Pharmacokinetics of tranexamic acid after intravenous administration to normal volunteers

Eriksson, Olle; Kjellman, H; Pilbrant, A; Schannong, M

doi:10.1007/bf00558210

Cited by 132 publications

(74 citation statements)

References 5 publications

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“…This analysis yielded a plasma concentration of approximately 0.2 mg/l TA, roughly 16 hours after the last dose of drug. This is similar to levels observed at this time after administration of a therapeutic dose of TA in humans (Eriksson et al, 1974;Pilbrant et al, 1981).…”

Section: Resultssupporting

confidence: 87%

“…Thus, one mechanism whereby TA treatment could reduce ANIT-induced liver injury is by inhibiting plasmin-mediated fibrinolysis, thereby stabilizing hepatic fibrin deposits. Our results indicate that plasma TA levels in TA-treated mice sufficiently prolonged clot lysis ex vivo, consistent with inhibition of plasmin, and were similar to those observed in TA-treated humans (Eriksson et al, 1974;Pilbrant et al, 1981). Although TA treatment probably sustained hepatic fibrin deposition in ANIT-treated mice, we were unable to detect a significant increase in hepatic fibrin deposition in ANIT-treated mice given TA.…”

Section: Discussionsupporting

confidence: 80%

“…This dose was selected as approximating the range of TA doses used in previous mouse studies (Hattori et al, 2000;Sullivan et al, 2012b) and was well tolerated by the mice. The dose required in mice is higher than the recommended human dose (4 g per day), because of the rapid elimination of TA in the kidney by glomerular filtration (Eriksson et al, 1974). For Experiment 2, mice were fed a control diet or ANIT diet for 4 weeks, and TA or its vehicle were administered only in weeks 3 and 4.…”

Section: Methodsmentioning

confidence: 99%

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The Antifibrinolytic Drug Tranexamic Acid Reduces Liver Injury and Fibrosis in a Mouse Model of Chronic Bile Duct Injury

Joshi

Kopec

Towery

et al. 2014

J Pharmacol Exp Ther

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Hepatic fibrin deposition has been shown to inhibit hepatocellular injury in mice exposed to the bile duct toxicant a-naphthylisothiocyanate (ANIT). Degradation of fibrin clots by fibrinolysis controls the duration and extent of tissue fibrin deposition. Thus, we sought to determine the effect of treatment with the antifibrinolytic drug tranexamic acid (TA) and plasminogen activator inhibitor-1 (PAI-1) deficiency on ANIT-induced liver injury and fibrosis in mice. Plasmin-dependent lysis of fibrin clots was impaired in plasma from mice treated with TA (1200 mg/kg i.p., administered twice daily). Prophylactic TA administration reduced hepatic inflammation and hepatocellular necrosis in mice fed a diet containing 0.025% ANIT for 2 weeks. Hepatic type 1 collagen mRNA expression and deposition increased markedly in livers of mice fed ANIT diet for 4 weeks. To determine whether TA treatment could inhibit this progression of liver fibrosis, mice were fed ANIT diet for 4 weeks and treated with TA for the last 2 weeks. Interestingly, TA treatment largely prevented increased deposition of type 1 collagen in livers of mice fed ANIT diet for 4 weeks. In contrast, biliary hyperplasia/inflammation and liver fibrosis were significantly increased in PAI-1 2/2 mice fed ANIT diet for 4 weeks. Overall, the results indicate that fibrinolytic activity contributes to ANIT diet-induced liver injury and fibrosis in mice. In addition, these proof-of-principle studies suggest the possibility that therapeutic intervention with an antifibrinolytic drug could form a novel strategy to prevent or reduce liver injury and fibrosis in patients with liver disease.

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Section: Resultssupporting

confidence: 87%

Section: Discussionsupporting

confidence: 80%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

The Antifibrinolytic Drug Tranexamic Acid Reduces Liver Injury and Fibrosis in a Mouse Model of Chronic Bile Duct Injury

Joshi

Kopec

Towery

et al. 2014

J Pharmacol Exp Ther

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“…Since TXA has a plasma half-life of 1.9 hours, [28] and our anticipated duration of surgery averaged two hours, a bolus injection of 10 mg/kg weight was chosen as the dosage to…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Tranexamic acid in Reducing Blood Loss During Maxillofacial Trauma Surgery–A Pilot Study

Dakir

Ramalingam

Ebenezer

et al. 2014

JCDR

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“…These authors also thought hemostatic control was better when tranexamic acid was administered before surgery rather than on deflation of the tourniquet and suggested suppression of fibrinolysis from the beginning of the operation may be more effective than only later at the time of peak hyperfibrinolysis [53]. Pharmacokinetic studies [5,13,49,57] indicate a dose of 20 mg/kg tranexamic acid is suitable for TKA. A therapeutic level can be maintained for approximately 8 hours after surgery, and this covers the period of hyperfibrinolysis in cases of increased blood loss [25].…”

Section: Discussionmentioning

confidence: 99%

Tranexamic Acid Reduces Blood Loss and Blood Transfusion after TKA: A Prospective Randomized Controlled Trial

Charoencholvanich

Siriwattanasakul

2011

Clinical Orthopaedics &Amp; Related Research

138

105

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Background TKA may be associated with considerable blood loss, and transfusion carries substantial risk of immunologic reaction and disease transmission. Blood transfusion also involves additional cost, therefore a reduction in its use is important. Several methods reportedly reduce postoperative blood loss and avoid homologous blood transfusion with traditional TKA approaches, but it is unclear these reductions apply to a minimally invasive technique. Questions/purposes We asked whether tranexamic acid administration could reduce blood loss and blood transfusion requirements after TKA.

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Pharmacokinetics of tranexamic acid after intravenous administration to normal volunteers

Cited by 132 publications

References 5 publications

The Antifibrinolytic Drug Tranexamic Acid Reduces Liver Injury and Fibrosis in a Mouse Model of Chronic Bile Duct Injury

The Antifibrinolytic Drug Tranexamic Acid Reduces Liver Injury and Fibrosis in a Mouse Model of Chronic Bile Duct Injury

Efficacy of Tranexamic acid in Reducing Blood Loss During Maxillofacial Trauma Surgery–A Pilot Study

Tranexamic Acid Reduces Blood Loss and Blood Transfusion after TKA: A Prospective Randomized Controlled Trial

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