Therapeutic Drug Monitoring最新文献

{"title":"Liquid Chromatography-Tandem Mass Spectrometry Method for Therapeutic Drug Monitoring of Dalbavancin in Plasma of Pediatric and Young Adult Patients.","authors":"Alessia Cafaro, Marcello Mariani, Federica Pigliasco, Giammarco Baiardi, Sebastiano Barco, Margherita Biondi, Alessio Mesini, Chiara Russo, Carolina Saffioti, Francesca Mattioli, Elio Castagnola, Giuliana Cangemi","doi":"10.1097/FTD.0000000000001260","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001260","url":null,"abstract":"<p><strong>Background: </strong>Dalbavancin, an antimicrobial lipoglycopeptide, is authorized in Europe for treating acute bacterial infections of the skin and skin structures in adults and pediatric patients aged 3 months and older. However, off-label dosing regimens have been proposed for various indications beyond acute bacterial infections of the skin and skin structures. This study presents a novel bioanalytical method using liquid chromatography-tandem mass spectrometry to quantify dalbavancin in low-volume plasma samples (50 μL).</p><p><strong>Methods: </strong>The method underwent validation in accordance with international guidelines for bioanalytical method validation and was applied to 9 clinical samples obtained from pediatric and young adult patients undergoing dalbavancin therapy. Liquid chromatography-tandem mass spectrometry analyses were conducted at the G. Gaslini Institute in Genoa, Italy, utilizing an Ultimate 3000 ultra high performance liquid chromatography system coupled to a TSQ Quantiva Triple Quadrupole system (Thermo Fisher Scientific, Milan, Italy). The analytical procedure involved the addition of deuterated dalbavancin as internal standard and a rapid extraction from 50 µL of human plasma, followed by chromatographic separation on a Thermo Scientific Accucore Polar Premium column. Accurate quantification of the analyte was achieved through multiple reaction monitoring detection.</p><p><strong>Results: </strong>The assay exhibited linearity within the concentration range of 0.66-400 mcg/mL in plasma, demonstrating accuracy and reproducibility in the absence of matrix effects. Stability testing was conducted on both quality controls and real samples to establish a robust protocol under real-life conditions.</p><p><strong>Conclusions: </strong>This fast and reliable dalbavancin quantitation method could improve current pediatric clinical practice by enabling data collection for future dose recommendations in special patient populations.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Switching Vancomycin Monitoring From Trough Concentration to Area Under the Curve Estimation by Bayesian Forecasting: A Short Communication on a Cost-Benefit Study in Resource-Limited Settings.","authors":"João Paulo Telles, Diogenes Coelho, Karen Cristina Migotto, Mariana Suelotto Diegues, Erica Rocha Leao, Rodrigo Reghini, Natalia Martinez Martos, Pedro Caruso, Ivan Leonardo França E Silva","doi":"10.1097/FTD.0000000000001223","DOIUrl":"10.1097/FTD.0000000000001223","url":null,"abstract":"<p><strong>Background: </strong>This study was conducted to evaluate the cost-benefit indicators of a vancomycin monitoring protocol based on area under the curve estimation using commercial Bayesian software.</p><p><strong>Methods: </strong>This quasi-experimental study included patients who were aged >18 years with a vancomycin prescription for >24 hours. Patients who were terminally ill or those with acute kidney injury (AKI) ≤24 hours were excluded. During the preintervention period, doses were adjusted based on the trough concentration target of 15-20 mg/L, whereas the postintervention period target was 400-500 mg × h/L for the area under the curve. The medical team was responsible for deciding to stop the antimicrobial prescription without influence from the therapeutic drug monitoring team. The main outcomes were the incidence of AKI and length of stay. Cost-benefit simulation was performed after statistical analysis.</p><p><strong>Results: </strong>There were 96 patients in the preintervention group and 110 in the postintervention group. The AKI rate decreased from 20% (n = 19) to 6% (n = 6; P = 0.003), whereas the number of vancomycin serum samples decreased from 5 (interquartile range: 2-7) to 2 (interquartile range: 1-3) examinations per patient ( P < 0.001). The mean length of hospital stay for patients was 26.19 days after vancomycin prescription, compared with 17.13 days for those without AKI ( P = 0.003). At our institution, the decrease in AKI rate and reduced length of stay boosted yearly savings of up to US$ 369,000 for 300 patients receiving vancomycin therapy.</p><p><strong>Conclusions: </strong>Even in resource-limited settings, a commercial Bayesian forecasting-based protocol for vancomycin is important for determining cost-benefit outcomes.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"681-686"},"PeriodicalIF":2.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141535345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Personalized Amoxicillin Therapy in a Critically Ill Patient Undergoing Renal Replacement Therapy: A Grand Round.","authors":"Philippine Garrigue, Margot Reber, Sophie Perinel-Ragey, Manon Launay","doi":"10.1097/FTD.0000000000001242","DOIUrl":"10.1097/FTD.0000000000001242","url":null,"abstract":"<p><strong>Background: </strong>The case study discusses a complex scenario involving the use of amoxicillin in a critically ill patient undergoing intermittent renal replacement therapy.Severe infections are complicated by septic shock and organ failure, requiring urgent and effective antibiotic treatment.</p><p><strong>Methods: </strong>The patient's comorbidities, including obesity and acute kidney injury, required careful consideration of the amoxicillin dosing strategies.</p><p><strong>Results: </strong>Therapeutic drug monitoring is critical for dose adjustment during treatment.</p><p><strong>Conclusions: </strong>This case highlights the importance of a collaborative approach between clinicians and therapeutic drug monitoring consultants to optimize antibiotic therapy for critically ill patients with renal impairment.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"559-562"},"PeriodicalIF":2.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simultaneous Determination of Ibrutinib, Dihydroxydiol Ibrutinib, and Zanubrutinib in Human Plasma by Liquid Chromatography-Mass Spectrometry/Mass Spectrometry.","authors":"Yu-Jiao Guo, Tian-Tian Du, Yan-Ling Yang, Yang Zhao, Xiang-Long Chen, Hong Ma, Lu-Ning Sun, Yong-Qing Wang","doi":"10.1097/FTD.0000000000001190","DOIUrl":"10.1097/FTD.0000000000001190","url":null,"abstract":"<p><strong>Background: </strong>Ibrutinib and zanubrutinib are Bruton tyrosine kinase inhibitors used to treat mantle cell lymphoma, chronic lymphocytic leukemia, and small lymphocytic lymphoma. Dihydroxydiol ibrutinib (DHI) is an active metabolite of the drug. A liquid chromatography-tandem mass spectrometry method was developed to detect ibrutinib, DHI, and zanubrutinib in human plasma.</p><p><strong>Methods: </strong>The method involved a protein precipitation step, followed by chromatographic separation using a gradient of 10 mM ammonium acetate (containing 0.1% formic acid)-acetonitrile. Ibrutinib-d5 was used as an internal standard. Analytes were separated within 6.5 minutes. The optimized multiple reaction monitoring transitions of m/z 441.1 → 304.2, 475.2 → 304.2, 472.2 → 455.2, and 446.2 → 309.2 were selected to inspect ibrutinib, DHI, zanubrutinib, and the internal standards in positive ion mode.</p><p><strong>Results: </strong>The validated curve ranges included 0.200-800, 0.500-500, and 1.00-1000 ng/mL for ibrutinib, DHI, and zanubrutinib, respectively. The precisions of the lower limit of quantification of samples were below 15.5%, the precisions of the other level samples were below 11.4%, and the accuracies were between -8.6% and 8.4%. The matrix effect and extraction recovery of all compounds ranged between 97.6%-109.0% and 93.9%-105.2%, respectively. The selectivity, accuracy, precision, matrix effect, and extraction recovery results were acceptable according to international method validation guidelines.</p><p><strong>Conclusions: </strong>A simple and rapid method was developed and validated in this study. This method was used to analyze plasma concentrations of ibrutinib and zanubrutinib in patients with mantle cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, or diffuse large B-cell lymphoma. The selected patients were aged between 44 and 74 years.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"634-641"},"PeriodicalIF":2.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140294642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unpredictable Cyclosporine Clearance in a Korean Patient With Aplastic Anemia With Adverse Effects: A Case Study.","authors":"Renata Shihmanter, Edward B Miller, Ekaterina Shvartsman, Haim Shmuely","doi":"10.1097/FTD.0000000000001244","DOIUrl":"10.1097/FTD.0000000000001244","url":null,"abstract":"<p><strong>Abstract: </strong>A 29-year-old Korean woman with chronic aplastic anemia presented with seizures due to cyclosporine-induced posterior reversible encephalopathy syndrome, caused by unpredictable oral cyclosporine (CS) accumulation and prolonged elimination. This case demonstrates the need to monitor CS drug levels with careful dose adjustments.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"563-566"},"PeriodicalIF":2.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Predictive Equation for the Estimation of Plasma Concentrations of Formed Colistin in Patients Treated With Colistimethate Sodium for Multidrug-Resistant Gram-Negative Bacterial Infections.","authors":"Sonia Luque, Luisa Sorlí, Jian Li, Xènia Fernández-Sala, Nuria Berenguer, Elena Colominas-González, Adela Benítez-Cano, María Milagro Montero, Isaac Subirana, Nuria Prim, Ramón García-Paricio, Juan Pablo Horcajada, Santiago Grau","doi":"10.1097/FTD.0000000000001216","DOIUrl":"10.1097/FTD.0000000000001216","url":null,"abstract":"<p><strong>Background: </strong>The clinical use of colistin methanesulphonate (CMS) is limited by potential nephrotoxicity. The selection of an efficient and safe CMS dose for individual patients is complicated by the narrow therapeutic window and high interpatient pharmacokinetic variability. In this study, a simple predictive equation for estimating the plasma concentration of formed colistin in patients with multidrug and extremely drug-resistant gram-negative bacterial infections was developed.</p><p><strong>Methods: </strong>The equation was derived from the largest clinical cohort of patients undergoing therapeutic drug monitoring (TDM) of colistin for over 8 years in a tertiary Spanish hospital. All variables associated with C ss,avg were selected in a multiple linear regression model that was validated in a second cohort of 40 patients. Measured C ss,avg values were compared with those predicted by our model and a previous published algorithm for critically ill patients.</p><p><strong>Results: </strong>In total, 276 patients were enrolled [the mean age was 67.2 (13.7) years, 203 (73.6%)] were male, and the mean (SD) C ss,avg was 1.12 (0.98) mg/L. Age, gender, estimated glomerular filtration rate, CMS dose and frequency, and concomitant drugs were included in the model. In the external validation, the previous algorithm appeared to yield more optimized colistin plasma concentrations when all types of C ss,avg values (high and low) were considered, while our equation yielded a more optimized prediction in the subgroup of patients with low colistin plasma concentrations (C ss,avg <1.5 mg/L).</p><p><strong>Conclusions: </strong>The proposed equation may help clinicians to better use CMS among a wide variety of patients, to maximize efficacy and prevent nephrotoxicity. A further prospective PK study is warranted to externally validate this algorithm.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"594-602"},"PeriodicalIF":2.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141564427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population Pharmacokinetics and Limited Sampling Strategy of Mycophenolate Mofetil for Indian Patients With Lupus Nephritis.","authors":"Kévin Koloskoff, Ritika Panwar, Manish Rathi, Sumith Mathew, Aman Sharma, Pierre Marquet, Sylvain Benito, Jean-Baptiste Woillard, Smita Pattanaik","doi":"10.1097/FTD.0000000000001213","DOIUrl":"10.1097/FTD.0000000000001213","url":null,"abstract":"<p><strong>Background: </strong>Mycophenolic acid is widely used to treat lupus nephritis (LN). However, it exhibits complex pharmacokinetics with large interindividual variability. This study aimed to develop a population pharmacokinetic (popPK) model and a 3-sample limited sampling strategy (LSS) to optimize therapeutic drug monitoring in Indian patients with LN.</p><p><strong>Methods: </strong>Five blood samples from each LN patient treated with mycophenolic acid were collected at steady-state predose and 1, 2, 4, and 6 hours postdose. Demographic parameters were tested as covariates to explain interindividual variability. PopPK analysis was performed using Monolix and the stochastic approximation expectation-maximization algorithm. An LSS was derived from 500 simulated pharmacokinetic (PK) profiles using maximum a posteriori Bayesian estimation to estimate individual PK parameters and area under the curve (AUC). The LSS-calculated AUC was compared with the AUC calculated using the trapezoidal rule and all the simulated samples.</p><p><strong>Results: </strong>A total of 51 patients were included in this study. Based on the 245 mycophenolic acid concentrations, a 1-compartmental model with double absorption using gamma distributions best fitted the data. None of the covariates improved the model significantly. The model was internally validated using diagnostic plots, prediction-corrected visual predictive checks, and bootstrapping. The best LSS included samples at 1, 2, and 4 hours postdose and exhibited good performances in an external dataset (root mean squared error, 21.9%; mean bias, -4.20%).</p><p><strong>Conclusions: </strong>The popPK model developed in this study adequately estimated the PK of mycophenolic acid in adult Indian patients with LN. This simple LSS can optimize TDM based on the AUC in routine practice.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"567-574"},"PeriodicalIF":2.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population Pharmacokinetic Modeling of Unbound Meropenem in Patients Undergoing Continuous Renal Replacement Therapy: An Observational Cohort Study.","authors":"Kazutaka Oda, Hirofumi Jono, Hidenobu Kamohara, Hideyuki Saito","doi":"10.1097/FTD.0000000000001222","DOIUrl":"10.1097/FTD.0000000000001222","url":null,"abstract":"<p><strong>Background: </strong>The most effective dosing strategy of meropenem for patients undergoing continuous renal replacement therapy (CRRT) remains uncertain. This study aimed to analyze the population pharmacokinetics (popPKs) of unbound meropenem and establish an appropriate dosing approach.</p><p><strong>Methods: </strong>This prospective study involved 19 patients for the development of a popPK model and an additional 10 for its validation. Ethical approval was obtained.</p><p><strong>Results: </strong>The clearance of unbound meropenem was influenced by the sequential organ failure assessment (SOFA) score [=2.22 × (SOFA score/12)^1.88] and the effluent flow rate from the CRRT device, with an interindividual variability of 44.5%. The volume of distribution was affected by the simplified acute physiology score II [=23.1 × (simplified acute physiology score II/52)^1.54]. Monte Carlo simulations suggested meropenem doses ranging from 1.0 to 3.0 g/d using continuous infusion to achieve a target time above the 4 times of minimum inhibitory concentration of the unbound form (% f T >4×MIC ) of 100% for definitive therapy. For empirical therapy, a dose of 1.0 g/d using continuous infusion was recommended to target % f T >MIC of 100%.</p><p><strong>Conclusions: </strong>This study developed a popPK model for unbound meropenem in patients undergoing CRRT and formulated dosing guidelines.</p><p><strong>Clinical trial registration: </strong>UMIN000024321.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"584-593"},"PeriodicalIF":2.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140959642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Validation of a High-Performance Liquid Chromatography With Ultraviolet Detection Method to Facilitate Therapeutic Monitoring of Teicoplanin Using Dried Blood Spots.","authors":"Ola Ramadan, Patrick Opitz, Georg Hempel","doi":"10.1097/FTD.0000000000001202","DOIUrl":"10.1097/FTD.0000000000001202","url":null,"abstract":"<p><strong>Background: </strong>In neonatal and pediatric intensive care units, Gram -positive infections are a significant cause of morbidity and mortality. The increase in infections caused by methicillin-resistant Staphylococcus aureus and methicillin-resistant coagulase-negative Staphylococci have led to the increased use of glycopeptides, which treat invasive infections caused by Gram -positive organisms, particularly those resistant to beta-lactam antibiotics. Teicoplanin has bacteriostatic activity against Gram -positive bacteria, but its pharmacokinetics in children is highly variable, with most children failing to reach target levels at the recommended dose. This study aimed to develop a cost-effective method for determining concentrations using dried blood spot (DBS).</p><p><strong>Methods: </strong>A method to determine the concentrations of teicoplanin in 20 µL blood or plasma using the Whatman 903 Protein Saver filter was evaluated. High-performance liquid chromatography with ultraviolet detection high-performance liquid chromatography with ultraviolet/vis was used, with internal standard ketoconazole. In addition, a method to quantify teicoplanin using 50 µL of liquid plasma was established to compare the results with the values obtained by DBS and dried plasma methods.</p><p><strong>Results: </strong>The method was successfully developed and validated for 20 µL DBS. Furthermore, 50 µL of plasma was used to quantify teicoplanin with a lower limit of quantification of 10 mg/L. Precision and accuracy ranged from 2.3% to 10.7% and 95%-114.2%, respectively. A consistent factor (1.15) was used to calculate teicoplanin plasma concentrations from whole blood, indicating the reliability of the DBS method for therapeutic drug monitoring of teicoplanin.</p><p><strong>Conclusions: </strong>A simple, reliable, and cost-effective method using high-performance liquid chromatography with ultraviolet/vis was established to determine pediatric teicoplanin concentrations in both small plasma sample volumes and whole blood using DBS, and an accurate correlation factor for estimating teicoplanin plasma concentrations from DBS was identified. This method is suitable for the use in pediatrics.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"627-633"},"PeriodicalIF":2.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141451622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dose Estimation Utility in a Population Pharmacokinetic Analysis of Inhaled Δ9-Tetrahydrocannabinol Cannabis Market Products in Occasional and Daily Users.","authors":"Thomas K Henthorn, George S Wang, Greg Dooley, Ashley Brooks-Russell, Julia Wrobel, Sarah Limbacher, Michael Kosnett","doi":"10.1097/FTD.0000000000001224","DOIUrl":"10.1097/FTD.0000000000001224","url":null,"abstract":"<p><strong>Background: </strong>Unusually high variability in blood Δ9-tetrahydrocannabinol (THC) concentrations have been observed in subjects inhaling similar cannabis products over similar time periods when consumption is ad libitum. This makes simple gravimetric dose estimation a poor predictor of THC exposure. Population pharmacokinetic analyses of blood THC concentration versus time data are routinely used to estimate pharmacokinetic parameters. The aim of this study was to estimate the inhaled dose of THC in occasional and daily users of high potency market cannabis.</p><p><strong>Methods: </strong>Blood THC concentrations were measured for 135 minutes from 29 participants who either smoked high concentration flower or inhaled concentrates ad libitum during a 15-minute session. Frequent blood samples were obtained over the following 135 minutes.</p><p><strong>Results: </strong>The estimated central and rapidly equilibrating volumes of distribution of a 3-compartment model were 19.9 ± 1.2 and 51.6 ± 4.7 L whereas the intercompartmental clearances were 1.65 ± 0.14 and 1.75 ± 0.10 L/min, respectively. Covariate-adjusted analysis revealed that the estimated inhaled THC dose was considerably less among occasional users compared with daily users.</p><p><strong>Conclusions: </strong>Three-compartment pharmacokinetics of THC did not differ among the 3 user groups, and the early phase (first 135 minutes postinception of inhalation) kinetics were similar to those previously described after smoking low potency cannabis products. Therefore, inhaled THC dose can be estimated from pharmacokinetic data and covariate-driven adjustments can be used to estimate THC doses, based on the participant cannabis usage pattern (occasional versus daily), improving the accuracy of THC exposure estimates compared with those derived from weighed THC content alone.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":"672-680"},"PeriodicalIF":2.8,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11389879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}