Pharmacokinetics Of Enoxaparin Research Articles

Characterizing Enoxaparin's Population Pharmacokinetics to Guide Dose Individualization in the Pediatric Population.

Pediatric dosing of enoxaparin was derived based on extrapolation of the adult therapeutic range to children. However, a large fraction of children do not achieve therapeutic anticoagulation with initial dosing. We aim to use real-world anti-Xa data obtained from children receiving enoxaparin per standard of care to characterize the population pharmacokinetics (PopPK).Author names: Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Also, kindly confirm the details in the metadata are correct.The author names are accurately presented and the metadata are correct. METHODS: A PopPK analysis was performed using NONMEM, and a stepwise covariate modeling approach was applied for the covariate selection. The final PopPK model, developed with data from 1293 patients ranging in age from 1 day to 18 years, was used to simulate enoxaparin subcutaneous dosing for prophylaxis and treatment based on total body weight (0-18 years, TBW) or fat-free mass (2-18 years, FFM). Simulated exposures in children with obesity (body mass index percentile ≥95th percentile) were compared with those without obesity. A linear, one-compartment PopPK model that included allometric scaling using TBW (<2 years) or FFM (≥2 years) characterized the enoxaparin pharmacokinetic data. In addition, serum creatinine was identified as a significant covariate influencing clearance. Simulations indicated that in patients aged <2 years, the recommended 1.5 mg/kg TBW-based dosing achieves therapeutic simulated concentrations. In pediatric patients aged ≥2 years, the recommended 1.0 mg/kg dose resulted in exposures more comparable in children with and without obesity when FFM weight-based dosing was applied. Using real-world data and PopPK modeling, enoxaparin's pharmacokinetics were characterized in pediatric patients. Using FFM and twice-daily dosing might reduce the risk of overdosing, especially in children with obesity.

Enoxaparin thromboprophylaxis in hospitalized obese pediatric patients.

Enoxaparin is an anticoagulant used for pharmacologic thromboprophylaxis in pediatrics. Enoxaparin pharmacokinetics can be altered in the setting of obesity. Optimal enoxaparin dosing for thromboprophylaxis in children with obesity remains unclear. A retrospective review was conducted of pediatric patients who weighed ≥60kg with BMI≥95th percentile, received enoxaparin for thromboprophylaxis, and had at least one appropriately drawn anti-factor Xa(anti-Xa) from 2013 to 2022. Anti-Xa levels were reviewed for patients initially treated with enoxaparin 30mg every 12h. The average daily enoxaparin dose required to achieve an anti-Xa of 0.2-0.4 unit/mL, which was stratified by BMI percentile and weight, was calculated. Of 116 patients (median age 15.8 years) included for analysis, 106 patients were initially treated with enoxaparin 30mg every 12h. Anti-Xa levels were<0.2 unit/mL in 53% of patients with BMI>99th percentile and 54% of patients>100kg. Ninety-one patients had at least one anti-Xa 0.2-0.4unit/mL with an average daily enoxaparin dosing of 66mg. When stratified by severity of obesity, higher doses were required to attain an anti-Xa 0.2-0.4 unit/mL in patients with BMI>99th percentile compared with those with 95th-99th percentile (67.8±15.7 vs. 62±5.6mg/day, p=.01). Patients>100kg required significantly higher dose than those ≤100kg (69.1±15.5 vs 61.2±7.3mg/day, p=.002). Increased initial dosing and/or anti-Xa level monitoring should be considered in adolescents with severe obesity receiving enoxaparin thromboprophylaxis.

Optimal dosing of enoxaparin in overweight and obese children.

Current enoxaparin dosing guidelines in children are based on total body weight. This is potentially inappropriate in obese children as it may overestimate the drug clearance. Current evidence suggests that obese children may require lower initial doses of enoxaparin, therefore the aim of this work was to characterise the pharmacokinetics of enoxaparin in obese children and to propose a more appropriate dosing regimen. Data from 196 unique encounters of 160 children who received enoxaparin treatment doses were analysed. Enoxaparin concentration was quantified using the chromogenic anti factor Xa (anti-Xa) assay. Patients provided a total of 552 anti-Xa samples. Existing published pharmacokinetic (PK) models were fitted and evaluated against our dataset using prediction-corrected visual predictive check plots (pcVPCs). A PK model was fitted using a nonlinear mixed-effects modelling approach. The fitted model was used to evaluate the current standard dosing and identify an optimal dosing regimen for obese children. Published models of enoxaparin pharmacokinetics in children did not capture the pharmacokinetics of enoxaparin in obese children as shown by pcVPCs. A one-compartment model with linear elimination best described the pharmacokinetics of enoxaparin. Allometrically scaled fat-free mass with an estimated exponent of 0.712 (CI 0.66-0.76) was the most influential covariate on clearance while linear fat-free mass was selected as the covariate on volume. Simulations from the model showed that fat-free mass-based dosing could achieve the target anti-Xa activity at steady state in 77.5% and 78.2% of obese and normal-weight children, respectively, compared to 65.2% and 75.5% for standard total body weight-based dosing. A population PK model that describes the time course of anti-Xa activity of enoxaparin was developed in a paediatric population. Based on this model, a unified dosing regimen was proposed that will potentially improve the success rate of target attainment in overweight/obese patients without the need for patient body size categorisation. Therefore, prospective validation of the proposed approach is warranted.

Pharmacokinetics of enoxaparin in COVID-19 critically ill patients

BackgroundIn intensive-care unit (ICU) patients, pathophysiological changes may affect the pharmacokinetics of enoxaparin and result in underdosing. ObjectivesTo develop a pharmacokinetic model of enoxaparin to predict the time-exposure profiles of various thromboprophylactic regimens in COVID-19 ICU-patients. MethodsThis was a retrospective study in ICUs of two French hospitals. Anti-Xa activities from consecutive patients with laboratory-confirmed SARS-CoV-2 infection treated with enoxaparin for the prevention or the treatment of venous thrombosis were used to develop a population pharmacokinetic model using non-linear mixed effects techniques. Monte Carlo simulations were then performed to predict enoxaparin exposure at steady-state after three days of administration. ResultsA total of 391 anti-Xa samples were measured in 95 patients. A one-compartment model with first-order kinetics best fitted the data. The covariate analysis showed that enoxaparin clearance (typical value 1.1 L.h-1) was related to renal function estimated by the CKD-EPI formula and volume of distribution (typical value 17.9 L) to actual body weight.Simulation of anti-Xa activities with enoxaparin 40 mg qd indicated that 64% of the patients had peak levels within the range 0.2 to 0.5 IU.mL-1 and 75% had 12-hour levels above 0.1 IU.mL-1. Administration of a total daily dose of at least 60 mg per day improved the probability of target attainment. ConclusionIn ICU COVID-19 patients, exposure to enoxaparin is reduced due to an increase in the volume of distribution and clearance. Consequently, enoxaparin 40 mg qd is suboptimal to attain thromboprophylactic anti-Xa levels.

Venous thromboembolism in burns patients: Are we underestimating the risk and underdosing our prophylaxis?

Burns patients exhibit all factors of Virchow's triad and are thus at high theoretical risk of venous thromboembolism (VTE). At our tertiary referral burns unit, a standard dose of low molecular weight heparin, which acts primarily by inhibiting Factor Xa, is given for thromboprophylaxis. However, the pharmacokinetics of enoxaparin are altered following a burn injury, and thus burns patients are likely underdosed on their thromboprophylaxis. The objectives of this study were to determine the incidence and risk factors for VTE among burns patients at the Victorian Adult Burns Service (VABS) and to determine the adequacy of the current enoxaparin thromboprophylaxis regimen through measurement of anti-factor Xa (AFXa) levels and comparison with established reference ranges. This study consisted of two parts. In part 1, the Burns Registry of Australia and New Zealand (BRANZ) was reviewed for cases of VTE in burns patients admitted to the VABS from 2013 - 2018. Part 2 was a prospective study that determined peak and trough AFXa levels in patients admitted to the VABS with >10% total body surface area (TBSA) burns. Part 1. Totally, 1,475 patients were admitted to the VABS between 2013 - 2018. There were 20 cases of VTE (1.36%). Percent TBSA of burn (OR = 1.04, 95% CI: 1.03 - 1.06), full thickness burns (OR = 2.78, 95% CI: 1.15 - 6.73), ICU admission (OR = 15.08, 95% CI: 5.01 - 45.44), mechanical ventilation (OR = 10.62, 95% CI: 4.05 - 27.91), operative procedures (OR = 1.43, 95% CI: 1.29 - 1.59), and a longer hospital stay (OR = 1.05, 95% CI: 1.04 - 1.07) were all associated with an increased VTE risk. Part 2. A total of 20 participants with >10% TBSA burns were recruited to the prospective study. Peak anti Factor Xa (AFXa) levels were measured for all 20 participants with 15% recording an initial prophylactic peak AFXa level within reference range. Upon subsequent measurements, 50% of participants reached a prophylactic peak AFXa level. Trough AFXa levels were measured for 17 participants with no participant recording an initial or subsequent trough AFXa level at or above the prophylactic threshold. Our study demonstrates a high incidence of VTE among burns patients at the VABS, especially among the major burns patients, and a thromboprophylaxis protocol that is ineffective in achieving prophylactic levels of AFXa level. The evidence suggests a need to evaluate different dosing protocols among burns patients in order to improve AFXa levels, with the aim of decreasing incidence of VTE in high-risk patients.

Population pharmacokinetics of enoxaparin in early stage of paediatric liver transplantation.

Preventing post-liver transplantation (LT) hepatic artery and portal vein thrombosis includes enoxaparin administration. Enoxaparin pharmacokinetics (PK) has not been investigated in children following LT. We described an enoxaparin PK model in 22 children the first week following LT. Anti-Xa activity time-courses were analysed using a nonlinear mixed effects approach with Monolix version 2016R. Anti-Xa activity time-courses were well described by a one-compartment model with first order absorption and elimination. Bodyweight prior to surgery (BWPREOP ) and the related postoperative variation (BW(t)) were the main covariates explaining CL and V between subject variabilities. Parameter estimates were CLi =CLTYP * (BWPREOP /70)3/4 ; Vi =VTYP * (BW(t)/70)1 ; where typical clearance (CLTYP ) and typical volume of distribution (VTYP ) were 1.23lh-1 and 14.6l, respectively. Standard dosing regimens of 50IUkg-1 12h-1 were insufficient to reach the target range of anti-Xa activity of 0.2-0.4IUml-1 . Specifically, seven children (32%) never attained the target range during the whole period of treatment and all children were at least once underdosed. According to the final results, we simulated individualized dosing regimens within 4h following the first administration. More than 100IUkg-1 12h-1 are suggested to reach the target range of anti-Xa activity of 0.2-0.4IUml-1 from the first day. Thanks to this model, the initial and maintenance doses could be assessed to rapidly achieve the target range. Higher doses per kg, especially in the youngest children, are suggested.

Population Pharmacokinetics of Enoxaparin in Pediatric Patients.

There are no studies evaluating the pharmacokinetics of enoxaparin in the hospitalized pediatric patient population. To characterize the pharmacokinetics of enoxaparin in pediatric patients. A retrospective review of inpatients 1 to 18 years of age admitted to our institution who received enoxaparin with anti-factor Xa activity level monitoring was performed. Demographic variables, enoxaparin dosing, and anti-factor Xa activity levels were collected. Population pharmacokinetic analysis was performed with bootstrap analysis. Simulation (n = 10 000) was performed to determine the percentage who achieved targeted anti-Xa levels at various doses. A total of 853 patients (male 52.1%, median age = 12.2 years; interquartile range [IQR] = 4.6-15.8 years) received a mean enoxaparin dose of 0.86 ± 0.31 mg/kg/dose. A median of 3 (IQR = 1-5) anti-factor Xa levels were sampled at 4.4 ± 1.3 hours after a dose, with a mean anti-factor Xa level of 0.52 ± 0.23 U/mL. A 1-compartment model best fit the data, and significant covariates included allometrically scaled weight, serum creatinine, and hematocrit on clearance, and platelets on volume of distribution. Simulations were run for patients both without and with reduced kidney function (creatinine clearance of ≤30 mL/min/1.73 m2). A dose of 1 mg/kg/dose every 12 hours had the highest probability (72.3%) of achieving an anti-Xa level within the target range (0.5-1 U/mL), whereas a dose reduction of ~30% achieved the same result in patients with reduced kidney function. Pediatric patients should initially be dosed at 1-mg/kg/dose subcutaneously every 12 hours for treatment of thromboembolism followed by anti-Xa activity monitoring. Dose reductions of ~30% for creatinine clearance ≤30 mL/min/1.73 m2 are required.

Enoxaparin Dosing Requirements and Anti-Xa Monitoring in Specialty Patient Populations: A Case Series of Pediatric; Renal-Impaired; Extremes of Body Weight; and Pregnant Patients

The use of enoxaparin in specialty populations has been excluded from clinical trials, including those with renal dysfunction, extremeness of body weight, pregnant patients, and pediatric patients. Much of the data of enoxaparin in these patients is derived from pharmacokinetics. Monitoring anti-factor Xa activity (Anti-Xa) to measure the anticoagulant effects may be of benefit. This retrospective review was conducted to evaluate if specialty patient populations admitted to a hospital setting had a peak Anti-Xa measured to guide in optimal enoxaparin dosing. A case series of patients admitted to New York University Langone Medical Center (NYULMC) between December 2012 and July 2014 who received at least three consecutive doses of enoxaparin for the treatment of VTE and had a peak Anti-Xa level drawn at steady state were evaluated. Patients were included if they were ≤18 years of age or if they were >18 years of age and met one of the following criteria: Pregnant, creatinine clearance (CrCl) ≤30 ml/min at time of initiation of enoxaparin, body weight ≤50 kg or ≥120 kg. A total of 31 patients were included in the analysis. The percentage of patients that achieved a therapeutic Anti-Xa level (0.5-1.2 IU/mL for twice daily enoxaparin or 1-2 IU/mL for once daily enoxaparin) at the time of the first Anti-Xa level drawn was greatest for the obese patients (100%) followed by pregnancy (67%), low body weight (57%), renal impaired (33-40%), and lastly pediatrics (9%). Additionally, neonates and young children required increased enoxaparin dosing to achieve therapeutic Anti-Xa. Optimal dosing of enoxaparin in specialty populations has not been established. Surrogate laboratory monitoring of peak Anti-Xa levels may help predict the pharmacokinetics of enoxaparin. Higher initial doses of enoxaparin may be needed in pediatric patients to attain therapeutic Anti-Xa levels.

Assessing an enoxaparin dosing protocol in morbidly obese patients.

The effect of obesity on the pharmacokinetics of enoxaparin is not clearly understood and traditional treatment doses in morbidly obese patients (body mass index [BMI]>40kg/m(2)) can lead to over anticoagulation. Our institution developed an inpatient protocol with reduced enoxaparin doses (0.75mg/kg/dose based on actual body weight) for patients with a weight >200kg or BMI>40kg/m(2). The primary objective was to determine if modified enoxaparin treatment doses would achieve therapeutic anti-Xa levels (goal range 0.6-1.0IU/mL) in morbidly obese patients. Thirty-one patients were included in our study and had a median body weight of 138kg (range 105-197) and a median BMI of 46.2kg/m(2) (range 40.1-62). The initial peak anti-Xa levels were in therapeutic range in 15 of 31 patients (48%) with an initial mean anti-Xa level of 0.92IU/mL. Twenty-four patients (77%) achieved therapeutic anti-Xa levels in goal range during their hospitalization, with a mean enoxaparin dose of 0.71mg/kg. Bleeding and thrombotic events were minimal and all patients that achieved an anti-Xa level in goal range did so with a dose less than 1mg/kg of enoxaparin.

Circulation : Clinical Summaries

<i>Circulation</i> : Clinical Summaries

Pharmacokinetic analysis of enoxaparin in a term neonate and review of literature

Enoxaparin is frequently used now in pediatric and neonatal care due to an increase in invasive procedures with secondary thrombotic episodes [1]. The two peaks of enoxaparin use in pediatrics are in newborns and adolescents [2–4]. Enoxaparin is easier to monitor than standard unfractionated heparin [5] but little is known about neonatal enoxaparin pharmacokinetics, dosing and target anti-Xa levels specific to neonates. Knowledge about pharmacokinetics in neonatal overdose is more limited [6,7].

Population Pharmacokinetics of Enoxaparin in Children at Risk for Symptomatic Thromboembolism.

Abstract 1071Poster Board I-93 Introduction:Enoxaparin, a low-molecular-weight-heparin (LMWH), is used off-label in children to prevent symptomatic thromboembolism when acute anticoagulation or secondary prevention is required due to venous thrombosis or stroke. This investigation was conducted because of concerns of altered pharmacokinetics and a lack of safety and efficacy data when used in children. Patients and Methods:Data of 126 children and adolescents with a median age of 5.9 years receiving enoxaparin either as a once or twice daily dosing regimen were analyzed. Children < 12 months of age received a starting dose of 1.5 mg/kg followed by a maintenance dose of 1.3 mg/kg. Children > 12 months of age were started on 1 mg/kg followed by a maintenance dose of 1 mg/kg. Blood samples were drawn after patients reached steady-state on their maintenance dose at baseline prior to the next dose, and at 2, 4, 8 and 12 hours after administration. The median enoxaparin concentration in our population resulted in a median anti-factor Xa activity of 0.4 U/ml (range 0 – 1 U/ml anti-factor Xa). By means of population pharmacokinetics using nonlinear mixed-effects modelling (NONMEM) plasma concentration-time data were analyzed. Several covariates such as age, body weight and body surface area were tested on their effects on the pharmacokinetic parameters. Results:Using a two-compartment model the enoxaparin kinetics were described sufficiently. By using body weight and age as covariates for clearance (CL) and central volume of distribution (V1) the best results were obtained. The final population estimates of enoxaparin resulted to be: CL 7.11 ml h-1 kg-1 ± 14.3%, V1 7.31 ml kg-1 ± 33.5%, intercompartimental clearance (Q) 194 ml h-1 ± 24.7%, peripheral volume of distribution (V2) 45.1 l ± 52.5% and absorption rate (ka) 0.0799 h-1 ± 21.7% (estimates ± standard errors). Interindividual variability (IIV) was found to be 75.6% for CL and 78.4% for Q, respectively. Figure 1 shows the predicted activity time-course versus the measured activities for a representative patient. The model is capable of describing all aging and dosing groups of our childhood population (neonates, infants to adolescents). Conclusion:The high IIV in CL and Q in our population underlines the need for monitoring the activity and individualizing the dose. Further population pharmacokinetic/-dynamic investigations should be conducted to predict target enoxaparin levels or other new antithrombotic drugs for more safety and efficacy during antithrombotic therapy when used in children. [Display omitted] Disclosures:Off Label Use: Enoxaparin (LMWH) is used off-label in children to prevent symptomatic thromboembolism..

Changes in Enoxaparin Pharmacokinetics During Pregnancy and Implications for Antithrombotic Therapeutic Strategy

Changes in Enoxaparin Pharmacokinetics During Pregnancy and Implications for Antithrombotic Therapeutic Strategy

Changes in Enoxaparin Pharmacokinetics During Pregnancy and Implications for Antithrombotic Therapeutic Strategy

Enoxaparin is frequently prescribed for pregnant women who are at high risk for thromboembolic complications. We conducted a population pharmacokinetics study with 75 pregnant women and 38 nonpregnant women as controls to evaluate enoxaparin pharmacokinetics during pregnancy and the postpartum period. Clearance of the drug was higher in the pregnant women throughout pregnancy when compared with nonpregnant women (0.78 +/- 0.03 l/h vs. 0.52 +/- 0.03 l/h, respectively P < 0.001) with the stage of the pregnancy having no influence. The volume of distribution was influenced by stage of the pregnancy, characterized by a two-step increase, with an initial rise paralleling the woman's increase in body weight during the first two trimesters, followed by an additional increase of 41% during the last 2 months of pregnancy, independent of changes in weight. Using enoxaparin pharmacokinetic parameters to simulate anti-Xa time profiles, we observed that the maintenance of the same doses throughout pregnancy resulted in a progressive reduction in mean and peak anti-Xa activities. We recommend the administration of doses normalized for body weight changes so as to counteract enoxaparin pharmacokinetic changes that accompany various stages of pregnancy.

Development of an Efficient Sampling Strategy to Predict Enoxaparin Pharmacokinetics in Stage 5 Chronic Kidney Disease

Patients with renal dysfunction are at greater risk for hemorrhagic events than patients with normal renal function. The objective of this study was to develop an efficient sampling strategy that optimally predicts anti-Xa activity exposure after enoxaparin administration in patients with chronic kidney disease to optimize enoxaparin therapy. The antifactor Xa activity data of 8 anuric patients who were administered 1 mg/kg enoxaparin immediately after hemodialysis were used for the development of the optimal sampling strategies. Maximum A Posteriori Bayesian (MAPB) priors were developed by pharmacokinetic analysis. The 2, 3, and 4 D-optimal sampling designs were determined and Monte Carlo simulations using the MAPB estimator were performed. The original model with the estimator was used to determine the predictive power of the sampling schemes. The most efficient sampling scheme (OSS-2) was accurate and precise in predicting apparent enoxaparin clearance (-3.2% bias, 6.5% precision). The addition of a third sampling time at 30 minutes (OSS-3) was more accurate (P < 0.01) and precise (P < 0.01) than OSS-2 at predicting the rate of absorption (ka) but did not improve the accuracy (P > 0.05) or precision (P = 0.20) of the CLs/F estimate. The determination of antifactor Xa activity at 5 and 24 hours, along with the Bayesian estimators generated from this study, accurately and precisely predict the apparent clearance of antifactor Xa activity. This sampling strategy may be used for therapeutic drug monitoring of enoxaparin and for future clinical trials in patients with chronic kidney disease.

The Pharmacokinetics of Enoxaparin Do Not Correlate With Its Pharmacodynamic Effect in Patients Receiving Dialysis Therapies

The pharmacokinetics and pharmacodynamics of enoxaparin were studied in healthy volunteers and hemodialysis and peritoneal dialysis subjects. Antifactor Xa activity estimated the pharmacokinetics, whereas thrombin generation time (TGT) estimated the pharmacodynamics. Enoxaparin 1 mg/kg was given subcutaneously to all subjects. Antifactor Xa Amax and AUC(0-12) were similar between groups, but the TGTmax was significantly greater in the dialysis groups (P = .001). The thrombin generation time remained significantly more prolonged throughout the 12-hour study period, and there was a trend toward greater TGT AUEC(0-12) for both dialysis groups (P = .07). Patients receiving hemodialysis had greater sensitivity to enoxaparin compared to the other groups. These results suggest that in dialysis patients, there may be accumulation of active heparin metabolites that are undetected by the antifactor Xa assay. Therefore, these subjects exhibit greater thrombin generation time prolongation despite similar antifactor Xa exposure. Further large-scale studies are needed to corroborate the results of this exploratory pilot study.

Rapid Point Coagulation ENOX Test in Patients With Altered Pharmacokinetics of Enoxaparin

Background: As the role of enoxaparin expands in the therapeutic armamentarium, so does the role of diagnostic tools, especially the ones that have an edge over the traditional laboratory tests by virtue of being inexpensive, rapid, and accurate. The Rapid Point Coagulation enoxaparin test (ENOX), one such point-of-care test, is designed to determine the anticoagulation effect of enoxaparin. It is emerging as a useful tool, not only in patients undergoing percutaneous coronary interventions, but also in patients whose response to enoxaparin is difficult to predict. We chose to conduct a study to evaluate the usefulness of this bedside test in patients with altered pharmacokinetics of enoxaparin. Methods: This is a correlation study that enrolled 35 patients between April 2003 and November 2003 with renal insufficiency (creatinine clearance <60 mL/min, n = 25), obesity (weight >100 kg, n = 7), and malnourishment (weight <40 kg, n = 3). Whole blood samples were collected from each of the 35 patients, 4 to 8 hours after administration of subcutaneous dose of enoxaparin, in various clinical settings (pulmonary embolism, acute coronary syndrome, atrial fibrillation and deep venous thrombosis). ENOX time and anti-Xa levels were measured simultaneously. Results: A scatter diagram was plotted with ENOX time on the y-axis and anti-Xa levels on the x-axis. The Pearson's correlation coefficient was calculated to be 0.87. A strong degree of agreement between ENOX time and anti-Xa levels was therefore established. Using the critical value table for Pearson's correlation coefficient, a P value of <0.05 was obtained. Anti-Xa level of 0.5–1.8 IU/mL correlated with ENOX time of 200 to 425 seconds, respectively. Conclusions: Clinicians often have reservations in using enoxaparin in patients in whom the response is unpredictable. Our study, although small, shows a strong correlation between the rapid bedside ENOX test and laboratory-based anti-Xa levels even in patients with altered pharmacokinetics. It therefore underscores the use of the point-of-care ENOX test and justifies, with reasonable confidence, the use of this drug in this subset of patients.

Reliable anticoagulation with enoxaparin in patients undergoing percutaneous coronary intervention: The pharmacokinetics of enoxaparin in PCI (PEPCI) study.

The objective of this study was to evaluate the pharmacokinetic response to intravenous (IV) enoxaparin given 8-12 hr after subcutaneous (SC) dosing in patients undergoing percutaneous coronary intervention (PCI). Fifty-five patients received SC enoxaparin (1 mg/kg every 12 hr) followed by an IV bolus (0.3 mg/kg) 8-12 hr after the last SC dose, at the start of PCI or during catheterization. Anti-Xa levels were within the target range in 98% of patients 2-8 hr after the last SC dose, in 96% of patients following the IV bolus, and in 91% of patients for a further 2 hr. Subcutaneous enoxaparin (1 mg/kg every 12 hr) provides sufficient anti-Xa levels for PCI 2-8 hr after the last dose. An additional 0.3 mg/kg enoxaparin dose given IV 8-12 hr after the last SC dose reliably maintains anti-Xa levels within the target for at least 2 additional hr.

The pharmacokinetics of subcutaneous enoxaparin in end-stage renal disease.

To evaluate the pharmacokinetics of enoxaparin in end-stage renal disease (ESRD), and determine if dosage reduction is necessary to maintain antifactor Xa activity concentrations within the therapeutic range. Prospective, single-dose pharmacokinetic study. University-affiliated general clinical research center. Eight nonthrombosed patients with ESRD requiring hemodialysis. All subjects received a single dose of enoxaparin sodium 1 mg/kg subcutaneously and had serial plasma antifactor Xa activity concentrations measured over 24 hours. The pharmacokinetics of enoxaparin were determined from plasma antifactor Xa activity concentrations, and various multiple-dose regimens were simulated. After administration of the drug, total body clearance was 14.6 ml/minute and there was a 2-fold prolongation in antifactor Xa activity half-life compared with values reported in healthy subjects. All other pharmacokinetic parameters were similar to those in healthy subjects and patients with chronic renal insufficiency. An accumulation ratio of 1.6 was estimated for a dosing interval of every 12 hours based on single-dose pharmacokinetics. When various therapeutic regimens were simulated to predict average steady-state antifactor Xa activity, standard enoxaparin dosages of 1 mg/kg subcutaneously every 12 hours and 1.5 mg/kg every 24 hours resulted in average steady-state concentrations within the therapeutic range. Based on antifactor Xa activity, ESRD has little effect on the pharmacokinetics of enoxaparin, and dosing adjustments are unnecessary.