PHARMACOGENETICS OF METFORMIN

Publikation: Konferencebidrag uden forlag/tidsskriftPosterFormidling

Resumé

Introduction: Genetic polymorphisms in metformin transporters and their impact at the steady state metformin plasma concentrations is evaluated in a large well characterized type 2 diabetes cohort given by South Danish Diabetes Study. SNPs in PMAT, OCT1-2 and MATE 1-2 have been linked to reduced pharmacodynaminc response and large interindividual pharmacokinetic variation. Materials/Patients: South Danish Diabetes Study was designed as a 2 x 2 x 2 factorial prospective, randomized, double-blinded, placebo-controlled, multi-centre study comprising 386 in 8 parallel groups. It was initialized to investigate the optimal pharmacological combination of metformin, rosiglitazon and insulin Asp/NPH in a cohort of type 2 diabetics. One hundred and eighty-six patients were allocated to metformin, and repeated measurements of steady state concentrations were collected. The final results will be adjusted for gender, age, BMI, duration of disease, metformin dose, co-medication, smoking, creatinine clearance, HbA1c-pretreatment and polymorphisms in PMAT, OCT 1-2 and MATE 1-2. Results: The preliminary unadjusted result
for 456 repeated measurements of metformin confirm the large inter-individual variation in steady state metformin concentration:769 ± 649ng/ml (SD), range: 9.7 to 4133ng/ml. In the cohort 369 samples could be genotyped. In the renal transporter OCT2, the A270S genotype frequencies were determined: heterozygous 19%, homozygous 0.5% and wild-type 80.5%, which corresponds well with the databases at NCBI. Conclusion: The preliminary results strengthen the thesis that Danish type 2 diabetics have the same allele frequencies in transporter SNP as healthy Caucasian, and it indeed underscores the enormous interindividual variation in metformin steady state concentration.
OriginalsprogEngelsk
Publikationsdato2010
StatusUdgivet - 2010
Begivenhed16th World Congress of Basic and Clinical Pharmacology, WorldPharma2010 - København, Danmark
Varighed: 17. jul. 201023. jul. 2010

Konference

Konference16th World Congress of Basic and Clinical Pharmacology, WorldPharma2010
LandDanmark
ByKøbenhavn
Periode17/07/201023/07/2010

Fingeraftryk

Pharmacogenetics
Single Nucleotide Polymorphism
Genetic Polymorphisms
Viperidae
Type 2 Diabetes Mellitus
Creatinine
Pharmacokinetics
Smoking
Placebos
Databases
Kidney

Citer dette

Hougaard Christensen, M. M., Andersen, C. B., Damkier, P., Beck-Nielsen, H., & Brøsen, K. (2010). PHARMACOGENETICS OF METFORMIN. Poster session præsenteret på 16th World Congress of Basic and Clinical Pharmacology, WorldPharma2010, København, Danmark.
Hougaard Christensen, Mette Marie ; Andersen, Charlotte Brasch ; Damkier, Per ; Beck-Nielsen, Henning ; Brøsen, Kim. / PHARMACOGENETICS OF METFORMIN. Poster session præsenteret på 16th World Congress of Basic and Clinical Pharmacology, WorldPharma2010, København, Danmark.
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title = "PHARMACOGENETICS OF METFORMIN",
abstract = "Introduction: Genetic polymorphisms in metformin transporters and their impact at the steady state metformin plasma concentrations is evaluated in a large well characterized type 2 diabetes cohort given by South Danish Diabetes Study. SNPs in PMAT, OCT1-2 and MATE 1-2 have been linked to reduced pharmacodynaminc response and large interindividual pharmacokinetic variation. Materials/Patients: South Danish Diabetes Study was designed as a 2 x 2 x 2 factorial prospective, randomized, double-blinded, placebo-controlled, multi-centre study comprising 386 in 8 parallel groups. It was initialized to investigate the optimal pharmacological combination of metformin, rosiglitazon and insulin Asp/NPH in a cohort of type 2 diabetics. One hundred and eighty-six patients were allocated to metformin, and repeated measurements of steady state concentrations were collected. The final results will be adjusted for gender, age, BMI, duration of disease, metformin dose, co-medication, smoking, creatinine clearance, HbA1c-pretreatment and polymorphisms in PMAT, OCT 1-2 and MATE 1-2. Results: The preliminary unadjusted result for 456 repeated measurements of metformin confirm the large inter-individual variation in steady state metformin concentration:769 ± 649ng/ml (SD), range: 9.7 to 4133ng/ml. In the cohort 369 samples could be genotyped. In the renal transporter OCT2, the A270S genotype frequencies were determined: heterozygous 19{\%}, homozygous 0.5{\%} and wild-type 80.5{\%}, which corresponds well with the databases at NCBI. Conclusion: The preliminary results strengthen the thesis that Danish type 2 diabetics have the same allele frequencies in transporter SNP as healthy Caucasian, and it indeed underscores the enormous interindividual variation in metformin steady state concentration.",
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Hougaard Christensen, MM, Andersen, CB, Damkier, P, Beck-Nielsen, H & Brøsen, K 2010, 'PHARMACOGENETICS OF METFORMIN' 16th World Congress of Basic and Clinical Pharmacology, WorldPharma2010, København, Danmark, 17/07/2010 - 23/07/2010, .

PHARMACOGENETICS OF METFORMIN. / Hougaard Christensen, Mette Marie; Andersen, Charlotte Brasch; Damkier, Per; Beck-Nielsen, Henning; Brøsen, Kim.

2010. Poster session præsenteret på 16th World Congress of Basic and Clinical Pharmacology, WorldPharma2010, København, Danmark.

Publikation: Konferencebidrag uden forlag/tidsskriftPosterFormidling

TY - CONF

T1 - PHARMACOGENETICS OF METFORMIN

AU - Hougaard Christensen, Mette Marie

AU - Andersen, Charlotte Brasch

AU - Damkier, Per

AU - Beck-Nielsen, Henning

AU - Brøsen, Kim

PY - 2010

Y1 - 2010

N2 - Introduction: Genetic polymorphisms in metformin transporters and their impact at the steady state metformin plasma concentrations is evaluated in a large well characterized type 2 diabetes cohort given by South Danish Diabetes Study. SNPs in PMAT, OCT1-2 and MATE 1-2 have been linked to reduced pharmacodynaminc response and large interindividual pharmacokinetic variation. Materials/Patients: South Danish Diabetes Study was designed as a 2 x 2 x 2 factorial prospective, randomized, double-blinded, placebo-controlled, multi-centre study comprising 386 in 8 parallel groups. It was initialized to investigate the optimal pharmacological combination of metformin, rosiglitazon and insulin Asp/NPH in a cohort of type 2 diabetics. One hundred and eighty-six patients were allocated to metformin, and repeated measurements of steady state concentrations were collected. The final results will be adjusted for gender, age, BMI, duration of disease, metformin dose, co-medication, smoking, creatinine clearance, HbA1c-pretreatment and polymorphisms in PMAT, OCT 1-2 and MATE 1-2. Results: The preliminary unadjusted result for 456 repeated measurements of metformin confirm the large inter-individual variation in steady state metformin concentration:769 ± 649ng/ml (SD), range: 9.7 to 4133ng/ml. In the cohort 369 samples could be genotyped. In the renal transporter OCT2, the A270S genotype frequencies were determined: heterozygous 19%, homozygous 0.5% and wild-type 80.5%, which corresponds well with the databases at NCBI. Conclusion: The preliminary results strengthen the thesis that Danish type 2 diabetics have the same allele frequencies in transporter SNP as healthy Caucasian, and it indeed underscores the enormous interindividual variation in metformin steady state concentration.

AB - Introduction: Genetic polymorphisms in metformin transporters and their impact at the steady state metformin plasma concentrations is evaluated in a large well characterized type 2 diabetes cohort given by South Danish Diabetes Study. SNPs in PMAT, OCT1-2 and MATE 1-2 have been linked to reduced pharmacodynaminc response and large interindividual pharmacokinetic variation. Materials/Patients: South Danish Diabetes Study was designed as a 2 x 2 x 2 factorial prospective, randomized, double-blinded, placebo-controlled, multi-centre study comprising 386 in 8 parallel groups. It was initialized to investigate the optimal pharmacological combination of metformin, rosiglitazon and insulin Asp/NPH in a cohort of type 2 diabetics. One hundred and eighty-six patients were allocated to metformin, and repeated measurements of steady state concentrations were collected. The final results will be adjusted for gender, age, BMI, duration of disease, metformin dose, co-medication, smoking, creatinine clearance, HbA1c-pretreatment and polymorphisms in PMAT, OCT 1-2 and MATE 1-2. Results: The preliminary unadjusted result for 456 repeated measurements of metformin confirm the large inter-individual variation in steady state metformin concentration:769 ± 649ng/ml (SD), range: 9.7 to 4133ng/ml. In the cohort 369 samples could be genotyped. In the renal transporter OCT2, the A270S genotype frequencies were determined: heterozygous 19%, homozygous 0.5% and wild-type 80.5%, which corresponds well with the databases at NCBI. Conclusion: The preliminary results strengthen the thesis that Danish type 2 diabetics have the same allele frequencies in transporter SNP as healthy Caucasian, and it indeed underscores the enormous interindividual variation in metformin steady state concentration.

M3 - Poster

ER -

Hougaard Christensen MM, Andersen CB, Damkier P, Beck-Nielsen H, Brøsen K. PHARMACOGENETICS OF METFORMIN. 2010. Poster session præsenteret på 16th World Congress of Basic and Clinical Pharmacology, WorldPharma2010, København, Danmark.