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Population Pharmacokinetics of Intra-articular and Intravenous Administration of Tranexamic Acid in Patients Undergoing Total Knee Replacement
- Source :
- CLINICAL PHARMACOKINETICS, r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, instname
- Publication Year :
- 2022
- Publisher :
- ADIS INT LTD, 2022.
-
Abstract
- Background Tranexamic 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. Aims The 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. Methods Patients 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. Results Twenty-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. Conclusions This 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.
- Subjects :
- hypotension
absorption rate constant
limit of quantitation
phase 1 clinical trial
diarrhea
phlebitis
population pharmacokinetic model
creatinine clearance
anxiety disorder
antibiotic agent
femoral nerve paraesthesia
fever
analytic method
clinical article
peripheral volume of distribution
drug dose regimen
creatinine
aged
confusion
female
body height
hyperesthesia
descriptive research
cardiovascular risk
pharmacokinetic parameters
hematocrit
adverse drug reaction
parallel design
antifibrinolytic agent
Caucasian
tranexamic acid
Article
paresthesia
body weight
open study
male
demographics
operative blood loss
case report
controlled study
human
intermethod comparison
model
medical device complication
drug bioavailability
hemoglobin
compartment model
candidiasis
body mass
clinical feature
drug efficacy
maximum concentration
age
central volume of distribution
drug blood level
blister
limb disease
Subjects
Details
- ISSN :
- 03125963
- Database :
- OpenAIRE
- Journal :
- CLINICAL PHARMACOKINETICS, r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, instname
- Accession number :
- edsair.RECOLECTA.....5990fd0e9af1585d9f94225fc647ca02