Accurate drug concentration measurement is essential for precision pharmacotherapy, but conventional therapeutic drug monitoring (TDM) requires venous sampling, increasing patient burden, and potentially limiting participation in TDM and model-informed precision dosing (MIPD). Volumetric microsampling enables self-collection of small, fixed volume capillary samples for centralized analysis and may reduce hematocrit-related volumetric bias associated with conventional dried blood spots. This scoping review, conducted according to the PRISMA Extension for Scoping Reviews, synthesized 67 patient-cohort studies published from 2014 through 2026. Studies spanned at least 18 countries and multiple clinical specialties. Liquid chromatography-tandem mass spectrometry was used in 61 studies (91%), and most reported validation using or referencing EMA, FDA, IATDMCT, or CLSI criteria. Recovery was minimally affected across evaluated hematocrit ranges for most analytes, and many analytes remained stable in dried samples, although stability varied by analyte and storage conditions. Where assessed, patient preference was high (80%-100%). However, interpretation against established plasma therapeutic ranges often required whole-blood-to-plasma or capillary-to-venous conversion, with inconsistent derivation and validation methods. Fixed conversion factors performed well for lacosamide and levetiracetam but were less reliable for lamotrigine at high concentrations. Several analyte-matrix combinations, including cefepime, vancomycin, meropenem, paclitaxel, abiraterone, and mitotane, did not consistently meet agreement criteria. Volumetric microsampling can support patient-centered drug monitoring when validated for the specific analyte, matrix, device, and clinical application. Future research should prioritize drug-specific optimization, multicenter validation, standardized conversion reporting, and integration with MIPD platforms.
Gotistobart is an investigational, next-generation, humanized IgG1 monoclonal antibody targeting cytotoxic T-lymphocyte antigen-4. It is engineered to preserve cytotoxic T-lymphocyte antigen-4 through endosomal recycling while enhancing intratumoral regulatory T-cell depletion. A population pharmacokinetic model was developed to characterize gotistobart pharmacokinetics and identify covariates contributing to inter-individual variability in patients with advanced solid tumors. Serum concentration-time data were obtained from 632 patients enrolled in three phase I-III clinical trials. In total, 3406 pharmacokinetic observations across a dose range from 0.1 to 10 mg/kg were collected. A two-compartment model with linear elimination best described the data, with inter-individual variability on clearance, central volume, and peripheral volume. Parameter estimates were precise, with typical values of 0.005 L/h for clearance, 0.021 L/h for inter-compartmental clearance, 2.59 L for central volume, and 3.43 L for peripheral volume. Covariates identified in the model included body weight and albumin on clearance and volumes, and sex on volumes, with limited clinically relevant impact. The model was evaluated using parameter precision, goodness-of-fit diagnostics, and prediction-corrected visual predictive checks. The model was used to simulate concentration-time profiles for clinically relevant dosing regimens. Simulations demonstrated the expected steady-state pharmacokinetic behavior, with dose-dependent increases in peak and trough concentrations. Compared with 6 mg/kg every 3 weeks, administration of two 10 mg/kg loading doses followed by 6 mg/kg every 3 weeks accelerated the attainment of steady state. The validated population pharmacokinetic model provides a quantitative foundation for subsequent exposure-response analyses and regimen selection.
Cisgender women face an increased risk of HIV acquisition during pregnancy and postpartum. Oral pre-exposure prophylaxis (PrEP) with emtricitabine and tenofovir disoproxil fumarate (F/TDF) is recommended in pregnancy despite limited published pharmacokinetic (PK) and efficacy data during pregnancy. Altered PK during pregnancy may reduce prophylactic efficacy and necessitate higher adherence. Tenofovir alafenamide (TAF) is a newer tenofovir prodrug with higher tenofovir diphosphate (TFV-DP) exposure in peripheral blood mononuclear cells (PBMCs), but the prophylactic efficacy of F/TAF across different reproductive stages in women is understudied. We adapted a multiscale modeling framework to predict the prophylactic efficacy of F/TDF and F/TAF across varying adherence levels and during the second trimester, third trimester, and 6-12 weeks postpartum. Clinical trial simulations were conducted utilizing PBMC TFV-DP and emtricitabine triphosphate concentrations as surrogate markers for F/TAF and F/TDF efficacy. For both F/TDF and F/TAF, prophylactic efficacy was lowest during the second trimester, increased in the third trimester (but remained below nonpregnant levels), and was highest postpartum. At high adherence levels of five or more pills per week, predicted effectiveness remained high across pregnancy and postpartum and effectiveness exceeded 97% for both regimens, with maximum decreases in the second trimester of only 0.9 percent point for F/TDF and 0.3 percent point for F/TAF. These findings suggest that adherence is the primary determinant of PrEP effectiveness during pregnancy and postpartum, while pregnancy-related PK changes have a limited impact on efficacy.
Balcinrenone (AZD9977) is a novel selective non-steroidal mineralocorticoid receptor antagonist with a distinct mode of action being developed as a fixed-dose combination with the sodium-glucose cotransporter-2 inhibitor dapagliflozin for the treatment of heart failure with impaired kidney function, and chronic kidney disease. In this Phase 1 randomized open-label three-way crossover study we investigated the effect of food on balcinrenone/dapagliflozin pharmacokinetics, and the pharmacokinetics of balcinrenone when dosed with a P-glycoprotein (P-gp) inhibitor. Fourteen healthy participants were administered an oral capsule of balcinrenone/dapagliflozin 40 mg/10 mg in three dosing periods: fasted (reference), fed (high-fat, high-calorie meal) and with a P-gp inhibitor (quinidine 300 mg × 2). Balcinrenone exposure was comparable in the fed and fasted states (geometric mean ratios [GMRs] [90% CI]: maximum plasma concentration [Cmax] 1.05 [0.88, 1.25]; area under the plasma concentration-time curve from time 0 to infinity [AUCinf] 1.12 [1.06, 1.19]). In the fed state, dapagliflozin AUCinf was comparable to the fasted state (GMR [90% CI] 1.05 [1.01, 1.09]), whereas Cmax was decreased (GMR [90% CI] 0.59 [0.51, 0.69]), in line with previous dapagliflozin food interaction studies. Co-administration with quinidine increased balcinrenone exposure: GMRs (90% CI) 1.48 (1.24, 1.76) and 1.24 (1.17, 1.31) for Cmax and AUCinf, respectively, but AUC fold increase was <2, the level used for classification of sensitive P-gp substrates. All interventions were well tolerated. In conclusion, this study supports dosing of balcinrenone/dapagliflozin without regard to food. Balcinrenone is not considered a sensitive P-gp substrate. No P-gp based dosing precautions are warranted based on this study.
Aminoglycosides require therapeutic drug monitoring due to substantial pharmacokinetic variability across individuals. While population pharmacokinetic (popPK) models have been developed for individual drugs across age groups, and cross-drug maturation models have been explored, it is unclear whether pooling data across aminoglycosides improves predictive performance. We developed and evaluated a unified multi-aminoglycoside popPK model spanning neonates, children, and adults. De-identified data from 5659 amikacin, gentamicin, and tobramycin patients at 154 US institutions were split into training and testing datasets. Predictive performance in the test dataset was evaluated using mean percent error, normalized root mean square error (nRMSE), and clinical accuracy (trough concentrations correctly classified as below or above 1 mg/L and non-troughs within 20% of observation), and compared with selected published popPK models. To assess generalizability, the final model was refit using single-drug datasets and leave-one-subgroup-out datasets. The unified model achieved the lowest nRMSE across age groups, with absolute reductions of 0.6%-24.8%. Clinical accuracy was highest for the unified model, with a posteriori accuracy in pediatric patients of 56.4% versus 48% in the best published model. Leave-one-out refits yielded similar estimates but reduced precision, while single-drug models demonstrated substantially reduced precision, and one such model was not identifiable. This unified model improved predictive performance across drugs and age groups and demonstrated robustness to exclusion of individual drug-age group combinations. These findings support use of a unified aminoglycoside model for Bayesian model-informed precision dosing and demonstrate the advantages of pooling drugs within a class and across developmental stages.
There are currently no oral treatment options for infections caused by extended spectrum β‑lactamase-producing Enterobacterales. Avibactam tomilopil, a novel oral prodrug of avibactam, is being developed in combination with the oral cephalosporin, ceftibuten, as a potential treatment for patients with complicated urinary tract infections (cUTIs). The safety, tolerability, and pharmacokinetic profiles of single and multiple doses of avibactam tomilopil (900 to 1350 mg) and ceftibuten (400 to 1600 mg), alone and/or in combination were evaluated in three Phase 1 trials in healthy participants. Avibactam tomilopil was rapidly metabolized to active avibactam and plasma avibactam exposure increased proportionately with dose. Both avibactam and cis-ceftibuten had similar plasma half-lives, and were predominantly renally excreted. While there was negligible food effect on ceftibuten exposures, plasma avibactam exposure in the fed state for a fixed-dose combination ceftibuten-avibactam tomilopil tablet was higher compared with the fasted state. Based on joint probability of target attainment simulations using a simultaneous oral ceftibuten‑avibactam tomilopil population pharmacokinetic model, a tablet formulation ceftibuten 400 mg + avibactam tomilopil 1200 mg dosed every 8 h without regard to food is proposed for Phase 3 evaluation in adult patients with cUTIs. Trial registration: NCT03931876; NCT05554237; NCT06593054.
Oliceridine is an intravenous opioid analgesic for postoperative pain control, but data on transfer into human milk and infant exposure during early breastfeeding remain limited. This study used a postpartum physiologically based pharmacokinetic (PBPK) framework to estimate oliceridine milk exposure and relative infant dose (RID) on postoperative Day 1 (0-24 h) after cesarean delivery under a reconstructed patient-controlled intravenous analgesia regimen. Maternal plasma exposure was simulated in PK-Sim; milk exposure was extrapolated using an externally specified milk-to-plasma ratio (M/P). RID was calculated from mean milk concentration, infant milk intake, and the maternal weight-normalized daily dose. An exposure scaling factor from an independent adult intravenous reference scenario was applied only as a post hoc proportional correction to RID. Morphine benchmarking assessed the physiological plausibility of the M/P extrapolation step, and a 4-24 h temporal sensitivity check examined the influence of the initial accumulation phase. In the base case, maternal plasma AUC over 0-24 h was 120.59 ng·h/mL; mean plasma and milk concentrations were both 5.025 ng/mL. The uncorrected model-predicted RID was 0.375%, and the ESF-corrected RID was 0.307%, both below the empirical 10% reference threshold. In one-way sensitivity analysis, M/P and infant milk intake had greater effects on corrected RID than maternal body weight within the prespecified ranges. The maximum corrected RID was 0.818% in the two-way scan and 1.235% under the prespecified high-exposure scenario. These findings provide a preliminary, assumption-bounded quantitative reference for modeled relative infant exposure under prespecified postoperative Day 1 extrapolation assumptions.
Busulfan, used in hematopoietic stem cell transplantation, exhibits a narrow therapeutic index and high pharmacokinetic (PK) variability. Therapeutic drug monitoring (TDM) is currently employed to achieve target exposure. However, there is no consensus on an optimal limited sampling strategy (LSS) for busulfan on the once-daily (QD) regimen. A virtual cohort of adult patients (n = 1000) receiving OD intravenous busulfan 3.2 mg/kg as a 3-h infusion was generated by Monte Carlo simulation using three published busulfan population PK models. For each one- and two-sample LSS, individual PK parameters were estimated from Day-1 sample(s) by maximum a posteriori Bayesian estimation and used to estimate the 4-day cumulative AUC. A model-informed precision-dosing (MIPD) analysis quantified the target-attainment benefit of TDM per design. The best-performing designs were validated in an external cohort (n = 37) with adults and adolescents. Across all three models, a two-sample early-plus-late schedule was the most informative, and the recommended two-sample design was 3 and 7 h after the start of infusion. TDM guided by a well-chosen LSS approximately doubled cumulative-target attainment, whereas a single early 3-h sample was markedly weaker. In the external cohort, two-sample designs recovered the cumulative 4-day AUC to ∼5%-8% MAPE versus ∼11%-13% for a single 3-h sample. For OD intravenous busulfan in adults and adolescents, a two-sample schedule at 3 and 7 h after the start of infusion supports the correct dosing decision and, through MIPD-guided dose adjustment, approximately doubles target attainment; a single 6-h sample is a simpler but less robust alternative.
Clinical pharmacology serves as the central discipline supporting rational clinical medication, innovative drug research, and full-lifecycle pharmaceutical supervision. Domestic clinical pharmacology research began in the 1950s, and the field entered a period of rapid development after 1979 across three phases. This study sorts domestic disciplinary milestones and analyzes three key datasets: among the 1949 registered drug clinical trial institutions nationwide, nearly 50% are located in East China; investigational new drug applications surged from 446 (2012) to 3516 (2025); and the Center for Drug Evaluation issued 631 technical guidelines. The National Natural Science Foundation set up an independent clinical pharmacology discipline classification in 2015. The multi-tiered educational system is further elaborated: the transitional 5-year pharmacy (clinical pharmacology direction) track, standardized 5-year clinical pharmacy undergraduate programs, and clinical pharmacology-oriented postgraduate research sub-disciplines under pharmacy-related majors. Although the field has built a complete framework covering basic research, clinical practice and regulatory evaluation, critical bottlenecks persist. Clinical pharmacology is not listed as an independent major in national undergraduate and postgraduate catalogues, resulting in uneven educational standards, insufficient industry-academia integration, and striking regional gaps in disciplinary resources between eastern and inland areas. China's transitional undergraduate training model and phased regulatory improvements provide practical references for pharmaceutical regulators and educators worldwide. Targeted optimization strategies are proposed to construct unified tiered educational systems, deepen cross-stakeholder collaborative innovation, and balance regional disciplinary layouts. The sound and balanced development of clinical pharmacology will continuously advance standardized clinical medication, accelerate domestic new drug innovations, and strengthen national public health protection.
Despite the recent reports of the potential association between semaglutide and nonarteritic anterior ischemic optic neuropathy (NAION), available evidence remains inconclusive. We aimed to evaluate the relative effect (RE) of NAION in individuals treated with semaglutide compared to the control group. The results of this systematic review and meta-analysis were reported according to the PRISMA guidelines. The study protocol was prospectively registered in PROSPERO with ID: CRD42025649542. A systematic search was performed on the PubMed, Embase, and Cochrane Library databases until May 18, 2026. Meta-analysis of REs with 95% confidence intervals (CI) was calculated using random-effects models. Eight observational cohort studies, involving a total of 5,916,559 participants, were included in the meta-analysis. Of these, 1,870,346 patients received semaglutide treatment, while 4,046,213 were administered non-semaglutide treatment. Compared to non-semaglutide-treated patients, semaglutide users had a higher risk of NAION (RE, 1.93; 95% CI, 1.22-3.08; I2, 91%; P = .01). There was a significant association between NAION risk and semaglutide use in individuals with diabetes (RE, 1.84; 95% CI, 1.21-2.80; I2, 88.26%; P < .01). However, the results were non-significant among overweight or obese individuals (RE, 1.68; 95% CI, 0.72-3.91; I2, 83.98%; P = .23). The current meta-analysis suggests a possible association between semaglutide and risk of NAION. Further randomized clinical trials are required to draw a clear conclusion.
Ischemic stroke remains a leading cause of death and disability worldwide, and bleeding (particularly intracranial hemorrhage) continues to limit conventional antithrombotic therapy in secondary prevention, even with direct oral anticoagulants. Factor XI (FXI) has emerged as a promising target: it amplifies thrombin generation and stabilizes pathological thrombi while contributing only marginally to physiological hemostasis, as illustrated by the mild bleeding phenotype of congenital FXI deficiency. This biological dissociation underpins the concept of hemostasis-sparing anticoagulation. Three pharmacological classes are being studied, with distinct pharmacokinetic, pharmacodynamic, and drug-drug interaction profiles: small-molecule oral FXIa inhibitors (asundexian and milvexian), FXI antisense oligonucleotides (fesomersen), and monoclonal antibodies targeting FXI/FXIa (abelacimab and osocimab). Oral small molecules offer rapid, reversible target engagement particularly suited to chronic cerebrovascular prevention. While phase II trials (PACIFIC-Stroke, AXIOMATIC-SSP) showed neutral primary endpoints with reassuring safety, the phase III OCEANIC-STROKE trial demonstrated that asundexian 50 mg once daily, added to antiplatelet therapy, reduced recurrent ischemic stroke by 26% (HR 0.74; 95% CI 0.65-0.84) without significant bleeding excess in non-cardioembolic stroke; the ongoing LIBREXIA-STROKE is testing milvexian 25 mg twice daily in a similar setting. Conversely, OCEANIC-AF showed that FXIa inhibition alone is insufficient versus apixaban in atrial fibrillation, indicating dependence upon clinical setting and suggesting the need for a precision-medicine approach integrating clinical, imaging, and biomarker-based patient stratification. This narrative review integrates pathophysiological rationale, comparative pharmacology of all FXI-targeting classes, trial evidence, and patient stratification, providing an up-to-date reference for FXI/FXIa inhibition in secondary ischemic stroke prevention.
This first-in-human study evaluated the safety, pharmacokinetics (PK), food effect, and pharmacodynamics (PD) of AJM347, a novel orally active, selective α4β7 integrin antagonist, in healthy Caucasian and Japanese adult males. The study consisted of three parts. In the single-ascending dose (SAD) study (Part 1), AJM347 was administered in doses ranging from 6 to 2420 mg. The effect of food was evaluated in Part 2. In the multiple-ascending dose (MAD) study (Part 3), AJM347 was administered twice daily (200-800 mg) for 7 days. Single and multiple oral doses of AJM347 were safe and well tolerated. No changes in lymphocyte counts in whole blood and cerebrospinal fluid were observed. AJM347 was rapidly absorbed and the active metabolite, CAN2281, was rapidly formed. Administration of AJM347 after meals achieved higher trough concentrations of CAN2281 compared with administration under fasted conditions. AJM347 rapidly and dose-dependently inhibited mucosal addressin cell adhesion molecule-1 binding to CD4+ T cells. Doses ≥200 mg twice daily maintained >90% inhibition (α4β7 receptor occupancy) for up to 24 h. PD effects correlated well with plasma concentrations of the active metabolite CAN2281. AJM347 demonstrated a favorable safety profile, effective target engagement, and promising PK properties for oral administration. The timing of dosing relative to meals did not affect the safety or overall PK profiles, but postprandial administration led to higher trough concentrations, suggesting that dosing after meals may represent the optimal regimen for the continued clinical development of AJM347. Blood samples were collected to assess PK and PD (α4β7 receptor occupancy). Samples were also collected to measure lymphocyte counts in peripheral blood and cerebrospinal fluid (CSF).
Esomeprazole, a proton pump inhibitor (PPI), is widely approved for gastroesophageal reflux disease (GERD) in adults and pediatrics globally, but prior to December 2022, its oral tablets (20 and 40 mg) were approved only for adults in China. To address unmet needs in Chinese adolescents aged 12-17 years, physiologically based pharmacokinetic (PBPK) modeling was employed to extrapolate data and support label extension, leveraging similarities in GERD pathophysiology and PK/PD relationships across ages and ethnicities. A PBPK model was developed for esomeprazole to capture the enteric-coated formulation's pharmacokinetics. The model was validated against clinical PK studies in Caucasian, Japanese, and Chinese adults and/or adolescents, demonstrating good predictions of concentration-time profiles and area under the curve (AUC) for CYP2C19-specific genotypes as well as overall populations across these ethnic groups. All predicted-to-observed ratios for AUC fell within 0.5- to 2.0-fold, with 14 out of 18 predictions within the 0.67- to 1.5-fold. This robust validation enabled the model's application to predict PK in Chinese adolescents. PBPK predictions for Chinese adolescents indicated that steady-state AUC for 20- and 40-mg doses was comparable to that in Japanese adolescents and slightly higher than in Caucasian adolescents. By integrating an established PK/PD relationship between AUC and the percentage of time with intragastric pH >4, once-daily doses of 20 or 40 mg were justified, achieving adequate acid suppression with a favorable safety profile. This PBPK-informed extrapolation was accepted by China's National Medical Products Administration (NMPA), enabling GERD indication extension to adolescents.
Preclinical studies suggest that tamoxifen (TAM) may interact with the efflux transporter P-glycoprotein (P-gp); however, its effect on intestinal P-gp activity in vivo remains poorly characterized. This study evaluated intestinal P-gp activity in women receiving tamoxifen therapy using fexofenadine (FEXO) as a probe substrate. Sixteen women receiving tamoxifen (20 mg/day for ≥80 days) and 12 healthy women were enrolled. All participants received a single oral dose of fexofenadine (120 mg), and serial plasma samples were collected over 12 h. Pharmacokinetic parameters were determined by noncompartmental analysis, and plasma fexofenadine concentrations were quantified by LC-MS/MS. Systemic exposure to fexofenadine was lower in women receiving tamoxifen than in healthy women. Geometric mean (95% confidence interval [CI]) AUC0-12h was 646.55 ng.h/mL (523.50-798.52) in the tamoxifen group and 994.77 ng.h/mL (832.21-1189.07) in healthy women, whereas AUC0-∞ was 715.40 ng.h/mL (588.92-869.05) and 1123.66 ng.h/mL (919.98-1372.43), respectively (P < .05). Apparent oral clearance (CL/F) was higher in women receiving tamoxifen (167.74 vs 106.79 L/h; P < .05), whereas elimination half-life was unchanged between groups. The observed pharmacokinetic profile is consistent with reduced oral bioavailability and suggests modulation of intestinal transporter-mediated drug disposition during tamoxifen therapy. These findings may have implications for the disposition of concomitantly administered orally administered P-gp substrates and warrant further investigation in dedicated clinical pharmacology studies.
Vancomycin therapeutic drug monitoring has moved toward area under the concentration-time curve (AUC)-guided dosing, but the clinical meaning of a Bayesian-estimated AUC generated at an individual monitoring episode remains uncertain when renal clearance may already be changing. We conducted a retrospective multicenter cohort study using inpatient dosing, pharmacy, therapeutic drug monitoring, and laboratory data from two hospitals in Hai Phong, Viet Nam, between 2019 and 2025. The analysis included 898 adult index vancomycin monitoring episodes with valid Bayesian-estimated AUC24 and sufficient serum creatinine data to ascertain acute kidney injury (AKI) within 48 h. AUC24 was estimated within the institutional Bayesian monitoring workflow using SmartDoseAI, with BestDose version 2.4.3 used as an independent pharmacokinetic cross-check in selected clinically uncertain episodes. AKI occurred in 84 episodes (9.4%). Higher continuous AUC24 was associated with AKI in the minimally adjusted model (odds ratio, 1.16 per 100 mg·h/L; 95% confidence interval, 1.02-1.33; P = .023), whereas categorical AUC contrasts were imprecise. The association attenuated after exclusion of 23 episodes with possible pre-existing AKI before the index monitoring episode (odds ratio, 1.12; 95% confidence interval, 0.96-1.31; P = .159), and restricted cubic spline modeling did not identify a distinct nonlinear threshold. Bayesian-estimated AUC24 at monitoring may therefore be most useful as a near-term renal risk signal that integrates vancomycin exposure with evolving renal clearance, rather than as a standalone causal toxicity threshold.
Camlipixant is a highly selective P2X3 receptor antagonist with demonstrated efficacy in pre-clinical models of evoked cough. We report the safety, tolerability, and pharmacokinetics of camlipixant in healthy participants. This Phase 1, double-blind, randomized study evaluated single ascending doses (SAD; 50/100/200/400/800/1200 mg) and multiple ascending doses (MAD; 100/200/400 mg, twice daily [BID]) of oral camlipixant versus placebo. Ninety participants were included (SAD n = 60; MAD n = 30). Treatment-emergent adverse event (TEAE) incidence was similar between camlipixant (32/72) and placebo (9/18). TEAEs were mostly mild (83%), and the most common with camlipixant was dysgeusia, primarily at doses ≥400 mg (n = 13), versus 50-200 mg (n = 1). Camlipixant was rapidly absorbed (time to maximum plasma concentration SAD: 0.77-2.29 h; MAD: 0.50-2.00 h), with a short half-life (SAD 4.28-6.71 h; MAD 7.60-8.39 h). In both cohorts, maximum plasma concentration (Cmax) increased proportionally with dose. The area under the curve extrapolated to infinity (AUC0-∞) increased proportionally with dose in the SAD cohort; the increase was slightly supra-proportional in the MAD cohort (steady state reached on Day 2). The geometric mean apparent volume of distribution ranged from 44.9 to 70.2 L and clearance from 5.7 to 10.4 L/h in the SAD cohort. Pharmacokinetics were unaffected by food (geometric mean fed/fasted ratio Cmax 91.4% [90% confidence interval, CI, 69.8-119.6]; AUC0-∞ 105.5% [90% CI, 89.8-124.0]). In summary, camlipixant was well tolerated, with pharmacokinetics supporting BID dosing and further clinical development for refractory chronic cough.
The development and approval of biosimilars are imperative for improving patient access to safe and effective treatments. This article summarizes the regulatory approval for Tyruko, the first FDA-approved biosimilar for natalizumab for the treatment of multiple sclerosis and Crohn's disease. Biosimilarity between the proposed biosimilar and the reference product was demonstrated through a comprehensive comparative assessment that included structural and functional characterization, pharmacokinetics (PK)/pharmacodynamics (PD) data, immunogenicity, and safety. The PD assessment incorporated a panel of biomarkers indicative of target engagement and downstream biological responses. The current case underscores the importance of the 351(k) pathway and highlights how the PD-based approach, in conjunction with comparative analytical assessments and PK data, supported the approval of the biosimilar through a study design relying on fewer subjects and a shorter duration compared to an efficacy study.
