Obesity is Associated with a Slower Response to Initial Phenprocoumon Therapy Whereas CYP2C9 Genotypes Are Not

Overview

Journal Eur J Clin Pharmacol

Specialty Pharmacology

Date 2006 Jul 19

PMID 16847664

Citations 8

Authors

Cordula Meyer Zu Schwabedissen

Vera Mevissen

Fabian Schmitz

Seth Woodruff

Georg Langebartels

Thomas Rau

Klaus Zerres

Rainer Hoffmann

Jan R Ortlepp

Affiliations

Soon will be listed here.

Abstract

Background: Initiation of phenprocoumon therapy is associated with a variable individual response. The CYP2C9 genotype has been shown to influence the response to warfarin therapy, but such an effect on phenprocoumon therapy remains uncertain.

Method: Two hundred sixty hospital patients started on phenprocoumon were recruited for this study. Body mass index (BMI), waist and hip circumference, dietary habits, comorbidity, and comedication were initially assessed. A 5' exonuclease assay (TaqManR) was used to analyze the presence of five polymorphisms of the CYP2C9 gene in each of the study patients. Study endpoints included the time necessary to achieve the international normalized ratio (INR) target (INR >2) and the total drug amount required to attain target INR. For 250 of 260 patients, the subsequent required daily maintenance dose of phenprocoumon was also recorded.

Results: Both the necessary time and total dose required to attain target INR correlated significantly with BMI. The leaner the patient, the shorter the required time interval [BMI <22 (n=31), 5.48+/-2.49 days; BMI 22-25 (n=70), 6.09+/-2.40; BMI 25-30 (n=113), 6.76+/-3.61; BMI >30 (n=46), 8.50+/-5.75; p=0.001] and the lower the required dosage until the therapeutic range was achieved [BMI <22 (n=31), 23.8+/-12.1 mg; BMI 22-25 (n=70), 25.9+/-11.4 mg; BMI 25-30 (n=113), 29.6+/-25.2; BMI >30 (n=46), 35.8+/-19.7; p=0.027]. Overweight and waist circumference as a surrogate marker for abdominal fat were also associated significantly with these two parameters. Moreover, obesity was associated with a lower body-weight-adjusted maintenance dosage. All CYP2C9 genotypes that were tested failed to reveal an association with individual response variability.

Conclusion: Patient obesity appears to directly correspond to the amount of phenprocoumon required during initiation of therapy. The CYP2C9 genotype was not shown to influence the necessary therapeutic dosage.

Citing Articles

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Wen X, Wang S, Taveira T, Akhlaghi F PLoS One. 2021; 16(9):e0251665.

PMID: 34525124 PMC: 8443040. DOI: 10.1371/journal.pone.0251665.

Impact of Body Mass Index and Genetics on Warfarin Major Bleeding Outcomes in a Community Setting.

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Comparison of initial warfarin response in obese patients versus non-obese patients.

Wallace J, Reaves A, Tolley E, Oliphant C, Hutchison L, Alabdan N J Thromb Thrombolysis. 2012; 36(1):96-101.

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Drug interactions with phenprocoumon and the risk of serious haemorrhage: a nested case-control study in a large population-based German database.

Jobski K, Behr S, Garbe E Eur J Clin Pharmacol. 2011; 67(9):941-51.

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