scholarly journals Compartmental Pharmacokinetics and Tissue Distribution of Multilamellar Liposomal Nystatin in Rabbits

2000 ◽  
Vol 44 (4) ◽  
pp. 950-957 ◽  
Author(s):  
Andreas H. Groll ◽  
Diana Mickiene ◽  
Kathy Werner ◽  
Ruta Petraitiene ◽  
Vidmantas Petraitis ◽  
...  
Keyword(s):  
Tissue Distribution ◽  
Fungal Infections ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Pharmacokinetic Parameters ◽  
Nonlinear Kinetics ◽  
Multiple Dosing ◽  
Concentration Data ◽  
Chromatography Method ◽  
Dose Dependent

ABSTRACT The plasma pharmacokinetics of multilamellar liposomal nystatin were studied in normal, catheterized rabbits after single and multiple daily intravenous administration of dosages of 2, 4, and 6 mg/kg of body weight, and drug levels in tissues were assessed after multiple dosing. Concentrations of liposomal nystatin were measured as those of nystatin by a validated high-performance liquid chromatography method, and plasma concentration data were fitted into a two-compartment open model. Across the investigated dosage range, liposomal nystatin demonstrated nonlinear kinetics with more than proportional increases in the AUC0–24 and decreasing clearance, consistent with dose-dependent tissue distribution and/or a dose-dependent elimination process. After single-dose administration, the meanC max increased from 13.07 μg/ml at 2 mg/kg to 41.91 μg/ml at 6 mg/kg (P < 0.001); the AUC0–24 changed from 11.65 to 67.44 μg · h/ml (P < 0.001), the Vd changed from 0.205 to 0.184 liters/kg (not significant), the CL t from 0.173 to 0.101 liters/kg · h (P < 0.05), and terminal half-life from 0.96 to 1.51 h (P < 0.05). There were no significant changes in pharmacokinetic parameters after multiple dosing over 14 days. Assessment of tissue concentrations of nystatin near peak plasma levels after multiple dosing over 15 days revealed preferential distribution to the lungs, liver, and spleen at that time point. Substantial levels were also found in the urine, raising the possibility that renal excretion may play a significant role in drug elimination. Liposomal nystatin administered to rabbits was well tolerated and displayed nonlinear pharmacokinetics, potentially therapeutic peak plasma concentrations, and substantial penetration into tissues. Pharmacokinetic parameters were very similar to those observed in patients, thus validating results derived from infection models in the rabbit and allowing inferences to be made about the treatment of invasive fungal infections in humans.

scholarly journals Compartmental Pharmacokinetics and Tissue Distribution of the Antifungal Echinocandin Lipopeptide Micafungin (FK463) in Rabbits

2001 ◽  
Vol 45 (12) ◽  
pp. 3322-3327 ◽  
Author(s):  
Andreas H. Groll ◽  
Diana Mickiene ◽  
Vidmantas Petraitis ◽  
Ruta Petraitiene ◽  
Khalid H. Ibrahim ◽  
...  
Keyword(s):  
Tissue Distribution ◽  
Fungal Infections ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Plasma Drug ◽  
Concentration Data ◽  
Time Curve ◽  
Concentration Time ◽  
Drug Concentrations ◽  
Plasma Pharmacokinetics

ABSTRACT The plasma pharmacokinetics and tissue distribution of the novel antifungal echinocandin-like lipopeptide micafungin (FK463) were investigated in healthy rabbits. Cohorts of three animals each received micafungin at 0.5, 1, and 2 mg/kg of body weight intravenously once daily for a total of 8 days. Serial plasma samples were collected on days 1 and 7, and tissue samples were obtained 30 min after the eighth dose. Drug concentrations were determined by validated high-performance liquid chromatographic methods. Plasma drug concentration data were fit to a two-compartment pharmacokinetic model, and pharmacokinetic parameters were estimated using weighted nonlinear least-square regression analysis. Micafungin demonstrated linear plasma pharmacokinetics without changes in total clearance and dose-normalized area under the concentration-time curve from 0 h to infinity. After administration of single doses to the rabbits, mean peak plasma drug concentrations ranged from 7.62 μg/ml at 0.5 mg/kg to 16.8 μg/ml at 2 mg/kg, the area under the concentration-time curve from 0 to 24 h ranged from 5.66 to 21.79 μg · h/ml, the apparent volume of distribution at steady state ranged from 0.296 to 0.343 liter/kg, and the elimination half-life ranged from 2.97 to 3.20 h, respectively. No significant changes in pharmacokinetic parameters and no accumulation was noted after multiple dosing. Mean tissue micafungin concentrations 30 min after the last of eight daily doses were highest in the lung (2.26 to 11.76 μg/g), liver (2.05 to 8.82 μg/g), spleen (1.87 to 9.05 μg/g), and kidney (1.40 to 6.12 μg/g). While micafungin was not detectable in cerebrospinal fluid, the concentration in brain tissue ranged from 0.08 to 0.18 μg/g. These findings indicate linear disposition of micafungin at dosages of 0.5 to 2 mg/kg and achievement of potentially therapeutic drug concentrations in plasma and tissues that are common sites of invasive fungal infections.

scholarly journals Comparative Drug Disposition, Urinary Pharmacokinetics, and Renal Effects of Multilamellar Liposomal Nystatin and Amphotericin B Deoxycholate in Rabbits

2003 ◽  
Vol 47 (12) ◽  
pp. 3917-3925 ◽  
Author(s):  
Andreas H. Groll ◽  
Diana Mickiene ◽  
Vidmantas Petraitis ◽  
Ruta Petraitiene ◽  
Raul M. Alfaro ◽  
...  
Keyword(s):  
Total Dose ◽  
Amphotericin B ◽  
Drug Disposition ◽  
Fungal Infections ◽  
Standard Dose ◽  
Concentration Data ◽  
Drug Concentrations ◽  
Amphotericin B Deoxycholate ◽  
Dose Dependent Decrease ◽  
Dose Dependent

ABSTRACT The comparative drug dispositions, urinary pharmacokinetics, and effects on renal function of multilamellar liposomal nystatin (LNYS; Nyotran) and amphotericin B deoxycholate (DAMB; Fungizone) were studied in rabbits. Drug concentrations were determined by high-performance liquid chromatography as total concentrations of LNYS and DAMB. In comparison to a standard dose of 1 mg of DAMB/kg of body weight, therapeutic dosages of LNYS, i.e., 2, 4, and 6 mg/kg, resulted in escalating maximum concentrations (C max) (17 to 56μ g/ml for LNYS versus 3.36 μg/ml for DAMB; P< 0.001) and values for the area under the concentration-time curve from 0 to 24 h (AUC0-24) (17 to 77μ g · h/ml for LNYS versus 12μ g · h/ml for DAMB; P < 0.001) in plasma but a significantly faster total clearance from plasma (0.117 to 0.080 liter/h/kg for LNYS versus 0.055 liter/h/kg for DAMB; P = 0.013) and a ≤8-fold-smaller volume of distribution at steady state (P = 0.002). Urinary drug concentration data revealed a ≥10-fold-higher C max (16 to 10 μg/ml for LNYS versus 0.96μ g/ml for DAMB; P = 0.015) and a 4- to 7-fold-greater AUC0-24 (63 to 35μ g · h/ml for LNYS versus 8.9μ g · h/ml for DAMB; P = 0.015) following the administration of LNYS, with a dose-dependent decrease in the dose-normalized AUC0-24 in urine (P= 0.001) and a trend toward a dose-dependent decrease in renal clearance. Except for the kidneys, the mean concentrations of LNYS in liver, spleen, and lung 24 h after dosing were severalfold lower than those after administration of DAMB (P,<0.002 to <0.001). Less than 1% each of the total dose of LNYS was recovered from the kidneys, liver, spleen, and lungs; in contrast, a quarter of the total dose was recovered from the livers of DAMB-treated animals. LNYS had dose-dependent effects on glomerular filtration and distal, but not proximal, renal tubular function which did not exceed those of DAMB at the highest investigated dosage of 6 mg/kg. The results of this experimental study demonstrate fundamental differences in the dispositions of LNYS and DAMB. Based on its enhanced urinary exposure, LNYS may offer a therapeutic advantage in systemic fungal infections involving the upper and lower urinary tracts that require therapy with antifungal polyenes.

scholarly journals Compartmental Pharmacokinetics and Tissue Drug Distribution of the Pradimicin Derivative BMS 181184 in Rabbits

1998 ◽  
Vol 42 (10) ◽  
pp. 2700-2705 ◽  
Author(s):  
Andreas H. Groll ◽  
Tin Sein ◽  
Vidas Petraitis ◽  
Ruta Petraitiene ◽  
Diana Callender ◽  
...  
Keyword(s):  
Single Dose ◽  
Half Life ◽  
Peak Plasma ◽  
Volume Of Distribution ◽  
Multiple Dosing ◽  
Time Curve ◽  
Dose Administration ◽  
Single Dose Administration ◽  
Elimination Half ◽  
Dose Dependent

ABSTRACT The pharmacokinetics of the antifungal pradimicin derivative BMS 181184 in plasma of normal, catheterized rabbits were characterized after single and multiple daily intravenous administrations of dosages of 10, 25, 50, or 150 mg/kg of body weight, and drug levels in tissues were assessed after multiple dosing. Concentrations of BMS 181184 were determined by a validated high-performance liquid chromatography method, and plasma data were modeled into a two-compartment open model. Across the investigated dosage range, BMS 181184 demonstrated nonlinear, dose-dependent kinetics with enhanced clearance, reciprocal shortening of elimination half-life, and an apparently expanding volume of distribution with increasing dosage. After single-dose administration, the mean peak plasma BMS 181184 concentration (C max) ranged from 120 μg/ml at 10 mg/kg to 648 μg/ml at 150 mg/kg; the area under the concentration-time curve from 0 to 24 h (AUC0–24) ranged from 726 to 2,130 μg · h/ml, the volume of distribution ranged from 0.397 to 0.799 liter/kg, and the terminal half-life ranged from 4.99 to 2.31 h, respectively (P < 0.005 toP < 0.001). No drug accumulation in plasma occurred after multiple daily dosing at 10, 25, or 50 mg/kg over 15 days, although mean elimination half-lives were slightly longer. Multiple daily dosing at 150 mg/kg was associated with enhanced total clearance and a significant decrease in AUC0–24 below the values obtained at 50 mg/kg (P < 0.01) and after single-dose administration of the same dosage (P < 0.05). Assessment of tissue BMS 181184 concentrations after multiple dosing over 16 days revealed substantial uptake in the lungs, liver, and spleen and, most notably, dose-dependent accumulation of the drug within the kidneys. These findings are indicative of dose- and time-dependent elimination of BMS 181184 from plasma and renal accumulation of the compound after multiple dosing.

Clinical Rules for Phenytoin Dosing

1993 ◽  
Vol 27 (10) ◽  
pp. 1169-1173 ◽  
Author(s):  
Michael D. Privitera
Keyword(s):  
Plasma Concentration ◽  
Plasma Concentrations ◽  
Test Group ◽  
Patient Data ◽  
Pharmacokinetic Parameters ◽  
Concentration Data ◽  
Simple Method ◽  
Actual Patient ◽  
Initial Plasma ◽  
Clinical Rules

OBJECTIVE: To develop simple clinical rules for dosing phenytoin (PHT) using computer simulations, then to test the rules for accuracy and safety on actual patient data. DESIGN: Patients with steady-state PHT plasma concentrations at least two different PHT doses were identified from three separate sources of patient data. A computerized dosing program calculated pharmacokinetic parameters using Bayesian methodology, then predicted how many patients were likely to reach potentially toxic PHT plasma concentrations when their daily dosage was increased by 30, 50, or 100 mg. Dosing rules were developed to allow fewer than ten percent of resultant plasma concentrations to exceed 25 μg/mL. The dosing rules then were tested on dose/plasma concentration data from a separate group of patients. SETTING: All patients were being treated by neurologists either as outpatients or inpatients. PATIENTS: All patients were adults with epilepsy being treated with PHT; none had clinically significant renal or hepatic disease. Patients for the computer simulation were from three sources: (1) patients who had an initial PHT plasma concentration <10 μg/mL and required a dosage increase; (2) patients admitted to the hospital for PHT intoxication; and (3) patients who required consultations specifically for PHT dosing. Patients on whom the dosing rules were tested were part of a prospective, randomized trial of antiepileptic drug safety and efficacy. MAIN OUTCOME MEASURES: Successful dosing rules allowing fewer than ten percent of resulting plasma concentrations in the test group to exceed 25 μg/mL. RESULTS: The simulations used 167 actual dose/plasma concentration pairs from 45 patients. The resulting dosing rules were: increase the dosage by 100 mg/d if the initial plasma concentration was <7 μg/mL; increase the dosage by 50 mg/d if the initial plasma concentration is 7 to <12 μg/mL; increase the dosage by 30 mg/d if the initial plasma concentration is ≥12 μg/mL. The rules were tested on 129 50- or 100-mg dosage increases in 77 patients. All 53 dosage increases that were within the dosing rules produced plasma concentrations <25 μg/mL, whereas 36 percent (27 of 74) of the dosage increases that exceeded the dosing rules produced plasma concentrations >25 μg/mL. CONCLUSIONS: The proposed dosing rules are a simple method for clinicians to estimate PHT dosage changes and appear to be safe and accurate when applied retrospectively to actual patient data.

scholarly journals Pharmacokinetics of Buprenorphine and Sustained-release Buprenorphine in Common Marmosets (Callithrix jacchus)

2020 ◽  
Author(s):  
Casey B Fitz ◽  
Anna E Goodroe ◽  
David E Moody ◽  
Wenfang B Fang ◽  
Saverio V Capuano III
Keyword(s):  
Adverse Effects ◽  
Sustained Release ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Callithrix Jacchus ◽  
Terminal Phase ◽  
Pharmacokinetic Parameters ◽  
Common Marmosets ◽  
Adult Age ◽  
Concentration Time

Buprenorphine is an essential component of analgesic protocols in common marmosets (Callithrix jacchus). The use of buprenorphine HCl (BUP) and sustained-release buprenorphine (BSR) formulations has become commonplace in this species, but the pharmacokinetics have not been evaluated. Healthy adult (age, 2.4 to 6.8 y; 6 female and 6 male) common marmosets were enrolled in this study to determine the pharmacokinetic parameters, plasma concentration–time curves, and any apparent adverse effects of these compounds. Equal numbers of each sex were randomly assigned to receive BUP (0.02 mg/kg IM) orBSR (0.2 mg/kg SC), resulting in peak plasma concentrations (mean ± 1 SD) of 15.2 ± 8.1 and 2.8 ± 1.2 ng/mL, terminal phase t1/2 of 2.2 ± 1.0 and 32.6 ± 9.6 h, and AUC0-last of 16.1 ± 3.7 and 98.6 ± 42.7 ng×h/mL. The plasma concentrations of buprenorphine exceeded the proposed minimal therapeutic threshold (0.1 ng/mL) at 5 and 15 min after BUP and BSR administration,showing that both compounds are rapid-acting, and remained above that threshold through the final time points of 8 and 72h. Extrapolation of the terminal elimination phase of the mean concentration–time curves was used to develop the clinical dosing frequencies of 6 to 8 h for BUP and 3.0 to 3.5 d for BSR. Some adverse effects were observed after the administration of BUP to common marmosets in this study, thus mandating judicious use in clinical practice. BSR provided a safe, long-acting option for analgesia and therefore can be used to refine analgesic protocols in this species.

scholarly journals Gender differences in concentration of itraconazole and hydroxyitraconazole

2021 ◽  
Vol 27 (1) ◽  
pp. 7-18
Author(s):  
Tijana Stanojković ◽  
Milijana Miljković ◽  
Nemanja Rančić ◽  
Aleksandra Kovačević ◽  
Viktorija Dragojević-Simić
Keyword(s):  
Single Dose ◽  
Plasma Concentrations ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Time Intervals ◽  
Chromatography Method ◽  
Oral Application ◽  
First Pass ◽  
Liquid Chromatography Method ◽  
Pass Through

Introduction: Itraconazole is an antifungal drug belonging to the triazole group. After oral application, it is rapidly absorbed, but its bioavailability is reduced due to an intensive first-pass through the liver metabolism effect. A large number of metabolites (the most important of which is hydroxyitraconazole) are produced by isoform CYP3A4 of cytochrome P450. The variability of itraconazole pharmacokinetics is the result of numerous factors that have not yet been fully clarified. Our study aimed to investigate the influence of gender on itraconazole and hydroxyitraconazole plasma concentrations in healthy adults after an oral application of a single dose of itraconazole. Methods: Pharmacokinetic analysis was performed after oral administration of itraconazole in a single dose of 100 mg to 22 male and 16 female healthy volunteers. Blood samples were collected before taking the drug and at appropriate time intervals up to 72 hours later. Itraconazole and hydroxyitraconazole concentrations were determined using a validated liquid chromatography method with mass spectrometric detection (LC-MS/MS) and their pharmacokinetic parameters were calculated by using the Kinetica programme, version 5.0: Cmax, Tmax, PIK (0-72), PIK (0-∞), T1/2, and Ke. Results: The median values of both itraconazole and hydroxyitraconazole were lower in women in comparison to men during the whole period of observation. Moreover, median values of Cmax, PIK(0-72) and PIK(0-∞) parameters were also significantly lower in women, concerning both itraconazole (p=0.005, 0.036 and 0.036, respectively) and its metabolite (p=0.004, 0.010 and 0.044, respectively). Elimination parameters - T1/2 and Ke did not differ between genders. Conclusion: Women were less exposed to itraconazole and its active metabolite than men following an oral application of the drug, possibly as a result of lower bioavailability due to a more intense pre-systemic metabolism, as a result of a higher expression and/or activity of the isoform enzyme, which metabolises itraconazole, and which would need to be confirmed by pharmacogenomic analysis.

scholarly journals Aspects of Theophylline Clearance in Children

1997 ◽  
Vol 25 (5) ◽  
pp. 497-501 ◽  
Author(s):  
B. J. Anderson ◽  
N. H. G. Holford ◽  
G. A. Woollard
Keyword(s):  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Parameter Estimates ◽  
Power Model ◽  
Theophylline Clearance ◽  
Concentration Data ◽  
Model Parameter ◽  
Age Related ◽  
Menten Constant

Michaelis-Menten pharmacokinetic parameters for theophylline were estimated in a three-month infant following an accidental overdose of intravenous aminophylline. Fitting of time-concentration data was performed using nonlinear regression with MKMODEL. A mixed order elimination model was superior to a first order model. Parameter estimates were standardized to a 70 kg human using an allometric power model. Parameter estimates (SE) were: maximum rate of metabolism (Vmax) 71(42) mg.h–1, Michaelis-Menten constant (Km) 32.3 (33.5) mg.l–1, volume of distribution (Vd) 46.9 (2.6) l. This Michaelis-Menten constant is lower than that reported for adults and consequently non-linear elimination will occur at lower plasma concentrations in infants than in adults. Theophylline clearance has traditionally been reported as directly proportional to body weight. This per kilogram model gives an erroneous impression that clearance is greatest in early childhood and then decreases with age until adult rates are reached in late adolescence. Age-related clearance values reported in the literature were reviewed using an allometric 3/4 power model. This size model demonstrates that clearance increases in infancy and reaches adult rates in the first one to two years of life.

scholarly journals Pharmacokinetic Study of Human Immunodeficiency Virus Protease Inhibitors Used in Combination with Amprenavir

2001 ◽  
Vol 45 (12) ◽  
pp. 3663-3668 ◽  
Author(s):  
Brian M. Sadler ◽  
Catherine Gillotin ◽  
Yu Lou ◽  
Joseph J. Eron ◽  
William Lang ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Steady State ◽  
Protease Inhibitors ◽  
Pharmacokinetic Study ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Plasma Concentrations ◽  
Pharmacokinetic Parameters ◽  
Open Label ◽  
Immunodeficiency Virus

ABSTRACT In an open-label, randomized, multicenter, multiple-dose pharmacokinetic study, we determined the steady-state pharmacokinetics of amprenavir with and without coadministration of indinavir, nelfinavir, or saquinavir soft gel formulation in 31 human immunodeficiency virus type 1-infected subjects. The results indicated that amprenavir plasma concentrations were decreased by saquinavir soft gel capsule (by 32% for area under the concentration-time curve at steady state [AUCss] and 37% for peak plasma concentration at steady state [C max,ss]) and increased by indinavir (33% for AUCss). Nelfinavir significantly increased amprenavir minimum drug concentration at steady state (by 189%) but did not affect amprenavir AUCss orC max,ss. Nelfinavir and saquinavir steady-state pharmacokinetics were unchanged by coadministration with amprenavir compared with the historical monotherapy data. Concentrations of indinavir, coadministered with amprenavir, in plasma decreased in both single-dose and steady-state evaluations. The changes in amprenavir steady-state pharmacokinetic parameters, relative to those for amprenavir alone, were not consistent among protease inhibitors, nor were the changes consistent with potential interactions in CYP3A4 metabolism or P-glycoprotein transport. No dose adjustment of either protease inhibitor in any of the combinations studied is needed.

scholarly journals Safety and Pharmacokinetics of Bevirimat (PA-457), a Novel Inhibitor of Human Immunodeficiency Virus Maturation, in Healthy Volunteers

2007 ◽  
Vol 51 (9) ◽  
pp. 3063-3066 ◽  
Author(s):  
David E. Martin ◽  
Robert Blum ◽  
John Wilton ◽  
Judy Doto ◽  
Hal Galbraith ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Oral Administration ◽  
Half Life ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Pharmacokinetic Parameters ◽  
Double Blind Study ◽  
Immunodeficiency Virus ◽  
Oral Doses

ABSTRACT Bevirimat (BVM; formerly known as PA-457) is a novel inhibitor of human immunodeficiency virus (HIV) maturation that is being developed for the treatment of HIV infection. The pharmacokinetics of this agent in healthy male volunteers were studied in a randomized, double-blind study in which the participants received single oral doses of placebo (n = 8) or escalating doses of BVM at 25, 50, 100, or 250 mg (n = 6 per dose); escalation was performed only after the pharmacokinetics and safety of the preceding dose had been evaluated. Plasma was collected over 480 h after dosing and urine was collected over 48 h after dosing for determination of the values of pharmacokinetic parameters. BVM was well absorbed after oral administration, with peak plasma concentrations being achieved 1 to 3 h after dosing. The half-life was 60 to 80 h. The exposure assessed by determination of the peak concentration and the area under the concentration-time curve was dose proportional. Single oral doses of BVM were well tolerated: there were no dose-limiting toxicities, and no serious adverse events were reported. These findings suggest that that BVM offers a favorable pharmacokinetic profile, with predictable pharmacokinetics following the oral administration of single doses. The long half-life of BVM may facilitate once-daily dosing.

scholarly journals Interindividual Variability of Apixaban Plasma Concentrations: Influence of Clinical and Genetic Factors in a Real-Life Cohort of Atrial Fibrillation Patients

Genes ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 438
Author(s):  
Adela-Nicoleta Roşian ◽  
Ştefan Horia Roşian ◽  
Bela Kiss ◽  
Maria Georgia Ştefan ◽  
Adrian Pavel Trifa ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Plasma Level ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Real Life ◽  
Pharmacokinetic Parameters ◽  
Liquid Chromatography Tandem Mass ◽  
Trough Concentrations ◽  
Abcb1 Genotype

(1) Background: Prescribing apixaban for stroke prevention has significantly increased in patients with non-valvular atrial fibrillation (NVAF). The ABCB1 genotype can influence apixaban absorption and bioavailability. The aim of the present study was to assess the factors that influence apixaban’s plasma level and to establish if a certain relationship has clinical relevance. (2) Methods: Fifty-three NVAF patients were treated with 5 mg apixaban twice/day (70.0 years, range: 65–77, 60.4% men). Trough and peak plasma concentrations of apixaban were determined by liquid chromatography-tandem mass-spectrometry (LC-MS/MS), and ABCB1 genotyping was performed. (3) Results: Apixaban plasma concentrations varied considerably. They were higher in women than in men (311.2 ng/dL vs. 252.2 ng/dL; p = 0.05) and were lower in patients with heart failure (149.4 ng/dL vs. 304.5 ng/dL; p < 0.01). Creatinine clearance was inversely correlated with the apixaban plasma level (Spearman correlation: r = −0.365; p = 0.007 for trough concentrations). No statistically significant differences between the genotypic groups of ABCB1 rs1045642 and ABCB1 rs4148738 were found in the trough or peak apixaban plasma concentrations. (4) Conclusions: Pharmacokinetic parameters are influenced by several clinical factors of which renal function is the major determinant. Plasma concentrations measured in women had higher values than those measured in men, and heart failure was associated with decreased plasma levels of apixaban.

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