Association between initial diquat plasma concentration, severity index and in-hospital mortality in patients with acute diquat poisoning: a retrospective cohort study.

BACKGROUND: Since 2016, diquat has replaced paraquat in China, resulting in increased diquat poisoning cases. However, understanding of diquat poisoning is still limited. This study aimed to investigate the relationship between initial diquat plasma concentration, severity index, and in-hospital mortality in acute diquat poisoning cases. METHODS: This retrospective cohort study, conducted from January 2016 to July 2023 in a tertiary care hospital, used univariate logistic regression to examine the link between the initial diquat plasma concentration, severity index, and in-hospital mortality in acute diquat poisoned patients. A receiver operating characteristic curve assessed the predictive value of these parameters for prognosis. RESULTS: Among the 87 participants, the median age was 32 years, 35 (40.2%) were female. The overall mortality rate was 37.9%. Logistic regression analysis revealed that the initial diquat plasma concentration and severity index were associated with increased in-hospital mortality. These factors also effectively predicted the prognosis of acute diquat poisoning, with an area under the receiver operating characteristic curve of 0.851 and an optimal diquat concentration threshold of 2.25 mg/L (sensitivity 90.9%, specificity 74.1%, P < 0.05) and an area under the receiver operating characteristic curve of 0.845 with an optimal cut-off value for the sevity index of 9.1 mg/L*min (sensitivity 97%, specificity 74.1%, P < 0.05). DISCUSSION: Our results are limited by the retrospective design of this study. However, if validated, these results could impact management strategies, especially in East Asia. Further research is needed due to potential confounding factors. CONCLUSIONS: The findings suggest that a higher initial plasma concentration and severity index in patients with acute diquat poisoning were correlated with higher in-hospital mortality. Prospective validation will confirm the predicative value of these findings.

Case report: Time response of plasma clozapine concentrations on cessation of heavy smoking.

Smoking cessation in patients treated with clozapine might lead to elevated plasma concentrations and severe side effects. This case report investigated the trajectory of clozapine plasma concentrations over time after smoking cessation in a Chinese inpatient with schizophrenia. This case report delineates the temporal response of plasma clozapine concentrations and dose-corrected clozapine plasma concentrations in a 33-year-old inpatient with schizophrenia who had a substantial smoking history and ceased smoking abruptly during dose titration. This case report presents a sudden increase in plasma clozapine concentrations and dose-corrected plasma clozapine concentrations after smoking cessation, followed by a rapid decline in dose-corrected plasma clozapine concentrations during the initial 2 weeks and a return to pre-cessation levels approximately 1 month later. The findings suggest that clinicians and pharmacists should adjust clozapine dosage in accordance with changes in smoking status, taking into consideration the temporal effects. Post-smoking cessation adjustments to clozapine dosage should be coupled with therapeutic drug monitoring, especially for patients with heavy smoking habits. Moreover, the advice of the clinical pharmacist should be considered in complex cases to ensure safe use of clozapine.

Clinical Pharmacokinetics of Semaglutide: A Systematic Review.

Purpose: The aim of this review was to provide all the pharmacokinetic data for semaglutide in humans concerning its pharmacokinetics after subcutaneously and oral applications in healthy and diseased populations, to provide recommendations for clinical use. Methodology: The PubMed and Embase databases were searched to screen studies associated with the pharmacokinetics of semaglutide. The pharmacokinetic parameters included area under the curve plasma concentrations (AUC), maximal plasma concentration (Cmax), time to Cmax, half-life (t1/2), and clearance. The systematic literature search retrieved 17 articles including data on pharmacokinetic profiles after subcutaneously and oral applications of semaglutide, and at least one of the above pharmacokinetic parameter was reported in all included studies. Results: Semaglutide has a predictable pharmacokinetic profile with a long t1/2 that allows for once-weekly subcutaneous administration. The AUC and Cmax of both oral and subcutaneous semaglutide increased with dose. Food and various dosing conditions including water volume and dosing schedules can affect the oral semaglutide exposure. There are limited drug-drug interactions and no dosing adjustments in patients with upper gastrointestinal disease, renal impairment or hepatic impairment. Body weight may affect semaglutide exposure, but further studies are needed to confirm this. Conclusion: This review encompasses all the pharmacokinetic data for subcutaneous and oral semaglutide in both healthy and diseased participants. The existing pharmacokinetic data can assist in developing and evaluating pharmacokinetic models of semaglutide and will help clinicians predict semaglutide dosages. In addition, it can also help optimize future clinical trials.

Effects of CYP3A4 genetic polymorphisms on the pharmacokinetics and efficacy of perampanel in Chinese pediatric patients with epilepsy.

OBJECTIVE: This study was the first to evaluate the effect of CYP3A4 gene polymorphisms on the plasma concentration and effectiveness of perampanel (PER) in Chinese pediatric patients with epilepsy. METHODS: We enrolled 102 patients for this investigation. The steady-state concentration was determined after patients maintained a consistent PER dosing regimen for at least 21 days. Plasma PER concentrations were measured using liquid chromatography-tandem mass spectrometry. Leftover samples from standard therapeutic drug monitoring were allocated for genotyping analysis. The primary measure of efficacy was the rate of seizure reduction with PER treatment at the final check-up. RESULTS: The CYP3A4×10 GC phenotype exhibited the highest average plasma concentration of PER at 491.1 ±â€¯328.1 ng/mL, in contrast to the CC phenotype at 334.0 ±â€¯161.1 ng/mL. The incidence of adverse events was most prominent in the CYP3A4×1 G TT and CYP3A4×10 GC groups, with rates of 77.8 % (7 of 9 patients) and 50.0 % (46 of 92 patients), respectively. Moreover, the percentage of patients for whom PER was deemed ineffective was least in the CYP3A4×1 G TT and CYP3A4×10 CC groups, recorded at 11.1 % (1 of 9 patients) and 10.0 % (1 of 10 patients), respectively. There was a significant correlation between PER plasma concentration and either exposure or toxicity (both with p < 0.05). We suggest a plasma concentration range of 625-900 ng/mL as a suitable reference for PER in Chinese patients with epilepsy. CONCLUSION: The CYP3A4×10 gene's genetic polymorphisms influence plasma concentrations of PER in Chinese pediatric patients with epilepsy. Given that both efficacy and potential toxicity are closely tied to plasma PER levels, the CYP3A4 genetic phenotype should be factored in when prescribing PER to patients with epilepsy.

Paclitaxel therapeutic drug monitoring - International association of therapeutic drug monitoring and clinical toxicology recommendations.

Paclitaxel, one of the most frequently used anticancer drugs, is dosed by body surface area, which leads to substantial inter-individual variability in systemic drug exposure. We evaluated clinical evidence regarding the scientific rationale and clinical benefit of individualized paclitaxel dosing based on measured systemic concentrations, known as therapeutic drug monitoring (TDM). In retrospective studies, higher systemic exposure is associated with greater toxicity and efficacy of paclitaxel treatment across several disease types and dosing regimens. In prospective trials, TDM reduces variability in systemic exposure, and has been demonstrated to reduce toxicity while retaining treatment efficacy for 3-weekly dosing in patients with advanced non-small cell lung cancer. Despite the demonstrated benefits of paclitaxel TDM, clinical adoption has been limited due to the challenges with sample collection and analysis. Based on our review, we strongly recommend TDM for patients receiving every 3-week paclitaxel in combination with a platinum agent for advanced NSCLC, due to the prospectively demonstrated clinical benefits, and find moderate evidence to recommend TDM for paclitaxel 3-hour infusions for other tumor types and preliminary evidence suggesting potential usefulness for paclitaxel administered by 1-hour infusions.

Plasma Concentrations of Rosmarinic Acid in Patients on Antiretroviral Therapy: In Silico Exploration Based on Clinical Data.

Rosmarinic acid (RA) is a phenolic compound with antiviral properties, often encountered in dietary supplements and herbal drugs. Data on the pharmacokinetics of RA are lacking in cases of the chronic use of supplements containing this compound, and only limited data on the metabolism and distribution of RA are available. The aim of the study was to investigate the plasma levels of RA after 12 weeks of use and determine potential interactions of RA and selected antiretroviral drugs. Patients infected with human immunodeficiency virus took a supplement containing RA for 12 weeks, after which the RA concentrations in the plasma samples were analyzed. A detailed in silico analysis was conducted in order to elucidate the potential interactions between RA and the drugs efavirenz, darunavir and raltegravir. It was found that RA can be detected in patients' plasma samples, mainly in the form of sulphoglucuronide. The potential interactions are suggested on the level of liver metabolizing enzymes and efflux P-glycoprotein, with RA competing with antiretroviral drugs as a substrate in metabolism and distribution systems. The present study suggests that the simultaneous use of RA and antiretroviral therapy (containing efavirenz, darunavir or raltegravir) may affect the plasma levels of RA after prolonged supplementation.

Pilot study on the probability of drug-drug interactions among direct oral anticoagulants (DOACs) and antiseizure medications (ASMs): a clinical perspective.

BACKGROUND: There is little and controversial information about changes in plasma concentrations (PCs) or clinical events during coadministration of antiseizure medications (ASMs) and direct oral anticoagulants (DOACs). We aimed to explore possible determinants of dosage class among DOACs trough PCs when ASMs are co-administered and the relative risks. We also provided some clinical examples of patients' management. METHODS: Data on adult patients concomitantly treated with ASMs (grouped in enzyme-inducing [I-ASMs], non-inducing [nI-ASMs], and levetiracetam [LEV]) and DOACs with at least one measurement of DOACs' PC were retrospectively collected. The role of DOAC-ASM combinations in predicting PC class (ranging from I at ischemic/thromboembolic risk to IV at increased bleeding risk) was investigated by an ordered logit model, and the marginal probabilities of belonging to the four dosage classes were calculated. RESULTS: We collected 46 DOACs' PCs out of 31 patients. There were 5 (10.9%) determinations in class I (4 out of 5 with concomitant I-ASMs) and 5 (10.9%) in class IV. The rivaroxaban/I-ASM combination was associated with lower DOAC dosages than rivaroxaban/LEV (OR: 0.00; 95% CI: 0.00-0.62). Furthermore, patient's probability of being in class I was approximately 50% with the rivaroxaban/I-ASM combination, while apixaban, dabigatran, and edoxaban had the highest cumulative probability of being in class II or III despite the ASM used. CONCLUSION: These preliminary results confirm the reduction of DOAC's PC by I-ASMs and suggest a better manageability of apixaban, dabigatran, and edoxaban independently from the concomitant ASM, whereas rivaroxaban seems the most liable to PC alterations with I-ASMs.

Long-Acting Cabotegravir/Rilpivirine Concentrations in Combination With Intravenous Rifampin: A Case Report.

As antiretroviral therapy advancements focus on long-acting medications, there is a need to assess the potential impact of drug-drug interactions. We present a real-world case of long-acting cabotegravir/rilpivirine co-administered with intravenous rifampin. The combination resulted in both cabotegravir and rilpivirine concentrations falling below 4 times the protein-adjusted IC90.

Effects of smoking cessation on plasma clozapine concentrations in male patients with schizophrenia during the COVID-19 pandemic.

Introduction: This study aimed to investigate the effect of smoking cessation on plasma clozapine (CLO) concentrations in long-term hospitalized Chinese male patients with schizophrenia treated with CLO during the COVID-19 pandemic. Methods: Therapeutic drug monitoring (TDM) data for CLO were collected at Beijing HuiLongGuan Hospital between December 1, 2019 (before smoking cessation) and January 31, 2020 (after smoking cessation) in this retrospective study. Fifty-three male smokers and inpatients with schizophrenia who were treated with CLO were included. Plasma concentrations of CLO were measured using high-performance liquid chromatography-tandem mass spectrometry. The fagerstrom test for nicotine dependence (FTND) was used to assess smoking behavior. Results: The plasma CLO concentrations and dose-corrected plasma CLO concentrations were significantly increased by 29.3 and 23.5%, respectively, after smoking cessation. Discussion: The results suggested that clinicians and pharmacists should adjust the CLO dose based on changes in smoking status in patients stabilized with CLO during the COVID-19 pandemic. Careful TDM for CLO should be performed prior to dose adjustment，to reduce the increased risk of smoking cessation induced side effects, especially for older patients receiving multiple medications.

Sex-Specific Correlation Analysis of Branched-Chain Amino Acids in Dietary Intakes and Plasma among Chinese Adults.

BACKGROUND: Previous findings about the influence of dietary intakes of the branched-chain amino acid (BCAA) on their plasma concentrations have been limited and inconsistent, and evidence from the Chinese population was lacking. OBJECTIVES: This study aimed to investigate the diet-plasma BCAA correlations in Chinese male and female adults. METHODS: This cross-sectional study was based on a nested case-control study within 2 prospective population-based cohorts in Shanghai, China. Diet information was collected by the food frequency questionnaires. Plasma BCAA concentrations were measured by ultraperformance liquid chromatography coupled with tandem mass spectrometry. Spearman correlations and linear regression models were conducted to examine the relationships between dietary BCAA intakes and plasma BCAA. The multivariable model was adjusted for age at the interview, total energy intake, time of blood collection from last meal, dietary patterns, body mass index (in kg/m2), type 2 diabetes, and physical activity. RESULTS: A total of 322 males (median age of 57.0 y) and 187 females (median age of 60.0 y) were included in this cross-sectional study. The geometric means of dietary intake of leucine, isoleucine, valine, and BCAA were 4937.7, 3029.6, 3268.5, and 11237.4 mg/d in males, and 4125.7, 2567.8, 2754.3, and 9449.4 mg/d in females. The geometric means of plasma concentrations of leucine, isoleucine, valine, and BCAA were 181.9, 65.0, 219.8, and 469.4 µM/L in males and 161.6, 61.1, 206.5, and 431.6 µM/L in females. Only leucine (r = 0.1660, P = 0.0028) and total BCAA (r = 0.1348, P = 0.0155) in males exhibited weak positive correlation coefficients. After adjustment for the covariates, leucine, isoleucine, valine, and total BCAA in dietary intakes and plasma were not correlated in both males and females. CONCLUSIONS: In Chinese male and female adults, dietary intakes are not major determinants of plasma concentrations of BCAA, and plasma concentrations might not be reflected by usual dietary intakes of BCAA.

Pharmacogenomic markers of metoprolol and α-OH-metoprolol concentrations: a genome-wide association study.

Aim: Few genome-wide association studies (GWASs) have been conducted to identify predictors of drug concentrations. The authors therefore sought to discover the pharmacogenomic markers involved in metoprolol pharmacokinetics. Patients & methods: The authors performed a GWAS of a cross-sectional study of 993 patients from the Montreal Heart Institute Biobank taking metoprolol. Results: A total of 391 and 444 SNPs reached the significance threshold of 5 × 10-8 for metoprolol and α-OH-metoprolol concentrations, respectively. All were located on chromosome 22 at or near the CYP2D6 gene, encoding CYP450 2D6, metoprolol's main metabolizing enzyme. Conclusion: The results reinforce previous findings of the importance of the CYP2D6 locus for metoprolol concentrations and confirm that large biobanks can be used to identify genetic determinants of drug pharmacokinetics at a GWAS significance level.

The Associations of Habitual Intake of Sulfur Amino Acids, Proteins and Diet Quality with Plasma Sulfur Amino Acid Concentrations: The Maastricht Study.

BACKGROUND: Plasma sulfur amino acids (SAAs), i.e., methionine, total cysteine (tCys), total homocysteine (tHcy), cystathionine, total glutathione (tGSH), and taurine, are potential risk factors for obesity and cardiometabolic disorders. However, except for plasma tHcy, little is known about how dietary intake modifies plasma SAA concentrations. OBJECTIVE: To investigate whether the intake of SAAs and proteins or diet quality is associated with plasma SAAs. METHODS: Data from a cross-sectional subset of The Maastricht Study (n = 1145, 50.5% men, 61 interquartile range: [55, 66] y, 22.5% with prediabetes and 34.3% with type 2 diabetes) were investigated. Dietary intake was assessed using a validated food frequency questionnaire. The intake of SAAs (total, methionine, and cysteine) and proteins (total, animal, and plant) was estimated from the Dutch and Danish food composition tables. Diet quality was assessed using the Dutch Healthy Diet Index, the Mediterranean Diet Score, and the Dietary Approaches to Stop Hypertension score. Fasting plasma SAAs were measured by liquid chromatography (LC) tandem mass spectrometry (MS) (LC/MS-MS). Associations were investigated with multiple linear regressions with tertiles of dietary intake measures (main exposures) and z-standardized plasma SAAs (outcomes). RESULTS: Intake of total SAAs and total proteins was positively associated with plasma tCys and cystathionine. Associations were stronger in women and in those with normal body weight. Higher intake of cysteine and plant proteins was associated with lower plasma tHcy and higher cystathionine. Higher methionine intake was associated with lower plasma tGSH, whereas cysteine intake was positively associated with tGSH. Higher intake of methionine and animal proteins was associated with higher plasma taurine. Better diet quality was consistently related to lower plasma tHcy concentrations, but it was not associated with the other SAAs. CONCLUSION: Targeted dietary modifications might be effective in modifying plasma concentrations of tCys, tHcy, and cystathionine, which have been associated with obesity and cardiometabolic disorders.

Should Airway Interstitial Fluid Be Used to Evaluate the Pharmacokinetics of Macrolide Antibiotics for Dose Regimen Determination in Respiratory Infection?

Macrolide antibiotics are important drugs to combat infections. The pharmacokinetics (PK) of these drugs are essential for the determination of their optimal dose regimens, which affect antimicrobial pharmacodynamics and treatment success. For most drugs, the measurement of their concentrations in plasma/serum is the surrogate for drug concentrations in target tissues for therapy. However, for macrolides, simple reliance on total or free drug concentrations in serum/plasma might be misleading. The macrolide antibiotic concentrations of serum/plasma, interstitial fluid (ISF), and target tissue itself usually yield very different PK results. In fact, the PK of a macrolide antibiotic based on serum/plasma concentrations alone is not an ideal predictor for the in vivo efficacy against respiratory pathogens. Instead, the PK based on drug concentrations at the site of infection or ISF provide much more clinically relevant information than serum/plasma concentrations. This review aims to summarize and compare/discuss the use of drug concentrations of serum/plasma, airway ISF, and tissues for computing the PK of macrolides. A better understanding of the PK of macrolide antibiotics based on airway ISF concentrations will help optimize the antibacterial dose regimen as well as minimizing toxicity and the emergence of drug resistance in clinical practice.

Effects of UGT1A, CYP2C9/19 and ABAT polymorphisms on plasma concentration of valproic acid in Chinese epilepsy patients.

Aim: To evaluate the association between genetic polymorphisms and plasma concentration-to-dose ratio of valproic acid (CDRV) in Chinese epileptic patients. Methods: A total of 46 epileptic patients treated with valproic acid therapy were enrolled. 18 SNPs in nine genes related to valproic acid were directly sequenced with Sanger methods. Results: Patients carrying UGT1A6 heterozygous genotypes had significantly lower CDRV than those carrying the wild-type genotypes. In contrast, patients with the homozygote genotypes of CYP2C9 and ABAT had higher CDRV than those with the wild-type genotypes and patients with the heterozygous genotypes of CYP2C19 had higher CDRV. Conclusion: Detection of genetic polymorphism in these genes might facilitate an appropriate dose of valproic acid for epileptic patients. Further studies with larger cohorts are necessary to underpin these observations.

Association of CYP2C19, CYP3A4 and ABCC2 polymorphisms and voriconazole plasma concentrations in Uygur pediatric patients.

Aim: To evaluate the association between CYP2C19, CYP3A4 and ABCC2 polymorphisms and voriconazole plasma concentrations in Uygur pediatric patients with allogeneic hematopoietic stem cell transplantation. Materials & methods: High performance liquid chromatography-mass spectrometry was employed to monitor voriconazole concentrations. First-generation sequencing was performed to detect gene polymorphisms. Results: Voriconazole concentrations of normal metabolizers were significantly higher than those of intermediate (p < 0.05) and ultrafast (p < 0.001) metabolizers. Patients with ABCC2 GG and GA genotypes exhibited significantly lower voriconazole concentrations compared with patients with the AA genotype (p < 0.05). Conclusion: These results demonstrate a significant association between voriconazole concentrations and the CYP2C19 phenotype in Uygur pediatric patients with allogeneic hematopoietic stem cell transplantation.

Imatinib plasma levels in patients with gastrointestinal stromal tumour under routine clinical practice conditions.

OBJECTIVES: Imatinib is the first therapeutic option for the treatment of unresectable or metastatic gastrointestinal stromal tumours. Previous studies have shown an improvement in patient survival rates following the use of imatinib. Nevertheless, adequate plasma concentrations of imatinib are necessary to achieve such improvement in survival and limit the toxicity of the drug. This study aims to analyse the influence of imatinib plasma concentrations on efficacy and safety in the treatment of gastrointestinal stromal tumour. MATERIALS AND METHODS: This descriptive, multicentre study analysed plasma levels of imatinib in patients diagnosed with gastrointestinal stromal tumour in the period 2019-2020. An optimal therapeutic range of 750-1500 ng/mL was established for the patient stratification based on their minimum plasma concentrations measured at the steady state. RESULTS: This study included 11 patients with metastatic disease in total, among whom only 54.5% (n = 6) had a minimum plasma concentrations measured at the steady state value within the therapeutic range. A median progression-free survival of 7.0 months was recorded for those patients with minimum plasma concentrations measured at the steady state < 750 ng/mL, while that median progression-free survival value remained unachieved for the group with minimum plasma concentrations measured at the steady state > 750 ng/mL (p = 0.005). The toxicity rate was 25% and 14.3% for patients with minimum plasma concentrations measured at the steady state > 1500 ng/mL and minimum plasma concentrations measured at the steady state ≤1500 ng/mL, respectively (p = 0.66). CONCLUSIONS: The present study aims to describe the correlation between the toxicity and effectiveness of imatinib as a function of minimum plasma concentrations measured at the steady state under routine clinical practice conditions. The results described here show the usefulness of imatinib plasma concentrations monitoring as part of the standard daily routine in our hospitals.

Imatinib plasma levels in patients with chronic myeloid leukaemia under routine clinical practice conditions.

INTRODUCTION: The addition of imatinib to the therapeutic arsenal for chronic myeloid leukaemia (CML) has changed the natural course of the disease, in such a way that it is now considered a chronic pathology. However, to achieve therapeutic success, it is necessary to reach adequate plasma concentrations to ensure efficacy and safety.In this study, we aimed to evaluate the plasma concentration of imatinib, analysing its influence on effectiveness and safety in patients with CML. METHODS: We performed a descriptive, multicentre study in which imatinib plasma levels from patients diagnosed with CML between 2019-2020 were analysed. An optimal therapeutic range of 750-1500 ng/mL was established for the stratification of patients, according to their minimum plasma concentrations measured at steady state (Cssmin). RESULTS: A total of 28 patients were included, of whom only 39.3% (n = 11) showed Cssmin within the therapeutic range. 100% of patients with Cssmin >750 ng/mL achieved an optimal molecular response, while only 50% of patients with Cssmin <750 ng/mL achieved an optimal molecular response (p = 0.0004). The toxicity rate was 36.4% for patients with Cssmin >1500 ng/mL and 5.9% for those with Cssmin <1500 ng/mL (p = 0.039). CONCLUSIONS: This study aimed to describe the correlation between the toxicity and effectiveness of imatinib according to its Cssmin in routine clinical practice conditions. Based on our findings, it would be certainly justified to monitor patient plasma concentrations of imatinib on a daily routine basis in our hospitals.

Fluctuating Voriconazole Concentrations during Extracorporeal Membrane Oxygenation.

BackgroundPatients requiring extracorporeal membrane oxygenation (ECMO) demonstrate complex drug pharmacokinetics due to alterations in clearance and volume of distribution, necessitating close therapeutic drug monitoring. Case Report: A 19-year-old Caucasian female with no past medical history was transferred from an outside hospital and admitted to the intensive care unit for acute respiratory distress syndrome secondary to a fresh water drowning event. The patient decompensated, requiring veno-arterial ECMO, which was subsequently changed to veno-venous ECMO. She was diagnosed with a Scedosporium apiospermum fungal pneumonia and was started on voriconazole. Throughout the course of antifungal therapy, the patient's voriconazole concentrations were labile, ranging from subtherapeutic, requiring dose increases to twice the labeled therapeutic dose, followed by subsequent supratherapeutic concentrations, requiring dose reductions. Conclusion: Our findings demonstrate how voriconazole drug concentrations can be unpredictable when administered during ECMO and the importance of close monitoring of drug concentrations. More studies are needed to provide sufficient guidance on administering voriconazole in critically ill patients receiving ECMO.

Medication with fenbendazole in feed: plasma concentrations and effects on hepatic xenobiotic metabolizing enzymes in swine.

Fenbendazole (FBZ), a benzymidazole (BZD) anthelmintic drug, is used for in-feed medication in pigs. BZD-containing drugs may induce cytochrome P450 isozymes (CYPs), particularly those members of the CYP1A subfamily. The current research evaluated the plasma and liver availability and metabolism of FBZ and its metabolites, oxfendazole (OFZ) and fenbendazole sulphone (FBZSO2), after the administration of the parent drug in feed, and characterized the effect of the sustained administration of the anthelmintic on the catalytic activities of xenobiotic metabolizing enzymes in pig liver. Five female Landrace piglets remained untreated (controls), and other six were treated with a pre-mix of FBZ, combined with feed, for 9 consecutive days as usually is recommended. Blood samples were collected from each treated animal up to day 9 and analyzed by HPLC; all animals were slaughtered for preparation of liver microsomes. Plasma concentration ratios OFZ/FBZ and FBZSO2/OFZ increased significantly (p < 0.05) from the beginning to the end of drug exposure, which may indicate an enhanced conversion of FBZ into its metabolites. FBZ represented 45.8 ± 3.4% of the total anthelmintic molecules in liver tissue. Increased CYP1A-dependent 7-ethoxy (24.5-fold, p = 0.0032) and 7-methoxyresorufin (17.2-fold, p = 0.0006) O-dealkylase activities was observed in liver microsomes from FBZ-treated animals. In addition, a 64% increase (p = 0.042) in the rate of FBZ S-oxidation was observed in pigs treated with the anthelmintic drug compared to that measured in untreated animals. Thus, the continuous FBZ administration may accelerate its own in vivo hepatic metabolism through the CYP1A pathway.