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Qian Zhang,
Claire Bal-dit-Sollier,
Ludovic Drouet,
Guy Simoneau,
Jean-Claude Alvarez,
Sandrine Pruvot,
Romain Aubourg,
Natacha Berge, Jean-Francois Bergmann,
Stéphane Mouly,
Isabelle Mahé
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ABSTRACT: We investigated whether acetaminophen, given at 2 g/day and 3 g/day might potentiate the anticoagulant effect of warfarin.
Forty-five patients on stable warfarin therapy, enrolled in this prospective, randomized, parallel (three arms), placebo-controlled study, received a 10-day regimen of acetaminophen (2 g/day or 3 g/day) or placebo.
The mean maximal INR increase was 0.70 ± 0.49 and 0.67 ± 0.62 in patients receiving acetaminophen at 2 g/day and 3 g/day, respectively (P=0.01 for the respective comparisons versus placebo). The INR increase became significant on day 3 and was independently and significantly predicted by a maximal decrease in factor II (R(2)=0.36, P<0.0001), factor VII (R (2)=0.46, P<0.0001) and a maximal increase in acetaminophen plasma concentrations (R(2)=0.563, P<0.0001).
Acetaminophen, at 2 g/day or 3 g/day, enhanced the anticoagulant effect of warfarin in stable patients, thus requiring close INR monitoring in the clinical setting.
European Journal of Clinical Pharmacology 03/2011; 67(3):309-14. · 2.85 Impact Factor
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ABSTRACT: To investigate whether an interaction exists between amoxicillin/clavulanic acid (amoxiclav) and warfarin in patients treated with stable oral anticoagulant therapy.
In a double-blind, cross-over, placebo-controlled study, 12 patients on stable warfarin therapy, received a 7 day amoxiclav regimen or placebo.
The mean maximum increase in INR observed was 0.22 ± 0.3 with amoxiclav vs. 0.24 ± 0.6 with placebo (P=0.94). The day 7-day 1 factor II, R(-) and S(-) warfarin plasma concentrations were similar during the amoxiclav and placebo study periods (P=0.81, P=0.45, P=0.75, respectively).
Amoxiclav did not modify anticoagulation in patients treated with stable warfarin therapy and without infection.
British Journal of Clinical Pharmacology 02/2011; 71(2):232-6. · 2.96 Impact Factor
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ABSTRACT: We aimed to describe the pharmacokinetic interaction between phenytoin, a potent CYP3A4 and P-glycoprotein (P-gp) (ABCB1) inducer, and gefitinib, a CYP3A4, CYP2D6 and P-gp substrate.
An open-label, randomized, two-phase crossover study was conducted. Eighteen healthy male volunteers (nine homozygous CC and nine homozygous TT as determined by their ABCB1 C3435T polymorphism in exon 26) received a single oral dose of 250 mg gefitinib alone or after 5 days treatment with phenytoin (5 mg kg(-1) daily). Gefitinib plasma concentrations were determined by high-performance liquid chromatography. Hepatic CYP3A4 activity was evaluated by the (14)C-erythromycin breath test (ERMBT) and the ABCB1 and CYP2D6 genetic polymorphisms were determined by the TaqMan allelic discrimination assay and long polymerase chain reaction, respectively.
Following treatment with phenytoin, mean gefitinib C(max) and AUC(0-infinity) decreased by 26 +/- 44% [95% confidence interval (CI) for the difference 5-48%, P= 0.005] and 47 +/- 26% (95% CI for the difference 34-60%, P= 0.001), respectively, and apparent oral clearance increased by 126 +/- 93% (95% CI for the difference 80-172%, P= 0.004). Concomitantly, phenytoin increased the mean ERMBT by 91 +/- 44% (95% CI 75-105%, P < 0.001) from baseline, but the extent of liver CYP3A4 induction was not correlated to the extent of interaction. Furthermore, this interaction was independent of ABCB1 genetic polymorphism. The CYP2D6 genotype was slightly but significantly related to gefitinib clearance (P= 0.04) during the control phase.
The significant interaction between gefitinib and phenytoin was not correlated with the erythromycin breath test and was independent of ABCB1 polymorphism, but may involve presystemic CYP3A-mediated intestinal first-pass.
British Journal of Clinical Pharmacology 08/2009; 68(2):226-37. · 2.96 Impact Factor
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Pierre Sellier,
Philippe Clevenbergh,
Marie-Christine Mazeron,
Dominique Cazals-Hatem,
John Evans,
Jeanine Cervoni,
Esma Badsi,
Marc Bendenoun,
Myriam Diemer,
Valerie Vincent,
Charles Caulin, Jean-Francois Bergmann
Scandinavian Journal of Infectious Diseases 02/2004; 36(6-7):533-5. · 1.72 Impact Factor
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ABSTRACT: Venous thromboembolism occurs frequently in both medical and surgical units. Although we possess the therapeutic means to prevent this condition, the question is how to assess the benefit induced by a treatment in relation to the haemorrhagic risk? The primary evaluation criteria and the evaluation method must be correctly chosen. While phlebography is the reference method for diagnosing deep venous thrombosis, the limitations associated with this method have led to the promotion of other diagnostic techniques, and clinical criteria or composite criteria are increasingly used. These different approaches--with their respective advantages and limitations--will be developed.
Thérapie 58(4):327-31. · 0.30 Impact Factor
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ABSTRACT: Venous thromboembolism occurs frequently in both medical and surgical units. Although we possess the therapeutic means to prevent this condition, the question is how to assess the benefit induced by a treatment in relation to the haemorrhagic risk? The primary evaluation criteria and the evaluation method must be correctly chosen. While phlebography is the reference method for diagnosing deep venous thrombosis, the limitations associated with this method have led to the promotion of other diagnostic techniques, and clinical criteria or composite criteria are increasingly used. These different approaches – with their respective advantages and limitations – will be developed. La pathologie veineuse thromboembolique est fréquente, que ce soit en médecine ou en chirurgie. Nous avons à notre disposition des moyens thérapeutiques pour prévenir ce risque thromboembolique mais la question se pose de savoir comment évaluer le bénéfice induit par un traitement par rapport au risque hémorragique encouru ? Cela passe par le choix du critère principal d'évaluation et d'une méthode diagnostique de référence. Or, en matière de prévention thromboembolique veineuse, la phlébographie est historiquement la méthode de référence pour détecter les thromboses veineuses profondes mais elle comporte des limites qui ont conduit à proposer d'autres méthodes diagnostiques ou l'adoption de critères plus cliniques ou encore des critères composites. Ces différentes approches seront développées, avec leurs propres avantages et leurs limites.
http://dx.doi.org/10.2515/therapie:2003050.
