Article
Medicine, Research & Experimental
Ioannis Loisios-Konstantinidis, Jennifer Dressman
Summary: PBPK/PD modeling is widely used to predict in vivo drug performance, but there are challenges with regulatory acceptance, incomplete physiological understanding, and model validation, which can limit their translatability and predictive performance. Advances in GI physiology and mechanistic tools will play a key role in the future development of PBBM.
MOLECULAR PHARMACEUTICS
(2021)
Review
Infectious Diseases
Gauri G. Rao, Cornelia B. Landersdorfer
Summary: The use of pharmacokinetic/pharmacodynamic approaches is crucial in optimizing dosage regimens of anti-infectives to maximize efficacy, minimize toxicity and resistance, and ensure a high likelihood of therapeutic success. This involves well-designed preclinical studies, mathematical-model-based analysis, in-silico simulations, and the integration with population pharmacokinetic modelling to consider interindividual variability and predict treatment outcomes in patients. The importance of this approach is highlighted through the example of Polymyxin B, showcasing the necessity of pharmacokinetic/pharmacodynamic modelling in conjunction with experimentation for successful translation to clinical practice.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2021)
Review
Veterinary Sciences
Longfei Zhang, Hongbing Xie, Yongqiang Wang, Hongjuan Wang, Jianhe Hu, Gaiping Zhang
Summary: Pharmacokinetic/pharmacodynamic (PK/PD) integration models are used to investigate the antimicrobial activity characteristics of drugs targeting pathogenic bacteria through comprehensive analysis of the interactions between PK and PD parameters. PK/PD models have been widely applied in the development of new drugs, optimization of the dosage regimen, and prevention and treatment of drug-resistant bacteria.
FRONTIERS IN VETERINARY SCIENCE
(2022)
Article
Pharmacology & Pharmacy
Sathish Dharani, Eman M. Mohamed, Tahir Khuroo, Ziyaur Rahman, Mansoor A. Khan
Summary: This study aimed to improve the physicochemical properties and oral bioavailability of dasatinib by using the amorphous solid dispersion approach. The results showed that the ASD formulation significantly increased dissolution and oral bioavailability compared to the physical mixture.
Review
Biochemistry & Molecular Biology
Romain Pelletier, Brendan Le Dare, Diane Le Bouedec, Angeline Kernalleguen, Pierre-Jean Ferron, Isabelle Morel, Thomas Gicquel
Summary: Since the 2000s, there has been an increase in the availability of new psychoactive substances (NPS) on the drug market. Arylcyclohexylamine (ACH) compounds, such as ketamine and its derivatives, have raised concerns due to their growing use and lack of detailed toxicity information. Initially used for anesthesia, these compounds are now increasingly used recreationally. ACH derivatives exhibit antagonistic activity against the N-methyl-D-aspartate receptor, resulting in dissociative effects. Synthetic ketamine derivatives from Asia are making their way to Europe, where they are often not classified as narcotics and therefore legal. This article discusses the pharmacology, epidemiology, chemistry, metabolism, and case reports of intoxication related to ACH derivatives.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Soyoung Lee, Kyung Taek Hong, Seol Ju Moon, Jung Yoon Choi, Che Ry Hong, Hee Young Shin, Joo-Youn Cho, In-Jin Jang, Kyung-Sang Yu, Jaeseong Oh, Hyoung Jin Kang
Summary: The study evaluated the pharmacokinetics, pharmacodynamics, and safety of tripegfilgrastim in pediatric patients, showing extended detectability in plasma and slightly less than dose proportionally increase in plasma concentrations. There were no significant differences in pharmacokinetic and pharmacodynamic responses between age groups and weight stratifications in pediatric patients.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Pharmacology & Pharmacy
Carmen Flores-Perez, Luis Alfonso Moreno-Rocha, Juan Luis Chavez-Pacheco, Norma Angelica Noguez-Mendez, Janett Flores-Perez, Delfina Ortiz-Marmolejo, Lina Andrea Sarmiento-Arguello
Summary: This study proposes a pharmacokinetic-pharmacodynamic (PK-PD) population model for the use of midazolam in pediatric patients undergoing minor surgery. The results demonstrate that adequate sedation without adverse effects can be achieved at half the usual dose. Further research is needed to optimize dosing schedules and prevent potential adverse effects.
Article
Chemistry, Medicinal
Albert Tang
Summary: A variety of new recurrent neural networks (RNNs) were evaluated on modeling irregularly sampled PK/PD data and predicting PD data of unseen dosing regimens and dosing levels. The RNNs were able to model daily dose (QD) PK/PD and extrapolate to twice daily (BID) dose PD based on BID PK. However, extrapolating to unseen dose levels outside of the dose range for training proved to be challenging for all the RNNs tested. Only the GRUD demonstrated reasonable prediction results when extrapolating to unseen doses that were 3 or 10-fold outside the training doses. Overall, these new RNNs showed promise of integrating neural networks in PK/PD.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Medicine, Research & Experimental
Kai Wang, Yangbing Li, Bing Chen, Hao Chen, David E. Smith, Duxin Sun, Meihua R. Feng, Gordon L. Amidon
Summary: This study focused on exploring the variability of the MMF absorption process through population PK models in the context of the wide applicability and significant plasma concentration variability of the prodrug mycophenolate mofetil. The results showed that intra-individual variability played a more significant role in explaining the variability of MMF systemic appearance.
MOLECULAR PHARMACEUTICS
(2022)
Article
Veterinary Sciences
Jeff D. Olivarez, Pierre-Yves Mulon, Lisa S. Ebner, Haley Cremerius, Channing Cantrell, Rebecca Rahn, Windy Soto-Gonzalez, Joan Bergman, Sherry Cox, Jonathan P. Mochel, Amanda J. Kreuder, Joe S. Smith
Summary: The objective of this study was to estimate the pharmacokinetic parameters of pantoprazole in neonatal calves and investigate its effect on abomasal pH. The results showed that the pharmacokinetic parameters of pantoprazole in neonatal calves were similar to previous reports. Additionally, pantoprazole significantly increased abomasal pH. These findings suggest that pantoprazole may be a potential treatment/preventative for abomasal ulcers.
FRONTIERS IN VETERINARY SCIENCE
(2023)
Review
Pharmacology & Pharmacy
Barbara Miziak, Stanislaw J. Czuczwar, Ryszard Pluta
Summary: Patients with epilepsy may require antidepressant treatment due to the high prevalence of depression in this population. There may be pharmacodynamic and pharmacokinetic interactions between antiepileptic and antidepressant drugs. Animal data suggest that chronic administration of antidepressants can either enhance or reduce the anticonvulsant activity of certain antiepileptic drugs.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Infectious Diseases
Yingying Hu, Qiong Wei, Xingchen Bian, Xinyi Yang, Jicheng Yu, Jingjing Wang, Haijing Yang, Guoying Cao, Xiaojie Wu, Jing Zhang
Summary: This study investigated the pharmacokinetics and safety of oral and intravenous lefamulin in healthy Chinese subjects, and evaluated the efficacy of the intravenous administration regimen. The results showed that lefamulin exhibited extensive distribution, and the PK parameters were consistent between oral and intravenous administration. The regimen was found to be microbiologically effective and well-tolerated.
Article
Veterinary Sciences
Ying Xu, Jie Li, Bing He, Tingsong Feng, Lijie Liang, Xianhui Huang
Summary: We evaluated the pharmacokinetics of silymarin solid dispersion in pigs and found that the bioavailability of silybin was significantly increased compared to a silymarin premix.
FRONTIERS IN VETERINARY SCIENCE
(2022)
Review
Chemistry, Medicinal
Mauricio A. Garcia, Rodrigo Cristofoletti, Bertil Abrahamsson, Dirk W. Groot, Alan Parr, James E. Polli, Mehul Mehta, Vinod P. Shah, Tajiri Tomakazu, Jennifer B. Dressman, Peter Langguth
Summary: Carbamazepine is a BCS Class 2 drug with high permeability but a narrow therapeutic index, not recommended for a BCS-based biowaiver; USP dissolution conditions effectively differentiate between bioinequivalent products, potentially aiding in predicting bioequivalence of formulations.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Biology
Mohamed Abdelaziz Zaitri, Hanaa Zitane, Delfim F. M. Torres
Summary: This paper presents a novel Pharmacokinetic/Pharmacodynamic (PK/PD) model for the induction phase of anesthesia, incorporating the Psi-Caputo fractional derivative. Numerical analysis and simulations in MATLAB are performed to explore the effects of Psi functions and fractional orders on the model. The results suggest that Psi functions and fractional differentiation play an important role in modeling individual-specific characteristics.
COMPUTERS IN BIOLOGY AND MEDICINE
(2023)
Article
Chemistry, Multidisciplinary
Hyo-Jung Lee, Yong-Bin Kwon, Ji-Hyun Kang, Dong-Won Oh, Eun-Seok Park, Yun-Seok Rhee, Ju-Young Kim, Dae-Hwan Shin, Dong-Wook Kim, Chun-Woong Park
Summary: The feasibility of using inhalable bosentan microparticles as an alternative treatment for PAH was validated in this study, showing promising results in vitro and in vivo. The microparticles exhibited superior aerodynamic performance and dissolution rate compared to raw bosentan hydrate, with no evidence of lung toxicity. The intratracheal administration of SDBM 1:1 significantly improved pharmacokinetic parameters, pulmonary arterial remodeling, and right ventricular hypertrophy in a rat model of PAH.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Pharmacology & Pharmacy
Jong-Shik Park, Sungmin Kim, Jaeyeon Lee, Jae-Cheol Choi, YoungAh Kim, Chun-Woong Park, Soohan Lee
Summary: The study comparing the bioequivalence of oral disintegrating film (ODF) and meloxicam suspension showed that ODF had a faster absorption rate and similar efficacy. Consequently, ODF can be used as an alternative to suspension formulations for the treatment of inflammatory joint diseases and painful musculoskeletal disorders.
JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS
(2021)
Article
Pharmacology & Pharmacy
Thi-Phuong-Chi Do, Duc-Cuong Nguyen, Tien-Dat Nguyen, Quang-Dong Bui, Canh-Hung Nguyen, Thanh-Binh Nguyen, Quyen-Do, Nguyen-Thach Tung
Summary: This study successfully developed a stable and highly effective capsaicin cream by optimizing the rheological stability, release behavior, and pharmacological effects through the integration of Design of Experiment approach, rheological science, and pharmacological studies. The experiment not only focused on the rheological stability and release behaviors of the drug from the cream, but also investigated its skin irritation and anti-inflammatory and analgesic effects in experimental animals. The final optimized cream did not cause irritation in rabbits and exhibited comparable anti-inflammatory and analgesic effects to the reference product.
CURRENT DRUG DELIVERY
(2021)
Article
Pharmacology & Pharmacy
Nguyen-Thach Tung, Cao-Son Tran, Tran-Linh Nguyen, Thi-Minh-Hue Pham, Sang-Cheol Chi, Hoang-Anh Nguyen, Quang-Dong Bui, Duc-Nhat Bui, Thi-Quyen Tran
Summary: This study aimed to investigate the effect of a surfactant on the oral bioavailability of a weakly basic drug (l-THP) in an amorphous solid dispersion (ASD) system. The addition of 1.5% of surfactant (Poloxamer 188) decreased the relative bioavailability of l-THP by approximately 2.4 times, while the application of binary ASD increased the oral bioavailability of l-THP by around 334.77% compared to the raw material. This study provides insights into how different dosage forms influence the bioavailability of l-THP, allowing for the selection of the optimal approach for this weakly basic drug.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Correction
Pharmacology & Pharmacy
Ji-Hyun Kang, Kwang-Hwi Yoo, Hyo-Young Park, Seung-Min Hyun, Sang-Duk Han, Dong-Wook Kim, Chun-Woong Park
Article
Biochemistry & Molecular Biology
Nguyen-Thach Tung, Thi-Hoang-Yen Dong, Cao-Son Tran, Thi-Kim-Thuy Nguyen, Sang-Cheol Chi, Danh-Son Dao, Dang-Hoa Nguyen
Summary: This study aimed to optimize the nanocrystal formulation to enhance the solubility of a poorly soluble drug and modify its release profile by integrating a fast-release phase and a sustained-release phase in a compression-coated tablet. The results showed that the optimized nanocrystal formulation and different derivatives of HPMC improved the drug release behavior.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Nanoscience & Nanotechnology
Chang -Soo Han, Ji-Hyun Kang, Young-Jin Kim, Dong-Wook Kim, Chun-Woong Park
Summary: Dry powder inhalations are a promising pharmaceutical dosage form due to their environmental friendliness, portability, and physicochemical stability. This study demonstrates that microspheres with nanoscale dimples can improve aerosolization and lung deposition, thereby enhancing the therapeutic activity of inhaled drugs.
INTERNATIONAL JOURNAL OF NANOMEDICINE
(2022)
Article
Pharmacology & Pharmacy
Yong-Bin Kwon, Ji-Hyun Kang, Young-Jin Kim, Dong-Wook Kim, Sung-Hoon Lee, Chun-Woong Park
Summary: This study successfully prepared mucus-penetrating inhalable microparticles and confirmed their effects in an asthma-induced rat model. The microparticles with sodium glycocholate showed improved morphology and smaller particle size distribution, allowing better aerosolization and mucus penetration. Furthermore, these microparticles exhibited significantly enhanced permeability compared to raw tiotropium, leading to better therapeutic outcomes in the asthma-induced rat model.
Article
Pharmacology & Pharmacy
Taek Kwan Kwon, Ji-Hyun Kang, Sang-Beom Na, Jae Ho Kim, Yong-Il Kim, Dong-Wook Kim, Chun-Woong Park
Summary: The esomeprazole magnesium-loaded dual-release mini-tablet polycap (DR polycap) is a novel drug formulation with prolonged onset time and improved bioavailability, serving as an alternative to commercial products for preventing nocturnal acid breakthrough.
Article
Chemistry, Medicinal
Ji-Hyun Kang, Ji-Eun Lee, So-Jeong Jeong, Chun-Woong Park, Dong-Wook Kim, Kwon-Yeon Weon
Summary: This study aims to improve the solubility of rivaroxaban (RIV) and develop a formulation that can be conveniently administered regardless of the meal, ensuring reproducibility of efficacy. The results show that the developed R-C-P complex formulation has higher solubility and better release performance compared to commercial products.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2022)
Article
Pharmacology & Pharmacy
Chang-Soo Han, Ji-Hyun Kang, Eun Hye Park, Hyo-Jung Lee, So-Jeong Jeong, Dong-Wook Kim, Chun-Woong Park
Summary: Corrugated surface microparticles consisting of levofloxacin, chitosan, and organic acid were prepared to enhance the aerodynamic performance and aerosolization for lung drug delivery. The roughness of the microparticles was influenced by the amount and boiling point of the organic acid. The results demonstrated improved aerodynamic performance and aerosolization of the corrugated microparticles.
ASIAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Jae-Cheol Choi, Ji-Hyun Kang, Dong-Wook Kim, Chun-Woong Park
Summary: This study aimed to develop inhalable microparticles of amifostine using different methods (jet milling and wet ball milling) and solvents (methanol, ethanol, chloroform, and toluene), and compare their physicochemical properties and inhalation efficiency. Inhalable microparticles of amifostine were successfully prepared through a wet ball-milling process, using polar and non-polar solvents for improved pulmonary delivery.
Review
Pharmacology & Pharmacy
Min-Seok Yang, Ji-Hyun Kang, Dong-Wook Kim, Chun-Woong Park
JOURNAL OF PHARMACEUTICAL INVESTIGATION
(2023)
Article
Pharmacology & Pharmacy
Ji-Hyun Kang, Jae-Cheol Choi, Woo Yul Song, Jihoon Choi, Sung-Hoon Lee, Chun-Woong Park
Summary: Administration of pirfenidone (PRF) through the pulmonary route as dry powder inhaler showed superior bioavailability and therapeutic effect compared to oral route. Wet bead milling method was more efficient for preparing inhalable PRF microparticles.
JOURNAL OF PHARMACEUTICAL INVESTIGATION
(2023)
