In vitro effect of beta-lactam antibiotics and N-methyl-tetrazolethiol on microsomal vitamin K epoxide reductase in rats.

Kawamoto, Keiko; Touchi, Akira; Sugeno, Koichi; Matsubara, Takashi

doi:10.1254/jjp.47.169

Cited by 12 publications

(5 citation statements)

References 39 publications

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“…the N-methyl-thio-tetrazole (NMTT) group and beta-lactam antibiotics, have been reported to interact with warfarin [1,2]. Amoxicillin/clavulanic acid (amoxiclav), a member of the penicillin class, also has been suggested to potentiate the effects of warfarin [3].…”

Section: Introductionmentioning

confidence: 99%

Amoxicillin/clavulanic acid‐warfarin drug interaction: a randomized controlled trial

Zhang

Simoneau

Verstuyft

et al. 2011

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Increased INR was previously observed in patients treated with warfarin and amoxicillin/clavulanic acid (amoxiclav) combination. To date, no prospective study has yet evaluated the effect of amoxiclav on INR in patients on warfarin therapy and consequently, there are no clear-cut conclusions or clear recommendations for clinicians. WHAT THIS PAPER ADDS• We provided the first systematic prospective evaluation of the interaction between amoxiclav and warfarin and found that amoxiclav did not modify INR in patients treated with stable warfarin therapy in the absence of any infectious or inflammatory syndrome, suggesting that the previously observed INR increase in these patients may not be attributable to a drug-drug interaction. AIMSTo investigate whether an interaction exists between amoxicillin/clavulanic acid (amoxiclav) and warfarin in patients treated with stable oral anticoagulant therapy. METHODSIn a double-blind, cross-over, placebo-controlled study, 12 patients on stable warfarin therapy, received a 7 day amoxiclav regimen or placebo. RESULTSThe mean maximum increase in INR observed was 0.22 Ϯ 0.3 with amoxiclav vs. 0.24 Ϯ 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). CONCLUSIONAmoxiclav did not modify anticoagulation in patients treated with stable warfarin therapy and without infection.

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Section: Introductionmentioning

confidence: 99%

Amoxicillin/clavulanic acid‐warfarin drug interaction: a randomized controlled trial

Zhang

Simoneau

Verstuyft

et al. 2011

Brit J Clinical Pharma

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“… 4 Some reports advocated that the interaction is likely to occur following antibiotics that contain the functional group N‐methyl tetrazole thiol (NMTT), thiadiazole thiol (TDT), or methyl thiadiazole thiol (MTDT), which directly inhibits vitamin K epoxide reductase, or vitamin K epoxide reductase (VKOR) in the intestinal flora, which leads prolongation of anticoagulant effects by the reduction for vitamin K production in the intestine. 5 , 6 , 7 , 8 , 9 , 10 , 11 On the contrary, when we conducted a survey using real‐world data, we reported that it was likely to difficult to solely attribute these causes to the NMTT side chain because of several limitations including sample size, etc. 12 In our case, the meropenem we coadministered with warfarin in our patient population does not have above mentioned functional groups.…”

Section: Discussionmentioning

confidence: 98%

A super‐geriatric patient with gastrostomy underwent life‐threatening prothrombin time‐international normalized ratio prolongation by warfarin following fasting and antibiotic therapy

Saeki,

Watanabe,

Momo

et al. 2023

Clinical Case Reports

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Key Clinical MessageA 97‐year‐old woman with gastrostomy had a drastic enhancement for PT‐INR after starting antibiotic therapy. Possible causes include (1) vitamin K deficiency due to fasting and (2) a combination of warfarin and antibiotics.AbstractGeriatric and Asian‐descent patients are more sensitive to the effects of warfarin, a key anticoagulant drug. In this report, we present a 97‐year‐old bedridden woman being treated with warfarin for cardiogenic cerebral infarction and femoral neck replacement as part of in‐home medical care with a gastrostomy and was admitted to our hospital after developing pneumonia. We discontinued warfarin and started antibiotics, and her pneumonia‐related symptoms improved. Eleven days after restarting warfarin, the patient's PT‐INR surpassed the upper limit for measurement (over 10). We considered the mechanism might be triggered by (1) fasting, low nutrition status; and (2) antibiotics secondary to risk factors such as gastrostomy and being a super‐geriatric woman. We recommend careful monitoring of PT‐INR in patients treated with warfarin and antibiotics, especially in the setting of gastrostomy or older persons.

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“…Moxalactam has not been found to affect the levels of vitamin K-dependent clotting factors II, VII, IX, and X or vitamin K-independent clotting factors V, VIII, and I. Moxalactarn, and 27 out of the 33 additional beta-Iactarn antibiotics investigated, were found to suppress ADP-induced platelet aggregation at high concentrations in vitro. Many newer therapeutic agents and older broad-spectrum antibiotics induce hypoprothrombinemia with or without bleeding complications in weaker patients due to the suppression of intestinal bacteria that synthesize vitamin K (40)(41)(42) and in the lowering of liver microsomal vitamin K epoxide reductase activity and thus causing hypoprothrombinemia even in the presence of vitamin K sufficiency. Moreover vitamin K administration could normalize the blood coagulation parameters in hypoprothrombinemic rats caused by antibiotic treatment, but without recovery of the reduced epoxide reductase activity (41,42).…”

Section: Discussionmentioning

confidence: 99%

Anticoagulant-induced changes on antibiotic concentrations in the serum and bones

Kotsiou

Diamanti

Potamianou

et al. 2008

Eur. J. Drug Metabol. Pharmacokinet.

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The aim of this study was to determine whether the co-administration of acenocoumarin as anticoagulant and certain quinolones, i.e., cefapirin, pefloxacin and ciprofloxacin increased the levels of the given antibiotics and whether this resulted in a prolongation of prothrombin time. Seventy male albino Wistar rats aged 8-10 weeks and weighed 170 +/- 14 g were used and divided into seven groups (I, II, III, IV, V, VI, VII: n=10). The rats in group I received cefapirin via 1 g/kg/8h im injection. Group II received cefapirin via of 1 g/kg/8h im injection and 0.1 mg/kg/24h p.o. acenocoumarin. Group III received ciprofloxacin 0.18 mg/kg/24h im. Group IV received ciprofloxacin 0.18 mg/kg/24h im and 0.1 mg/kg/24h p.o. acenocoumarin. Group V received 10 mg/kg/24h pefloxacin im. Group VI received 10 mg/kg/24h pefloxacin im and 0.1 mg/kg/24h p.o. acenocoumarin while Group VII received only acenocoumarin 0.1 mg/kg/24h p.o. Drug administration was performed over a total of 5 doses in order to obtain steady state concentrations in the plasma and tissues. The animals were sacrificed by decapitation 2 h after the last antibiotic administration. Prothrombin time and antibiotic concentrations in the serum, femur and mandible were assessed. In the study, all the antibiotics were found to prolong prothrombine time following acenocoumarin administration. In addition, perfloxacin and ciproflaxin concentrations were increased in the serum and mandible after acenocoumarin treatment. Cepafirin levels remained unaffected after the administration of this anticoagulant. In conclusion, anticoagulant and quinolone co-administration led to significant pharmacokinetic interactions. Thus particular attention should be paid in the case of these drugs being used in combination in clinical practice.

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In vitro effect of beta-lactam antibiotics and N-methyl-tetrazolethiol on microsomal vitamin K epoxide reductase in rats.

Cited by 12 publications

References 39 publications

Amoxicillin/clavulanic acid‐warfarin drug interaction: a randomized controlled trial

Amoxicillin/clavulanic acid‐warfarin drug interaction: a randomized controlled trial

A super‐geriatric patient with gastrostomy underwent life‐threatening prothrombin time‐international normalized ratio prolongation by warfarin following fasting and antibiotic therapy

Anticoagulant-induced changes on antibiotic concentrations in the serum and bones

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