2.19 ± 0.34* 1.65 ± 0.27*

C��

(μg/ml) 2.60 ± 0.39 0.44 ± 0.03* 1.87 ± 0.22 1.02 ± 0.06*

AUC�� �

(mg/l h) 10.75 ± 1.72 5.29 ± 0.46* 13.09 ± 1.37 7.27 ± 0.38*

Cl����

(l/h kg) 1.12 ± 0.22 1.39 ± 0.17 0.80 ± 0.10 1.38 ± 0.07

MRT�� �

(h) 6.04 ± 0.46 23.53 ± 5.30* 7.67 ± 0.57 6.87 ± 0.23

F (%) – 49.14 ± 4.30 99.0 ± 3.0 67.58 ± 6.30

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