Effect of Peritoneal Dialysis on Plasma and Peritoneal Fluid Concentrations of Isoniazid, Pyrazinamide, and Rifampin

2003 ◽  
Vol 23 (4) ◽  
pp. 362-367
Author(s):  
Curie Ahn ◽  
Kook-Hwan Oh ◽  
Kiwon Kim ◽  
Kyung Yi Lee ◽  
Jung Geon Lee ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Peritoneal Fluid ◽  
High Performance ◽  
Inhibitory Concentration ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Pharmacokinetic Analysis ◽  
Dialysis Patients ◽  
Pharmacokinetic Profiles ◽  
Fluid Concentration

♦ Objective This study was performed to elucidate the pharmacokinetic profiles of antimycobacterial regimens for peritoneal dialysis patients. ♦ Patients Nine patients on maintenance continuous ambulatory peritoneal dialysis (CAPD) were included in this study. ♦ Methods After administering a conventional oral dose of antituberculosis medications, we measured plasma and peritoneal fluid concentrations of isoniazid by fluorometry, and rifampin and pyrazinamide by high performance liquid chromatography. The assay data were subjected to pharmacokinetic analysis. ♦ Results Average peak plasma concentrations of isoniazid, rifampin, and pyrazinamide were 3.3 mg/L, 6.5 mg/L, and 30.9 mg/L, respectively, all of which much exceed the minimum inhibitory concentration (MIC) for Mycobacterium tuberculosis. Peritoneal fluid concentrations of isoniazid and pyrazinamide were maintained well above the MICs for M. tuberculosis; however, peritoneal fluid concentration of rifampin was below the therapeutic range most of the time. ♦ Conclusion For the treatment of systemic or pulmonary tuberculosis in CAPD patients, no dose adjustments are required for isoniazid, rifampin, or pyrazinamide. On the contrary, for the treatment of tuberculous peritonitis, oral rifampin therapy is not expected to be effective because of its low peritoneal fluid concentration.

Short-Dwell Cycling Intraperitoneal Cefazolin plus Ceftazidime in Peritoneal Dialysis Patients

2017 ◽  
Vol 37 (2) ◽  
pp. 218-224 ◽  
Author(s):  
Sadudee Peerapornratana ◽  
Pajaree Chariyavilaskul ◽  
Talerngsak Kanjanabuch ◽  
Kearkiat Praditpornsilpa ◽  
Somchai Eiam-Ong ◽  
...  
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Peritoneal Dialysis ◽  
High Performance ◽  
Inhibitory Concentration ◽  
Volume Overload ◽  
Plasma Samples ◽  
Dialysis Patients ◽  
Time Points ◽  
Current Guidelines

BackgroundCurrent guidelines suggest that intraperitoneal (IP) antibiotics should be administered only in a long peritoneal dialysis (PD) dwell (≥ 6 hours). The long dwell might result in low ultrafiltration and volume overload. We aim to examine plasma and dialysate concentration of cefazolin and ceftazidime after IP administration in a short-dwell (≤ 2 hours) automated cycling exchange.MethodsStable PD patients without peritonitis were invited to participate in the present study. Patients underwent 5 2-liter exchanges of PD fluid over 10 hours by the PD cycling machine without last fill or additional dwell. Cefazolin and ceftazidime (20 mg/kg each) were added to the first 5-liter bag of 2.5% dextrose PD fluid that was placed on the warmer of the PD cycling machine. Plasma samples were collected at 12 time-points over 24 hours. Dialysate samples from each exchange were also collected. Antibiotic concentrations in plasma and dialysate were then determined by high-performance liquid chromatography (HPLC).ResultsSix stable PD patients without peritonitis participated in the study. Dialysate cefazolin and ceftazidime were consistently high throughout the PD session in all patients (26 - 360 mg/L). Plasma cefazolin and ceftazidime exceeded the minimal inhibitory concentration (MIC) for susceptible organisms (≤ 8 mg/L) within 2 hours (cefazolin 28.5 ± 8.0 and ceftazidime 12.5 ± 3.4 mg/L), peak at 10 hours (51.1 ± 14.1 and 23.0 ± 5.2 mg/L) and sustained well above the MIC at 24 hours (42.0 ± 9.6 and 17.1 ± 3.1 mg/L).ConclusionsThe short-dwell cycling IP cefazolin and ceftazidime could provide adequate plasma concentration for up to 24 hours. Daily short-dwell cycling IP cefazolin and ceftazidime might be used to treat peritonitis in PD patients already using a PD cycling machine as well as selected continuous ambulatory PD (CAPD) patients who need shorter dwells during peritonitis due to increasing peritoneal solute transport.

Intraperitoneal cefazolin and ceftazidime during short-dwell exchange in peritoneal dialysis patients with peritonitis

2020 ◽  
Vol 40 (2) ◽  
pp. 179-184
Author(s):  
Pinpongsarn Triyawatanyu ◽  
Pajaree Chariyavilaskul ◽  
Weeraya Phaisal ◽  
Sadudee Peerapornratana ◽  
Talerngsak Kanjanabuch ◽  
...  
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Peritoneal Dialysis ◽  
High Performance ◽  
Plasma Concentrations ◽  
Beta Lactamase ◽  
Plasma Samples ◽  
Dialysis Patients ◽  
Target Plasma

Background: Intraperitoneal (IP) cefazolin and ceftazidime during the short-dwell (≤ 2 h) automated exchange has been shown to provide adequate dialysate and plasma concentrations for up to 24 h in peritoneal dialysis (PD) patients without peritonitis. This study aimed to evaluate plasma and dialysate concentration of this novel IP cefazolin and ceftazidime regimen during the first 24 h in PD patients with peritonitis. Methods: Cefazolin and ceftazidime (2500 mg each) were added to in to a 5-L bag containing 2.5% of dextrose PD fluid which was placed on the warmer of PD cycling machine. Patients underwent five exchanges of 2-L PD fluid over 10 h by the PD cycling machine without last fill or additional dwell. Plasma samples and dialysate samples were collected over 24 h. Cefazolin and ceftazidime concentrations in plasma and dialysate were determined by high-performance liquid chromatography. Results: Seven PD patients with peritonitis participated in this study. Plasma cefazolin and ceftazidime levels increased substantially within the first few hours, peaked around 6–10 h, and sustained well above the target plasma concentrations (10 mg L−1 for cefazolin and 16 mg L−1 for ceftazidime) until 24 h. Dialysate cefazolin and ceftazidime levels were sustained above the target peritoneal concentrations (2 mg L−1 for cefazolin and 8 mg L−1 for ceftazidime) throughout the PD session except in some samples which the antibiotics levels were unusually low, probably from beta-lactamase activity. Conclusions: IP cefazolin and ceftazidime during the short-dwell automated exchange could provide adequate dialysate and plasma concentrations in peritonitis patients. This novel regimen is a promising regimen for peritonitis in PD patients.

Pharmacokinetics of Intraperitoneal Daptomycin in Patients with Peritoneal Dialysis-Related Peritonitis

2017 ◽  
Vol 37 (1) ◽  
pp. 44-50 ◽  
Author(s):  
Laure Peyro Saint Paul ◽  
Maxence Ficheux ◽  
Danièle Debruyne ◽  
Magalie Loilier ◽  
Nicolas Bouvier ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Dwell Time ◽  
Inhibitory Concentration ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Repeated Administration ◽  
Venous Access ◽  
Time Period ◽  
Baxter Healthcare ◽  
Toxic Concentrations

BackgroundAntibiotics are preferentially delivered via the peritoneal route to treat peritoneal dialysis-related peritonitis (PDRP) to ensure that maximal concentrations are delivered to the site of infection. Our study focused on the pharmacokinetics of daptomycin (DAP) administered via the intraperitoneal (IP) route in patients with PDRP.MethodsAccording to the DaptoDP protocol (Clinical Trial No. 2012-005699-33), IP DAP was administered daily, i.e., during the 6-h Nutrineal (Baxter Healthcare Corporation, Deerfield, IL, USA) dwell time period, for 14 days, in addition to administration of the antibiotics used for the usual care of patients with PDRP. The plasma and IP levels of DAP were measured on days 1 and 5. The tested dose was 200 mg/day. The principal endpoint was the dialysate concentration after 6 hours of dwell time > 16 mg/L (corresponding to 4 x minimum inhibitory concentration [MIC] for E. faecalis).ResultsThree participants were evaluated. On day 5, the IP concentrations after 6 hours of dwell time were between 6.3 and 23.4 mg/L, and the peak plasma concentrations were between 13.0 and 15.3 mg/L.ConclusionThe results suggest that 200 mg/day is very likely sufficient for the treatment of PDRP by Staphylococci or Streptococci whereas it could be insufficient to treat PRDP by Enterococci. The good peritoneal bioavailability of DAP was quantitatively established, suggesting that IP administration could also be used as an alternate route for patients with damaged venous access. No DAP accumulation that could lead to toxic concentrations after repeated administration is expected, even in anuric patients. The protocol will further continue to assess whether a higher dose achieves the pharmacokinetic objectives.

Single-dose pharmacokinetics of orally administered terbinafine in bearded dragons (Pogona vitticeps) and the antifungal susceptibility patterns of Nannizziopsis guarroi

2021 ◽  
pp. 1-8
Author(s):  
Michael S. McEntire ◽  
Jennifer M. Reinhart ◽  
Sherry K. Cox ◽  
Krista A. Keller
Keyword(s):  
Single Dose ◽  
High Performance ◽  
Clinical Decision Making ◽  
Peak Plasma ◽  
Antifungal Susceptibility ◽  
Plasma Concentrations ◽  
Clinical Decision ◽  
Oral Solution ◽  
Susceptibility Data ◽  
Pogona Vitticeps

Abstract OBJECTIVE To identify the antifungal susceptibility of Nanniziopsis guarroi isolates and to evaluate the single-dose pharmacokinetics of orally administered terbinafine in bearded dragons. ANIMALS 8 healthy adult bearded dragons. PROCEDURES 4 isolates of N guarroi were tested for antifungal susceptibility. A compounded oral solution of terbinafine (25 mg/mL [20 mg/kg]) was given before blood (0.2 mL) was drawn from the ventral tail vein at 0, 4, 8, 12, 24, 48, 72, and 96 hours after administration. Plasma terbinafine concentrations were measured with high-performance liquid chromatography. RESULTS The antifungal minimum inhibitory concentrations against N guarroi isolates ranged from 4,000 to > 64,000 ng/mL for fluconazole, 125 to 2,000 ng/mL for itraconazole, 125 to 2,000 ng/mL for ketoconazole, 125 to 1,000 ng/mL for posaconazole, 60 to 250 ng/mL for voriconazole, and 15 to 30 ng/mL for terbinafine. The mean ± SD peak plasma terbinafine concentration in bearded dragons was 435 ± 338 ng/mL at 13 ± 4.66 hours after administration. Plasma concentrations remained > 30 ng/mL for > 24 hours in all bearded dragons and for > 48 hours in 6 of 8 bearded dragons. Mean ± SD terminal half-life following oral administration was 21.2 ± 12.40 hours. CLINICAL RELEVANCE Antifungal susceptibility data are available for use in clinical decision making. Results indicated that administration of terbinafine (20 mg/kg, PO, q 24 to 48 h) in bearded dragons may be appropriate for the treatment of dermatomycoses caused by N guarroi. Clinical studies are needed to determine the efficacy of such treatment.

scholarly journals Intravenous and Intraperitoneal Pharmacokinetics of Dalbavancin in Peritoneal Dialysis Patients

2020 ◽  
Vol 64 (5) ◽  
Author(s):  
E. T. Van Matre ◽  
I. Teitelbaum ◽  
T. H. Kiser
Keyword(s):  
Peritoneal Dialysis ◽  
Half Life ◽  
Peritoneal Fluid ◽  
Area Under The Curve ◽  
Terminal Phase ◽  
Dialysis Patients ◽  
Time Data ◽  
Open Label ◽  
Gram Positive ◽  
Clinical Pharmacokinetics

ABSTRACT Dalbavancin offers a possible treatment option for infectious peritonitis associated with peritoneal dialysis (PD) due to its coverage of Gram-positive bacteria and pharmacokinetic properties. We aimed to evaluate the clinical pharmacokinetics (PK) and pharmacodynamics of dalbavancin in a prospective, randomized, open-label, crossover PK study of adult patients with end-stage renal disease ESRD who were receiving PD. Sampling occurred prior to a single 30-min infusion of dalbavancin at 1,500 mg and at 1, 2, 3, 4, and 6 h and 7 and 14 days postadministration. Concentration-time data were analyzed via noncompartmental analysis. Pharmacodynamic parameters against common infectious peritonitis-causing pathogens were evaluated. Ten patients were enrolled. Patients were a median of 55 years old and had a median weight of 78.2 kg, 50% were female, and 70% were Caucasian. The terminal plasma half-life of dalbavancin was 181.4 ± 35.5 h. The day 0 to day 14 dalbavancin mean area under the curve (AUC) was 40,573.2 ± 9,800.3 mg·h/liter. The terminal-phase half-life of dalbavancin within the peritoneal fluid was 4.309 × 108 ± 1.140 × 109 h. The day 0 to day 14 dalbavancin mean peritoneal fluid AUC was 2,125.0 ± 1,794.3 mg·h/liter. The target plasma AUC/MIC was attained with the intravenous dose in all 10 patients for all Staphylococcus and Streptococcus species at the recommended MIC breakpoints. The intraperitoneal arm of the study was stopped early, because the first 3 patients experienced moderate to severe pain and bloating within 1 h following the administration of dalbavancin. Dalbavancin at 1,500 mg administered intravenously can be utilized without dose adjustment in peritoneal dialysis patients and will likely achieve the necessary peritoneal fluid concentrations to treat peritonitis caused by typical Gram-positive pathogens.

Phase I and Pharmacokinetic Study of the Camptothecin Analog DX-8951f Administered as a 30-Minute Infusion Every 3 Weeks in Patients With Advanced Cancer

2000 ◽  
Vol 18 (23) ◽  
pp. 3986-3992 ◽  
Author(s):  
Valérie Boige ◽  
Eric Raymond ◽  
Sandrine Faivre ◽  
Michel Gatineau ◽  
Kathleen Meely ◽  
...  
Keyword(s):  
Phase I ◽  
Intravenous Infusion ◽  
Topoisomerase I ◽  
High Performance ◽  
Plasma Concentrations ◽  
Maximum Tolerated Dose ◽  
Pharmacokinetic Analysis ◽  
Phase Ii Studies ◽  
Heavily Pretreated ◽  
Dose Limiting Toxicity

PURPOSE: DX-8951f is a totally synthetic derivative of camptothecin with greater cytotoxicity and more potent topoisomerase I inhibition than SN-38, topotecan, and camptothecin in preclinical studies. This phase I study aimed to describe the toxicity and to determine the maximum-tolerated dose (MTD) and pharmacokinetics of DX-8951f given as a 30-minute intravenous infusion every 3 weeks. PATIENTS AND METHODS: Twelve patients with refractory solid malignancies were treated with DX-8951f at dose levels ranging from 4 to 7.1 mg/m2. All but one patient had received previous chemotherapy, and eight patients were considered heavily pretreated. Total DX-8951f plasma concentrations were assayed using high-performance liquid chromatography. RESULTS: Thirty-six cycles of DX-8951f were administered. Neutropenia was the dose-limiting toxicity, and it was dose-related, reversible, and noncumulative. Other toxicities included nausea and vomiting, alopecia, asthenia, fever, and anemia. Grade 1 or 2 diarrhea was observed in seven patients but was transient and resolved without requiring treatment. Pharmacokinetic analysis showed that DX-8951f had a half-life of 7.15 hours and a clearance rate of 1.65 L/h·m2. The DX-8951f area under the plasma-concentration curve increased linearly with the dose. We defined the MTD of DX-8951f administered as a 30-minute intravenous infusion every 3 weeks as 7.1 mg/m2. CONCLUSION: The dose-limiting toxicity of DX-8951f is neutropenia. The recommended dose for phase II studies is 5.33 mg/m2 every 3 weeks in patients previously treated with chemotherapy.

Plasma and tissue pharmacokinetics of fosfomycin in morbidly obese and non-obese surgical patients: a controlled clinical trial

2019 ◽  
Vol 74 (8) ◽  
pp. 2335-2340 ◽  
Author(s):  
Christoph Dorn ◽  
David Petroff ◽  
Nancy Neumann ◽  
Alexander Kratzer ◽  
Nahed El-Najjar ◽  
...  
Keyword(s):  
Drug Exposure ◽  
Peak Plasma ◽  
Subcutaneous Tissue ◽  
Plasma Concentrations ◽  
Surgical Patients ◽  
Pharmacokinetic Analysis ◽  
Controlled Clinical Trial ◽  
Morbidly Obese ◽  
Obese Patients ◽  
Tissue Pharmacokinetics

Abstract Objectives To assess the pharmacokinetics and tissue penetration of fosfomycin in obese and non-obese surgical patients. Methods Fifteen obese patients undergoing bariatric surgery and 15 non-obese patients undergoing major intra-abdominal surgery received an intravenous single short infusion of 8 g of fosfomycin. Fosfomycin concentrations were determined by LC-MS/MS in plasma and microdialysate from subcutaneous tissue up to 8 h after dosing. The pharmacokinetic analysis was performed in plasma and interstitial fluid (ISF) by non-compartmental methods. Results Thirteen obese patients (BMI 38–50 kg/m2) and 14 non-obese patients (BMI 0–29 kg/m2) were evaluable. The pharmacokinetics of fosfomycin in obese versus non-obese patients were characterized by lower peak plasma concentrations (468 ± 139 versus 594 ± 149 mg/L, P = 0.040) and higher V (24.4 ± 6.4 versus 19.0 ± 3.1 L, P = 0.010). The differences in AUC∞ were not significant (1275 ± 477 versus 1515 ± 352 mg·h/L, P = 0.16). The peak concentrations in subcutaneous tissue were reached rapidly and declined in parallel with the plasma concentrations. The drug exposure in tissue was nearly halved in obese compared with non-obese patients (AUC∞ 1052 ± 394 versus 1929 ± 725 mg·h/L, P = 0.0010). The tissue/plasma ratio (AUCISF/AUCplasma) was 0.86 ± 0.32 versus 1.27 ± 0.34 (P = 0.0047). Conclusions Whereas the pharmacokinetics of fosfomycin in plasma of surgical patients were only marginally different between obese and non-obese patients, the drug exposure in subcutaneous tissue was significantly lower in the obese patients.

Phase I evaluation of a water-soluble etoposide prodrug, etoposide phosphate, given as a 5-minute infusion on days 1, 3, and 5 in patients with solid tumors.

1994 ◽  
Vol 12 (9) ◽  
pp. 1902-1909 ◽  
Author(s):  
D R Budman ◽  
L N Igwemezie ◽  
S Kaul ◽  
J Behr ◽  
S Lichtman ◽  
...  
Keyword(s):  
High Performance ◽  
Peak Plasma ◽  
Performance Status ◽  
Plasma Concentrations ◽  
Maximum Tolerated Dose ◽  
Water Soluble ◽  
High Dose ◽  
Maximum Plasma ◽  
Rapid Infusion ◽  
Etoposide Phosphate

PURPOSE To determine the toxicities, maximum-tolerated dose (MTD), and pharmacology of etoposide phosphate, a water-soluble etoposide derivative, administered as a 5-minute intravenous infusion on a schedule of days 1, 3, and 5 repeated every 21 days. PATIENTS AND METHODS Thirty-six solid tumor patients with a mean age of 63 years, performance status of 0 to 1, WBC count > or = 4,000/microL, and platelet count > or = 100,000/microL, with normal hepatic and renal function were studied. Doses evaluated in etoposide equivalents were 50, 75, 100, 125, 150, 175, and 200 mg/m2/d. Etoposide in plasma and urine and etoposide phosphate in plasma were measured by high-performance liquid chromatography (HPLC). Eleven of 36 patients were treated with concentrated etoposide phosphate at 150 mg/m2/d. RESULTS Grade I/II nausea, vomiting, alopecia, and fatigue were common. Leukopenia (mainly neutropenia) occurred at doses greater than 75 mg/m2, with the nadir occurring between days 15 and 19 posttreatment. All effects were reversible. Hypotension, bronchospasm, and allergic reactions were not observed in the first 25 patients. The MTD due to leukopenia was determined to be between 175 and 200 mg/m2/d. In 11 patients treated with concentrated etoposide phosphate, no local phlebitis was noted, but two patients did develop allergic phenomena. The conversion of etoposide phosphate to etoposide was not saturated in the dosages studied. Etoposide phosphate had peak plasma concentrations at 5 minutes, with a terminal half-life (t1/2) of 7 minutes. Etoposide reached peak concentrations at 7 to 8 minutes, with a t1/2 of 6 to 9 hours. Both etoposide phosphate and etoposide demonstrated dose-related linear increases in maximum plasma concentration (Cmax) and area under the curve (AUC). CONCLUSION Etoposide phosphate displays excellent patient tolerance in conventional dosages when administered as a 5-minute intravenous bolus. The suggested phase II dose is 150 mg/m2 on days 1, 3, and 5. The ability to administer etoposide phosphate as a concentrated, rapid infusion may prove of value both in the outpatient clinic and in high-dose regimens.

The disposition of TCNU (tauromustine) in human malignant glioma: pharmacokinetic studies and clinical implications

1990 ◽  
Vol 72 (5) ◽  
pp. 721-725 ◽  
Author(s):  
Ian R. Whittle ◽  
Janet S. MacPherson ◽  
J. Douglas Miller ◽  
John F. Smyth
Keyword(s):  
Malignant Glioma ◽  
High Performance ◽  
Peak Plasma ◽  
Linear Regression Analysis ◽  
Plasma Concentrations ◽  
Tissue Level ◽  
Pharmacokinetic Studies ◽  
Tissue Concentrations ◽  
Content Type ◽  
Chromatography Analysis

✓ Tauromustine (TCNU), 130 mg/sq m, was administered intraoperatively by nasogastric tube to 10 patients with malignant glioma (seven glioblastomas and three anaplastic astrocytomas). High-performance liquid chromatography analysis of 32 tumor specimens for TCNU revealed that tissue concentrations ranged from 0 to 554 ng/gm; TCNU was not detected in necrotic regions of the tumor. Levels of TCNU in brain adjacent to tumor were similar to those recorded within the gliomas (range 0 to 635 ng/gm). The variability in the tissue level of TCNU was partly attributable to variable absorption of the drug, since peak plasma TCNU levels ranged from 164 to 3333 ng/ml. There were close quantitative and temporal relationships between the times of peak plasma levels (median 456 ng/ml at 45 minutes after administration), peak tumor levels (median 250 ng/gm tissue at 55 minutes), and brain adjacent to tumor levels (median 256 ng/gm tissue at 50 minutes). Linear regression analysis of the ratio between tissue and plasma TCNU levels at particular times after drug administration suggest that plasma concentrations can be used to estimate tissue concentrations. This study demonstrates that TCNU enters malignant glioma. In view of the activity of TCNU against a range of tumors, a full clinical evaluation of this new nitrosourea in malignant glioma seems justified.

scholarly journals The influence of CYP2C8*3 on carbamazepine serum concentration in epileptic pediatric patients

2016 ◽  
Vol 19 (1) ◽  
pp. 21-28 ◽  
Author(s):  
DD Milovanovic ◽  
JR Milovanovic ◽  
M Radovanovic ◽  
I Radosavljevic ◽  
S Obradovic ◽  
...  
Keyword(s):  
Serum Concentration ◽  
High Performance ◽  
Dose Adjustment ◽  
Pediatric Patients ◽  
Plasma Concentrations ◽  
Clinical Importance ◽  
Population Pharmacokinetic Analysis ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Allele Specific

AbstractThe aim of the present study was to investigate the distribution of CYP2C8 variants *3 and *5, as well as their effect on carbamazepine pharmacokinetic properties, in 40 epileptic pediatric patients on carbamazepine treatment. Genotyping was conducted using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and allele-specific (AS)-PCR methods, and steady-state carbamazepine plasma concentrations were determined by high performance liquid chromatography (HPLC). The CYP2C8 *3 and *5 polymorphisms were found at frequencies of 17.5 and 0.0%, respectively. After dose adjustment, there was a difference in daily dose in CYP2C8*3 carriers compared to non carriers [mean ± standard deviation (SD): 14.19 ± 5.39 vs. 15.46 ± 4.35 mg/kg; p = 0.5]. Dose-normalized serum concentration of carbamazepine was higher in CYP2C8*3 (mean ± SD: 0.54 ± 0.18 vs. 0.43 ± 0.11 mg/mL, p = 0.04), and the observed correlation between weight-adjusted carbamazepine dose and carbamazepine concentration after dose adjustment was significant only in CYP2C8*3 non carriers (r = 0.52, p = 0.002). However, the population pharmacokinetic analysis failed to demonstrate any significant effect of CYP2C8 *3 polymorphism on carbamazepine clearance [CL L/h = 0.215 + 0.0696*SEX+ 0.000183*DD]. The results indicated that the CYP2C8*3 polymorphism might not be of clinical importance for epilepsy treatment in pediatric populations.

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