Optimal Dosing Regimen Research Articles

Population pharmacokinetics of daptomycin in critically ill patients receiving extracorporeal membrane oxygenation.

Daptomycin is widely used in critically ill patients for Gram-positive bacterial infections. Extracorporeal membrane oxygenation (ECMO) is increasingly used in this population and can potentially alter the pharmacokinetic (PK) behaviour of antibiotics. However, the effect of ECMO has not been evaluated in daptomycin. Our study aims to explore the effect of ECMO on daptomycin in critically ill patients through population pharmacokinetic (PopPK) analysis and to determine optimal dosage regimens based on both efficacy and safety considerations. A prospective, open-label PK study was carried out in critically ill patients with or without ECMO. The total concentration of daptomycin was determined by UPLC-MS/MS. NONMEM was used for PopPK analysis and Monte Carlo simulations. Two hundred and ninety-three plasma samples were collected from 36 critically ill patients, 24 of whom received ECMO support. A two-compartment model with first-order elimination can best describe the PK of daptomycin. Creatinine clearance (CLCR) significantly affects the clearance of daptomycin while ECMO has no significant effect on the PK parameters. Monte Carlo simulations showed that, when the MICs for bacteria are ≥1 mg/L, the currently recommended dosage regimen is insufficient for critically ill patients with CLCR > 30 mL/min. Our simulations suggest 10 mg/kg for patients with CLCR between 30 and 90 mL/min, and 12 mg/kg for patients with CLCR higher than 90 mL/min. This is the first PopPK model of daptomycin in ECMO patients. Optimal dosage regimens considering efficacy, safety, and pathogens were provided for critical patients based on pharmacokinetic-pharmacodynamic analysis.

Screening and Validation of Natural Products for Drug Discovery: Key Points and Approaches

This article highlights the key points and approaches involved in the screening and validation of natural products for drug discovery. Screening assays play a vital role in evaluating the biological activities of natural product extracts or fractions, targeting specific diseases, pathways, or cellular processes of interest. In vitro studies provide further insights into the efficacy, safety, and mechanism of action of promising candidates, using isolated cells or cellular components. Cell-based assays offer a more realistic cellular environment to assess natural product effects on cell viability, proliferation, and specific functions. Animal models bridge the gap between in vitro and clinical evaluations, providing a comprehensive understanding of therapeutic effects, pharmacokinetics, and toxicity profiles. Pharmacokinetic studies examine the absorption, distribution, metabolism, and excretion of natural products, optimizing dosage regimens and predicting human efficacy. Safety evaluation encompasses toxicity studies to determine safe dosage ranges and identify potential risks. Promising candidates progress to clinical trials, where efficacy, safety, dosage, and interactions are assessed in human subjects. This comprehensive screening and validation process contributes to the development of effective and safe natural product-based drugs.

Therapeutic Potential of Ginsenosides on Bone Metabolism: A Review of Osteoporosis, Periodontal Disease and Osteoarthritis.

Ginsenosides, bioactive compounds from the genus Panax, have potential therapeutic effects on diverse ailments, including diabetes. Emerging evidence suggests their involvement in bone metabolism. The present review summarizes the current understanding of the effects of ginsenosides on osteoporosis, periodontal disease, and osteoarthritis. Their mechanisms of action include effects on osteoblasts, osteoclasts, periodontal ligament fibroblasts (PDLFs), and chondrocytes, which are pivotal in maintaining bone, periodontal tissue, and cartilage homeostasis. Ginsenosides may exert their beneficial effects by enhancing PDLF and osteoblast activity, suppressing osteoclast function, augmenting chondrocyte synthesis in the cartilage matrix, and mitigating connective tissue degradation. Moreover, they possess antioxidant, anti-inflammatory, antimicrobial, and anti-pyroptotic properties. Their efficacy in increasing bone density, ameliorating periodontitis, and alleviating osteoarthritis symptoms has been demonstrated in preclinical studies using animal models. In terms of their mechanism of action, ginsenosides modulate cellular differentiation, activity, and key signaling pathway molecules, such as mitogen-activated protein kinases (MAPKs), while also regulating various mediators. Furthermore, the symptomatic relief observed in animal models lends further credence to their therapeutic utility. However, to translate these preclinical findings into clinical practice, rigorous animal and clinical investigations are imperative to ascertain the safety, efficacy, and optimal dosing regimens in human subjects.

Dispelling the Myths of Isotretinoin and Implications for Rhinoplasty

Summary: Despite concerns from 1980s case reports, oral isotretinoin, a derivative of Vitamin A, has largely proven to be safe in surgical procedures with the exception of deep skin resurfacing. Isotretinoin modulates thinning skin and internal scarring in select rhinoplasty patients who may otherwise have poor definition and excessive scarring. A review of patients undergoing surgical interventions including rhinoplasty in the setting of concomitant isotretinoin was performed to examine safety and therapeutic potential. Forty-nine studies were reviewed. Isotretinoin use appears to be safe in a wide variety of surgical procedures relying on internal scar formation. In rhinoplasty, studies utilized oral isotretinoin to thin skin and improve appearance, patient and surgeon satisfaction. As such, the clinical potential for using oral isotretinoin in select rhinoplasty candidates such as those with thick glaborous sebaceous skin, ethnic, male, and/or revision patients, could mitigate internal scarring processes. Further studies examining the optimal dosing regimen and long-term benefits are warranted.

Exogenous Ketone Esters as a Potential Therapeutic for Treatment of Sarcopenic Obesity.

Identifying effective treatment(s) for sarcopenia and sarcopenic obesity are of paramount importance as the global population advances in age and obesity continues to be a worldwide concern. Evidence has shown that a ketogenic diet can be beneficial for preservation of muscle quality and function in older adults, but long-term adherence is low due in part to the high-fat (> 80%), very low carbohydrate (< 5%) composition of the diet. When provided in adequate amounts, exogenous ketone esters can increase circulating ketones to concentrations that exceed those observed during prolonged fasting or starvation without significant alterations in the diet. Ketone esters first emerged in the mid-1990s and their use in pre-clinical and clinical research has escalated within the past 10-15 years. We present findings from a narrative review of the existing literature for a proposed hypothesis on the effects of exogenous ketones as a therapeutic for preservation of skeletal muscle and function within the context of sarcopenic obesity and future directions for exploration. Much of the reviewed literature herein examines the mechanisms of the ketone diester (R, S-1,3-butanediol diacetoacetate) on skeletal muscle mass, muscle protein synthesis, and epigenetic regulation in murine models. Additional studies are needed to further examine the key regulatory factors producing these effects in skeletal muscle, examine convergent and divergent effects among different ketone ester formulations, and establish optimal frequency and dosing regimens to translate these findings into humans.

Development of Physiologically Based Biopharmaceutical Model (PBBM) for Felodipine Prolonged-Release Tablet as useful tool for prediction of formulation.

Physiologically Based Biopharmaceutical Models (PBBMs) are advanced tools that integrate physiological parameters with drug-specific properties to simulate drug behavior in vivo. In this study, we present the development of a PBBM specifically tailored for felodipine prolonged-release (PR) tablet formulations. Felodipine, a potent calcium channel blocker, is widely used for the treatment of hypertension and angina pectoris. Prolonged-release formulations aim to provide controlled drug release, ensuring sustained therapeutic effect with reduced dosing frequency and minimized adverse effects. Our PBBM incorporates key physiological processes such as gastrointestinal transit, drug dissolution, absorption, distribution, metabolism, and elimination. Data from in vitro dissolution studies, preclinical pharmacokinetics, and clinical observations are integrated to parameterize the model accurately. Special attention is given to the physicochemical properties of felodipine and the release characteristics of the PR tablet formulation. Validation of the PBBM is conducted against clinical pharmacokinetic data obtained from bioequivalence studies and population pharmacokinetic analyses of felodipine PR tablets. The model may demonstrate excellent predictive performance, accurately capturing plasma concentration-time profiles across different dosing regimens and patient populations. The developed PBBM provides valuable insights into the biopharmaceutical behavior of felodipine PR tablets, facilitating rational formulation design, dosage regimen optimization, and therapeutic individualization. It serves as a powerful tool for drug developers, regulatory agencies, and clinicians to enhance the efficiency and effectiveness of drug development and clinical pharmacotherapy

Fundamentals of rational antibiotic therapy in outpatient pediatrics

Antibiotics are one of the most prescribed groups of drugs in outpatient pediatric practice. To date, there are still disagreements about the need for the use of antibiotics and the optimal dosage regimen for many infections that pediatricians face daily. The authors conducted a search for publications in the PubMed, Google Scholar and eLibrary by the following keywords: «pediatric,» «antibiotics,» «antibiotic resistance,» «outpatient pediatrics» in English, and «педиатрия,» «антибиотики,» «антибиотикорезистентность,» «амбулаторная педиатрия» in Russian. Recent studies show that uncomplicated childhood infectious diseases in vaccinated children can be treated with shorter courses of antibiotics. The rational use of antibiotics in outpatient pediatric practice is of great importance for reducing resistance to them. Since the first step in choosing treatment tactics is to establish the etiology of the disease, future research should focus more on identifying potential biomarkers and diagnostic tests that allow rapid diagnosis of the etiology of an infectious disease, as well as optimizing the dosage and duration of antibiotic therapy courses.

Antifungals in Patients With Extracorporeal Membrane Oxygenation: Clinical Implications.

Extracorporeal membrane oxygenation (ECMO) is a life-saving technique used in critical care medicine for patients with severe respiratory or cardiac failure. This review examines the treatment and prophylaxis of fungal infections in ECMO patients, proposing specific regimens based on available data for different antifungals (azoles, echinocandins, amphotericin B/liposomal amphotericin B) and invasive fungal infections. Currently, isavuconazole and posaconazole have the most supported data, while modified dosages of isavuconazole are recommended in ECMO. Echinocandins are preferred for invasive candidiasis. However, choosing echinocandins is challenging due to limited and varied data on concentration loss in the ECMO circuit. Caution is likewise advised when using liposomal amphotericin B due to uncertain concentrations and potential ECMO dysfunction based on scarce data. We further conclude with the importance of further research on the impact of ECMO on antifungal drug concentrations to optimize dosing regimens in critically ill patients.

Integrated models of population pharmacokinetics and exposure response to optimize dosage regimen for anaprazole sodium in duodenal ulcer

Anaprazole sodium enteric-coated tablet is a novel proton pump inhibitor which has been approved for the treatment of duodenal ulcer. The aim of this study is to provide reliable information for the design of an optimal dosage regimen. Population pharmacokinetics and exposure-response models were integrated to evaluate the pharmacokinetic parameters and covariates of Anaprazole and its metabolite M21-1, and subsequently provided dosage suggestions based on clinical trials and simulation data. A pharmacokinetic model incorporating two-compartment for the parent drug and one-compartment for the metabolite, with both first-order and zero-order mixed absorption was used to describe the pharmacokinetics of Anaprazole and M21-1. Age emerged as a significant covariate affecting the elimination rate constant of M21-1, with clearance decreasing as age advances. No correlation was observed between the pharmacokinetics of Anaprazole or M21-1 and the adverse reactions under the current dosages. BMI might be the influence factor of the mild gastrointestinal adverse reactions. Meanwhile, Anaprazole had a good healing rate (94.0 %) in duodenal ulcer patients and the exposure-response analysis indicated that the cured results were not influenced by the exposure parameters of parent drug or metabolite. In conclusion, the drug is safe when dosing between 20 and 100 mg once a day.

Enhancing Therapeutic Efficacy and Safety of Immune Checkpoint Inhibition for Bladder Cancer: A Comparative Analysis of Injectable vs. Intravesical Administration.

Bladder cancer (BC) presents a significant global health burden, characterized by high recurrence rates post-initial treatment. Gender differences in BC prevalence and response to therapy emphasize the importance of personalized treatment strategies. While Bacillus Calmette-Guérin (BCG) remains a cornerstone of BC therapy, resistance poses a challenge, necessitating alternative strategies. Immune checkpoint inhibitors (ICIs) have shown promise, yet systemic toxicity raises concern. Intravesical administration of ICIs offers a potential solution, with recent studies demonstrating the feasibility and efficacy of intravesical pembrolizumab. Although systemic toxicity remains a concern, its localized administration may mitigate adverse events. Additionally, liposomal delivery of ICIs exhibits promises in enhancing drug penetration and reducing toxicity. Novel imaging modalities compatible with Vesical Imaging-Reporting and Data System (VI-RADS) and capable of predicting high-grade bladder cancer can aid the pre-operative shared decision making of patient and surgeon. Future research should focus on refining treatment approaches, optimizing dosing regimens, and leveraging advanced imaging techniques to improve patient outcomes. In conclusion, intravesical immunotherapy presents a promising avenue for BC treatment, offering enhanced therapeutic effectiveness while minimizing systemic toxicity. Continued research efforts are essential to validate these findings and optimize intravesical immunotherapy's role in BC management, ultimately improving patient outcomes.

Comprehensive medication management (CMM): Application of a new pharmaceutical practice in onco-hematology

The integration of a large number of drugs, such as antineoplastic agents and cancer-related supportive care drugs, into the management of cancer patients exposes them to an increased number of drug-related problems (DRP). Clinical pharmacists contribute to drug management by actively intervening in detected DRP. The aim of this study is to assess the impact of the applying a clinical pharmacist-driven comprehensive medication management (CMM) service to onco-hematology patients. This prospective interventional study was carried out over six-month duration, specifically from November 06, 2022 to April 5, 2023 in the oncology and hematology departments of the EHU Oran. The adherence to treatment was evaluated using the 8-item Morisky Medication Adherence Scale (MMAS). Whereas data related to the patient's general condition and medication history was assessed using the Pharmaceutical Care Network Europe (PCNE) Classification for Drug-Related Problems V9.1. Among the 130 patients included in the study, a total of 879 DRP were identified, with a mean of 6.78 (±1.72) DRP/patient, half of which were related to efficacy (51%). Almost half of our sample (44.6%) did not adhere to their treatment. The most frequent cause of DRP, accounting for (19.9%) of the cases, was the inappropriate administration by a health professional. A total of 875 pharmaceuticals interventions (PI) were proposed, 67.2% of which were focused at the drug level. The PI acceptance rate was 94.1%. The integration of CMM services in onco-hematology played an important role in optimizing dosing regimen and treatment administration methods, as well as preventing iatropathology in the management of cancer patients.

Unlocking Vitality: A Comprehensive Review of Vitamin D's Impact on Clinical Outcomes in Critically Ill Children.

This comprehensive review explores the multifaceted role of vitamin D (VD) in critically ill children, examining its implications for clinical outcomes. Although this substance has long been known for its function in maintaining bone health, it is now becoming more widely known for its extensive physiological effects, which include immune system and inflammation regulation. Observational research consistently associates VD levels with outcomes like duration of hospitalization, mortality, and illness severity in critically ill pediatric patients. Mechanistically, it exerts anti-inflammatory and endothelial protective effects while modulating the renin-angiotensin system. Increasing VD levels through supplementation presents promise as a therapeutic strategy; however, further research is necessary to elucidate optimal dosage regimens and safety profiles. This review emphasizes the significance of comprehending the intricate relationship between VD and critical illnesses among pediatric populations.

Managing Severe Cancer Pain with Oxycodone/Naloxone Treatment: A Literature Review Update.

Severe cancer pain substantially affects patients' quality of life, increasing the burden of the disease and reducing the disability-adjusted life years. Although opioid analgesics are effective, they may induce opioid-induced bowel dysfunction (OIBD). Oxycodone/naloxone combination therapy has emerged as a promising approach to mitigate opioid-induced constipation (OIC) while providing effective pain relief. This review provides an updated analysis of the literature of the last decade regarding the use of oxycodone/naloxone in the management of severe cancer pain. Through a comprehensive search of databases, studies focusing on the efficacy, safety, and patient experience of oxycodone/naloxone's prolonged release in severe cancer pain management were identified. Furthermore, the literature discusses the mechanism of action of naloxone in mitigating OIC without compromising opioid analgesia. Overall, the evidence suggests that oxycodone/naloxone combination therapy offers a valuable option for effectively managing severe cancer pain while minimizing opioid-induced constipation, thereby improving patients' quality of life. However, further research is needed to optimize dosing regimens, evaluate long-term safety, and assess patient outcomes in diverse cancer populations.

Cross-protective efficacy and safety of an adenovirus-based universal influenza vaccine expressing nucleoprotein, hemagglutinin, and the ectodomain of matrix protein 2

It is necessary to develop universal vaccines that act broadly and continuously to combat regular seasonal epidemics of influenza and rare pandemics. The aim of this study was to find the optimal dose regimen for the efficacy and safety of a mixture of previously developed recombinant adenovirus-based vaccines that expressed influenza nucleoprotein, hemagglutinin, and ectodomain of matrix protein 2 (rAd/NP and rAd/HA-M2e). The vaccine efficacy and safety were measured in the immunized mice with the mixture of rAd/NP and rAd/HA-M2e intranasally or intramuscularly. The minimum dose that would be efficacious in a single intranasal administration of the vaccine mixture and cross-protective efficacy against various influenza strains were examined. In addition, the immune responses that may affect the cross-protective efficacy were measured. We found that intranasal administration is an optimal route for 107 pfu of vaccine mixture, which is effective against pre-existing immunity against adenovirus. In a study to find the minimum dose with vaccine efficacy, the 106 pfu of vaccine mixture showed higher antibody titers to the nucleoprotein than did the same dose of rAd/NP alone in the serum of immunized mice. The 106 pfu of vaccine mixture overcame the morbidity and mortality of mice against the lethal dose of pH1N1, H3N2, and H5N1 influenza infections. No noticeable side effects were observed in single and repeated toxicity studies. We found that the mucosal administration of adenovirus-based universal influenza vaccine has both efficacy and safety, and can provide cross-protection against various influenza infections even at doses lower than those previously known to be effective.

Population pharmacokinetic analysis for dose regimen optimization of vancomycin in Southern Chinese children.

Changes in physiological factors may result in large pharmacokineticvariability of vancomycin in pediatric patients, thereby leading to either supratherapeutic or subtherapeutic exposure and potentially affecting clinical outcomes. This study set out to characterize the disposition of vancomycin, quantify the exposure target and establish an optimal dosage regimen among the Southern Chinese pediatric population. Routine therapeutic drug monitoring data of 453 patients were available. We performed a retrospective population pharmacokineticanalysis of hospitalized children prescribed intravenous vancomycin using NONMEM® software. A one-compartment PPK model of vancomycin with body weight and renal functions as covariates based on a cutoff of 2 years old children was proposed in this study. Both internal and external validation showing acceptable and robust predictive performance of the model to estimate PK parameters. The value of area under the curve over 24 h to minimum inhibitory concentration ratio (AUC0-24/MIC) ≥ 260 was a significant predictor for therapeutic efficacy. Monte Carlo simulations served as a model-informed precision dosing approach and suggested that different optimal dose regimens in various scenarios should be considered rather than flat dosing. The evaluation of vancomycin exposure-efficacy relationship indicated that lower target level of AUC0-24/MIC may be needed to achieve clinical effectiveness in children, which was used to derive the recommended dosing regimen. Further prospective studies will be needed to corroborate and elucidate these results.

Population Pharmacokinetics of Lamotrigine and Its N2-Glucuronide Metabolite in Chinese Patients With Epilepsy.

Lamotrigine is a new antiepileptic drug with substantial interindividual variability in its pharmacokinetics and therapeutic responses. This study aimed to develop population pharmacokinetic (PPK) models of lamotrigine and its N2-glucuronide metabolites for model-informed individualized therapy. A total of 353 plasma concentrations from Chinese patients with epilepsy receiving oral lamotrigine were used to develop a population PPK model using a nonlinear mixed effects modeling method. One- and two-compartment models were applied to the nonmetabolite and metabolite model, respectively. Forward addition and backward elimination were used to establish the final model. Model validation was performed using standard goodness-of-fit, bootstrap, visual predictive checks, and normalized prediction distribution errors. Finally, simulations were performed to propose lamotrigine dosages in different situations to achieve trough concentrations within the reference interval (2.5-15 mg/L). For both final population PPK models, coadministration with valproic acid (VPA) or enzyme inducer, and body weight significantly affected lamotrigine clearance. The final models for lamotrigine clearance were and for nonmetabolite and metabolite models, respectively. The precision of the PPK parameters was acceptable, and the models exhibited good predictability. Monte Carlo simulations revealed that the lamotrigine dosage administered to patients combined with an enzyme inducer must be tripled that administered with VPA to reach the target trough concentration. Variability in the pharmacokinetics of lamotrigine is large. Coadministration of VPA or an enzyme inducer and body weight are the most important factors in lamotrigine clearance in Chinese patients with epilepsy. The developed population PPK models might support further optimization of lamotrigine dosing regimens.

Perioperative Methadone for Spine Surgery: A Scoping Review.

Complex spine surgery is associated with significant acute postoperative pain. Methadone possesses pharmacological properties that make it an attractive analgesic modality for major surgeries. This scoping review aimed to summarize the evidence for the perioperative use of methadone in adults undergoing complex spine surgery. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). A search was performed using MEDLINE, CINAHL, Cochrane Library, Scopus, Embase, and Joanna Briggs between January 1946 and April 2023. The initial search identified 317 citations, of which 12 met the criteria for inclusion in the review. There was significant heterogeneity in the doses, routes of administration, and timing of perioperative methadone administration in the included studies. On the basis of the available literature, methadone has been associated with reduced postoperative pain scores and reduced postoperative opioid consumption. Though safety concerns have been raised by observational studies, these have not been confirmed by prospective randomized studies. Further research is required to explore optimal methadone dosing regimens, the potential synergistic relationships between methadone and other pharmacological adjuncts, as well as the potential long-term antinociceptive benefits of perioperative methadone administration.

Abstract LB278: Application of phase 1 and pre-clinical data to assist in determining the optimal dosage regimen for cancer drugs using the principles of Project Optimus

Abstract Background: In 2022 and 2023 FDA introduced the Project Optimus initiative and the Draft Guidance “Optimizing the Dosage of Human Prescription Drugs and Biological Products for the Treatment of Oncologic Diseases.” The FDA’s desire is to move away from the maximum tolerated dose (MTD) approach in the development of all oncology drugs and to determine and justify the optimal dosage regimen (ODR), requiring one to evaluate the exposure-response relationship for both the safety and efficacy of oncology drugs. This approach has made the oncology drug developer re-examine their previous beliefs and reconsider the design of the clinical and pre-clinical studies. Processa has begun to implement the ODR evaluation in Phase 1 and pre-clinical studies and will be providing examples as well as how the findings may potentially affect the design of Phase 2/3 trials. Methods/Results: For Next Generation Irinotecan (NGC-Iri), the toxicity and tumor growth inhibition after NGC-Iri administration (as well as tissue distribution of NGC-Iri) were compared to irinotecan in xenograft transplanted mice. Tumor growth inhibition remained constant at 100% for an NGC-Iri dose at the MTD and at 50% of the MTD. However, tumor growth inhibition after irinotecan administration decreased from 100% at the MTD to approximately 64% at 50% of the MTD. The differences seen in the tumor inhibition when NGC-Iri and irinotecan were administered illustrate that the exposure-efficacy profile of NGC-Iri follows a different pattern than the exposure-safety profile and is different from the irinotecan exposure-efficacy profile even though the active molecule is the same. The dose of NGC-Iri can be decreased to improve safety while not significantly sacrificing efficacy, different than what was seen with irinotecan. In a second example, we are evaluating the PK-safety relationship of a different Next Generation drug in our ongoing Phase 1 trial. We have recently found that the exposure-safety relationship is different for our NGC drug than for the approved drug with the same cancer-killing metabolite(s). Based on the difference in exposure-response in the Phase 1 study, we are designing the Phase 2 trial to determine the potential ODR. Conclusion: Both preclinical and Phase 1 oncology trials can be designed to better understand the exposure-response relationships for safety and efficacy which will then help the drug developer in designing the Phase 2 and 3 trials for eventual FDA approval of the ODR. Citation Format: David Young, Sian Bigora, Peter Franks, Mary Nyberg, Yvonne Madden. Application of phase 1 and pre-clinical data to assist in determining the optimal dosage regimen for cancer drugs using the principles of Project Optimus [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB278.

Beyond One-Size-Fits-All: Tailoring Teicoplanin Regimens for Normal Renal Function Patients Using Population Pharmacokinetics and Monte Carlo Simulation.

In patients with normal renal function, significant teicoplanin dose adjustments are often necessary. This study aimed to develop a population pharmacokinetic (PK) model for teicoplanin in healthy adults and use it to recommend optimal dosage regimens for patients with normal renal function. PK samples were obtained from 12 subjects and analyzed using a population approach. The derived parameters informed Monte Carlo simulations for dosing recommendations. The PK profile was best described using a three-compartment model, in which the estimated glomerular filtration rate calculated via the CKD-EPI equation and adjusted for body surface area was identified as a significant covariate affecting total clearance. For pathogens with a minimum inhibitory concentration of 1 mg/L, a loading dose (LD) of 14 mg/kg administered every 12 h for four doses, followed by a maintenance dose (MD) of 16 mg/kg administered every 24 h, is recommended. These findings indicate the need for dosage adjustments, such as increasing the LD and MD or decreasing the dosing interval of MD in patients with normal renal function. Because of the long half-life of teicoplanin and the requirement for long-term administration, therapeutic drug monitoring at strategic intervals is important to avoid nephrotoxicity associated with elevated trough concentrations.

Evaluation of Anti-epileptic Activity of Leaves of Leucas Cephalotes

Epilepsy is a neurological disorder characterized by recurrent seizures, affecting millions of people worldwide. Despite advancements in therapeutic interventions, there remains a need for novel and effective treatments with fewer side effects. This study aimed to evaluate the anti-epileptic potential of Leucas cephalotes leaves through experimental models. The leaves of Leucas cephalotes were collected, dried, and subjected to extraction using suitable solvents. The obtained extract was then evaluated for acute toxicity using standard guidelines. Subsequently, anti-epileptic activity was assessed using chemically induced seizure models in rodents. Behavioral observations, seizure latency, duration, and severity were recorded to determine the extract's efficacy. Preliminary phytochemical analysis of the extract revealed the presence of alkaloids, flavonoids, terpenoids, and phenolic compounds, which are known for their neurological effects. Acute toxicity testing indicated the safety of the extract at tested doses. In seizure models, the extract demonstrated a significant increase in seizure latency, reduction in seizure duration, and alleviation of seizure severity compared to control groups. These findings suggest that the leaves of Leucas cephalotes possess anti-epileptic properties, possibly attributed to the presence of bioactive compounds. Further studies are warranted to elucidate the underlying mechanisms and optimize dosage regimens for clinical application. Leucas cephalotes could emerge as a promising natural source for developing anti-epileptic agents with improved safety profiles.