ArticleClinical pharmacokinetics2022
Population Pharmacokinetics of Intra-articular and Intravenous Administration of Tranexamic Acid in Patients Undergoing Total Knee Replacement.
Article in Clinical pharmacokinetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed, 1 synthesis or guideline pooled it, 4 citations in OpenAlex.
- Pharmacological interventions for the prevention of bleeding in people undergoing elective hip or knee surgery: a systematic review and network meta-analysis.The Cochrane database of systematic reviews · 2024Pooled it
- Is Combined Tranexamic Acid Administration Superior to Single-Route Protocols in Primary Total Knee Arthroplasty? A Prospective Cohort Study.Journal of clinical medicine · 2026Article
- Tranexamic Acid in Combination With Vancomycin or Gentamicin Has a Synergistic Effect Against Staphylococci.Frontiers in microbiology · 2022Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTranexamic acid (TXA), an antifibrinolytic drug, is usually administered intravenously; however, intra-articular administration has recently been proven to be as effective as intravenous administration. Limited information regarding the pharmacokinetics (PK) of TXA after intra-articular administration has been reported.
aimsThe aim of this study was to develop a population PK model of TXA administered as a single intra-articular dose and as two intravenous doses, and to study the sources of interindividual variability (IIV) in the PK processes of TXA. The developed model was used to simulate PK profiles of TXA at different dosage regimens and in patients with renal impairment.
methodsPatients who underwent primary unilateral total knee replacement (TKR) received 1 g/10 mL (concentration of 100 mg/mL) of TXA applied directly to the surgical field before wound closure, or 2 g (two doses of 1 g) of intravenous TXA. A population PK model was developed using a nonlinear mixed-effects approach and sources of IIV, such as sex, age, body weight, height, body mass index (BMI), preoperative haemoglobin, preoperative haematocrit, and creatinine clearance.
resultsTwenty-four patients were included, 12 in each group. Twenty patients were female, mean age (standard deviation) was 73.7 years (5.6). The disposition of TXA was best described as a two-compartment model with clearance dependent on creatinine clearance. Bootstrap results indicated that the model was stable and robust. The estimated bioavailability for intra-articular administration was 81%. Simulations indicated that 100% of patients would have plasma concentrations associated with partial fibrinolysis at 8 h post-administration with the dosages and routes of administration used in the present study. Intra-articular administration would produce complete inhibition of fibrinolysis in only 12% of patients compared with 72.5% with intravenous administration. No adverse events were reported.
conclusionsThis population PK model demonstrated that a single dose of high-concentration, low-volume intra-articular TXA can achieve antifibrinolytic plasma concentrations of the drug for 8 h, providing both local and systemic effects in patients undergoing TKR. TXA administration to the surgical field could be an alternative to the intravenous; route for patients undergoing TKR; however, clinical studies are needed to assess the toxic local effects of TXA.
trial registrationSpanish Clinical Studies Registry Number: 2017-004059-22. Date of registration: 12 April 2018.
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