Research

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14 pages, 1396 KiB

Open AccessArticle

Association between Antihyperlipidemic Agent Use and Age-Related Macular Degeneration in Patients with Hyperlipidemia: A Population-Based Retrospective Cohort Study

by Chun-Hao Chen, Hsiu-Chen Lin, Hsiu-Li Lin, Joseph Jordan Keller and Li-Hsuan Wang

Biomedicines 2023, 11(6), 1508; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11061508 - 23 May 2023

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Abstract

Several studies have indicated that lipoproteins might contribute to the pathogenesis of age-related macular degeneration (AMD). In this population-based retrospective cohort study, patients with hyperlipidemia were divided into two groups (study groups I and II) based on whether or not they were receiving [...] Read more.

Several studies have indicated that lipoproteins might contribute to the pathogenesis of age-related macular degeneration (AMD). In this population-based retrospective cohort study, patients with hyperlipidemia were divided into two groups (study groups I and II) based on whether or not they were receiving antihyperlipidemic agents. The comparison group included patients without hyperlipidemia who were randomly selected and matched with study group II patients. A Cox proportional hazard model was used to evaluate the risk of AMD among the groups. Patients with hyperlipidemia receiving antihyperlipidemic agents (study group I, n = 15,482) had a significantly increased AMD risk (adjusted hazard ratio (HR) = 1.23, 95% confidence interval (CI) = 1.04–1.45) compared to those not receiving antihyperlipidemic agents (study group II, n = 15,482). However, with an increase in cumulative exposure, a reduced risk of AMD was observed in patients using a defined daily dose of more than 721, with an adjusted HR of 0.34 (95% CI = 0.22–0.53, p < 0.001). Additionally, the adjusted HR of AMD for study group II was 1.40 (95% CI = 1.20–1.63, p < 0.001) relative to the comparison group (n = 61,928). In conclusion, the study results indicated that patients with hyperlipidemia have a higher AMD risk than patients without hyperlipidemia. Furthermore, patients with hyperlipidemia who received antihyperlipidemic agents had a significantly increased AMD risk. However, a dose-dependent reduction in the risk of AMD was observed in patients with hyperlipidemia using statins or/and fibrates. Full article

(This article belongs to the Special Issue Pharmacokinetics of Biomedicines: Impact on Pre-clinical Development and Clinical Use)

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14 pages, 760 KiB

Open AccessArticle

Association between Food/UGT2B7 Polymorphisms and Pharmacokinetics/Pharmacodynamics Properties of Indapamide in Healthy Humans

by Banaz Abbas, Nagwa A. Sabri and Amal A. El-Khouly

Biomedicines 2023, 11(5), 1501; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11051501 - 22 May 2023

Cited by 2 | Viewed by 1299

Abstract

Indapamide is an effective and safe antihypertensive medication showing a beneficial effect in combination with other antihypertensive agents regarding morbidity and mortality. A comparative study was performed under fasting and fed conditions to investigate the effect of food and selected single nucleotide polymorphisms [...] Read more.

Indapamide is an effective and safe antihypertensive medication showing a beneficial effect in combination with other antihypertensive agents regarding morbidity and mortality. A comparative study was performed under fasting and fed conditions to investigate the effect of food and selected single nucleotide polymorphisms in the uridine diphosphate glucuronyl transferase (UGT2B7) gene on the pharmacokinetics and pharmacodynamics behavior of indapamide 1.5 mg sustained release. Forty-nine healthy volunteers aged 18–55 years were randomized into two groups; 25 volunteers were administered indapamide under fasting conditions and 24 under fed conditions. Genotyping of the UGT2B7 rs7438135 and rs11740316 was done before commencing the study using predesigned TaqMan assays. Results showed that food independently decreased the value of indapamide’ T_max by 5.5 h and increased the value of C_max by 8.7 ng/mL. On the other hand, all genetic variants of both UGT2B7 SNPs had no significant impact on the values of T_max, C_max, and AUC_0–t; however, it was found that rs11740316 variant AG was correlated with a 2.8 h lower MRT_inf. Finally, BMI positively correlated with longer MRT_inf. It was concluded that none of rs7438135, rs11740316, or food had a significant impact on the pharmacodynamic properties. Food had a modest impact on indapamide C_max and T_max values, while there were unremarkable differences in safety and efficacy. Full article

(This article belongs to the Special Issue Pharmacokinetics of Biomedicines: Impact on Pre-clinical Development and Clinical Use)

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26 pages, 708 KiB

Open AccessArticle

Gene Polymorphism of Biotransformation Enzymes and Ciprofloxacin Pharmacokinetics in Pediatric Patients with Cystic Fibrosis

by Sergey K. Zyryanov, Elena A. Ushkalova, Elena I. Kondratyeva, Olga I. Butranova and Yulia A. Kondakova

Biomedicines 2022, 10(5), 1050; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10051050 - 02 May 2022

Cited by 1 | Viewed by 2072

Abstract

(1) Background: Ciprofloxacin (CPF) is widely used for the treatment of cystic fibrosis, including pediatric patients, but its pharmacokinetics is poorly studied in this population. Optimal CPF dosing in pediatric patients may be affected by gene polymorphism of the enzymes involved in its [...] Read more.

(1) Background: Ciprofloxacin (CPF) is widely used for the treatment of cystic fibrosis, including pediatric patients, but its pharmacokinetics is poorly studied in this population. Optimal CPF dosing in pediatric patients may be affected by gene polymorphism of the enzymes involved in its biotransformation. (2) Materials and Methods: a two-center prospective non-randomized study of CPF pharmacokinetics with sequential enrollment of patients (n-33, mean age 9.03 years, male-33.36%), over a period from 2016 to 2021. All patients received tablets of the original CPF drug Cyprobay^® at a dose of 16.5 mg/kg to 28.80 mg/kg. Blood sampling schedule: 0 (before taking the drug), 1.5 h; 3.0 h; 4.5 h; 6.0 h; 7.5 h after the first dosing. CPF serum concentrations were analyzed by high performance liquid chromatography mass spectrometry. The genotype of biotransformation enzymes was studied using total DNA isolated from whole blood leukocytes by the standard method. (4) Results: a possible relationship between the CA genotype of the CYP2C9 gene (c.1075A > C), the GG genotype of the CYP2D6*4 gene (1846G > A), the AG genotype of the GSTP1 gene (c.313A > G), the GCLC* genotype 7/7 and the CPF concentration in plasma (increased value of the area under the concentration–time curve) was established. Conclusions: Gene polymorphism of biotransformation enzymes may affect ciprofloxacin pharmacokinetics in children. Full article

(This article belongs to the Special Issue Pharmacokinetics of Biomedicines: Impact on Pre-clinical Development and Clinical Use)

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Review

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45 pages, 1033 KiB

Open AccessReview

Pharmacokinetics of Antibacterial Agents in the Elderly: The Body of Evidence

by Olga I. Butranova, Elena A. Ushkalova, Sergey K. Zyryanov, Mikhail S. Chenkurov and Elena A. Baybulatova

Biomedicines 2023, 11(6), 1633; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11061633 - 04 Jun 2023

Cited by 3 | Viewed by 3174

Abstract

Infections are important factors contributing to the morbidity and mortality among elderly patients. High rates of consumption of antimicrobial agents by the elderly may result in increased risk of toxic reactions, deteriorating functions of various organs and systems and leading to the prolongation [...] Read more.

Infections are important factors contributing to the morbidity and mortality among elderly patients. High rates of consumption of antimicrobial agents by the elderly may result in increased risk of toxic reactions, deteriorating functions of various organs and systems and leading to the prolongation of hospital stay, admission to the intensive care unit, disability, and lethal outcome. Both safety and efficacy of antibiotics are determined by the values of their plasma concentrations, widely affected by physiologic and pathologic age-related changes specific for the elderly population. Drug absorption, distribution, metabolism, and excretion are altered in different extents depending on functional and morphological changes in the cardiovascular system, gastrointestinal tract, liver, and kidneys. Water and fat content, skeletal muscle mass, nutritional status, use of concomitant drugs are other determinants of pharmacokinetics changes observed in the elderly. The choice of a proper dosing regimen is essential to provide effective and safe antibiotic therapy in terms of attainment of certain pharmacodynamic targets. The objective of this review is to perform a structure of evidence on the age-related changes contributing to the alteration of pharmacokinetic parameters in the elderly. Full article

(This article belongs to the Special Issue Pharmacokinetics of Biomedicines: Impact on Pre-clinical Development and Clinical Use)

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18 pages, 6096 KiB

Open AccessReview

Pharmacokinetics of Biopharmaceuticals: Their Critical Role in Molecular Design

by Takuo Ogihara, Kenta Mizoi and Akiko Ishii-Watabe

Biomedicines 2023, 11(5), 1456; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11051456 - 16 May 2023

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Abstract

Biopharmaceuticals have developed rapidly in recent years due to the remarkable progress in gene recombination and cell culture technologies. Since the basic structure of biopharmaceuticals can be designed and modified, it is possible to control the duration of action and target specific tissues [...] Read more.

Biopharmaceuticals have developed rapidly in recent years due to the remarkable progress in gene recombination and cell culture technologies. Since the basic structure of biopharmaceuticals can be designed and modified, it is possible to control the duration of action and target specific tissues and cells by kinetic modification. Amino acid sequence modifications, albumin fusion proteins, polyethylene glycol (PEG) modifications, and fatty acid modifications have been utilized to modify the duration of action control and targeting. This review first describes the position of biopharmaceuticals, and then the kinetics (absorption, distribution, metabolism, elimination, and pharmacokinetics) of classical biopharmaceuticals and methods of drug quantification. The kinetic innovations of biopharmaceuticals are outlined, including insulin analog, antibody-related drugs (monoclonal antibodies, Fab analogs, Fc analogs, Fab-PEG conjugated proteins, antibody-drug conjugates, etc.), blood coagulation factors, interferons, and other related drugs. We hope that this review will be of use to many researchers interested in pharmaceuticals derived from biological components, and that it aids in their knowledge of the latest developments in this field. Full article

(This article belongs to the Special Issue Pharmacokinetics of Biomedicines: Impact on Pre-clinical Development and Clinical Use)

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44 pages, 1355 KiB

Open AccessReview

Developmental Pharmacokinetics of Antibiotics Used in Neonatal ICU: Focus on Preterm Infants

by Olga I. Butranova, Elena A. Ushkalova, Sergey K. Zyryanov and Mikhail S. Chenkurov

Biomedicines 2023, 11(3), 940; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11030940 - 17 Mar 2023

Cited by 5 | Viewed by 3319

Abstract

Neonatal Infections are among the most common reasons for admission to the intensive care unit. Neonatal sepsis (NS) significantly contributes to mortality rates. Empiric antibiotic therapy of NS recommended by current international guidelines includes benzylpenicillin, ampicillin/amoxicillin, and aminoglycosides (gentamicin). The rise of antibacterial [...] Read more.

Neonatal Infections are among the most common reasons for admission to the intensive care unit. Neonatal sepsis (NS) significantly contributes to mortality rates. Empiric antibiotic therapy of NS recommended by current international guidelines includes benzylpenicillin, ampicillin/amoxicillin, and aminoglycosides (gentamicin). The rise of antibacterial resistance precipitates the growth of the use of antibiotics of the Watch (second, third, and fourth generations of cephalosporines, carbapenems, macrolides, glycopeptides, rifamycins, fluoroquinolones) and Reserve groups (fifth generation of cephalosporines, oxazolidinones, lipoglycopeptides, fosfomycin), which are associated with a less clinical experience and higher risks of toxic reactions. A proper dosing regimen is essential for effective and safe antibiotic therapy, but its choice in neonates is complicated with high variability in the maturation of organ systems affecting drug absorption, distribution, metabolism, and excretion. Changes in antibiotic pharmacokinetic parameters result in altered efficacy and safety. Population pharmacokinetics can help to prognosis outcomes of antibiotic therapy, but it should be considered that the neonatal population is heterogeneous, and this heterogeneity is mainly determined by gestational and postnatal age. Preterm neonates are common in clinical practice, and due to the different physiology compared to the full terms, constitute a specific neonatal subpopulation. The objective of this review is to summarize the evidence about the developmental changes (specific for preterm and full-term infants, separately) of pharmacokinetic parameters of antibiotics used in neonatal intensive care units. Full article

(This article belongs to the Special Issue Pharmacokinetics of Biomedicines: Impact on Pre-clinical Development and Clinical Use)

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15 pages, 706 KiB

Open AccessReview

Candidate Genes Encoding Dopamine Receptors as Predictors of the Risk of Antipsychotic-Induced Parkinsonism and Tardive Dyskinesia in Schizophrenic Patients

by Elena E. Vaiman, Natalia A. Shnayder, Maxim A. Novitsky, Vera S. Dobrodeeva, Polina S. Goncharova, Elena N. Bochanova, Margarita R. Sapronova, Tatiana E. Popova, Alexey A. Tappakhov and Regina F. Nasyrova

Biomedicines 2021, 9(8), 879; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9080879 - 23 Jul 2021

Cited by 11 | Viewed by 2956

Abstract

(1) Introduction: Extrapyramidal disorders form the so-called extrapyramidal syndrome (EPS), which is characterized by the occurrence of motor disorders as a result of damage to the basal ganglia and the subcortical-thalamic connections. Often, this syndrome develops while taking medications, in particular antipsychotics (APs). [...] Read more.

(1) Introduction: Extrapyramidal disorders form the so-called extrapyramidal syndrome (EPS), which is characterized by the occurrence of motor disorders as a result of damage to the basal ganglia and the subcortical-thalamic connections. Often, this syndrome develops while taking medications, in particular antipsychotics (APs). (2) Purpose: To review studies of candidate genes encoding dopamine receptors as genetic predictors of development of AP-induced parkinsonism (AIP) and AP-induced tardive dyskinesia (AITD) in patients with schizophrenia. (3) Materials and Methods: A search was carried out for publications of PubMed, Web of Science, Springer, and e-Library databases by keywords and their combinations over the last 10 years. In addition, the review includes earlier publications of historical interest. Despite extensive searches of these commonly used databases and search terms, it cannot be ruled out that some publications were possibly missed. (4) Results: The review considers candidate genes encoding dopamine receptors involved in pharmacodynamics, including genes DRD1, DRD2, DRD3, and DRD4. We analyzed 18 genome-wide studies examining 37 genetic variations, including single nucleotide variants (SNVs)/polymorphisms of four candidate genes involved in the development of AIP and AITD in patients with schizophrenia. Among such a set of obtained results, only 14 positive associations were revealed: rs1799732 (141CIns/Del), rs1800497 (C/T), rs6275 (C/T), rs6275 (C/T) DRD2; rs167771 (G/A) DRD3 with AIP and rs4532 (A/G) DRD1, rs6277 (C/T), rs6275 (C/T), rs1800497 (C/T), rs1079597 (A/G), rs1799732 (141CIns/Del), rs1045280 (C/G) DRD2, rs6280 (C/T), rs905568 (C/G) DRD3 with AITD. However, at present, it should be recognized that there is no final or unique decision on the leading role of any particular SNVs/polymorphisms in the development of AIP and AITD. (5) Conclusion: Disclosure of genetic predictors of the development of AIP and AITD, as the most common neurological adverse drug reactions (ADRs) in the treatment of patients with psychiatric disorders, may provide a key to the development of a strategy for personalized prevention and treatment of the considered complication of AP therapy for schizophrenia in real clinical practice. Full article

(This article belongs to the Special Issue Pharmacokinetics of Biomedicines: Impact on Pre-clinical Development and Clinical Use)

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19 pages, 1269 KiB

Open AccessReview

Using Pharmacogenetics of Direct Oral Anticoagulants to Predict Changes in Their Pharmacokinetics and the Risk of Adverse Drug Reactions

by Natalia A. Shnayder, Marina M. Petrova, Pavel A. Shesternya, Alina V. Savinova, Elena N. Bochanova, Olga V. Zimnitskaya, Elena A. Pozhilenkova and Regina F. Nasyrova

Biomedicines 2021, 9(5), 451; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9050451 - 22 Apr 2021

Cited by 22 | Viewed by 4004

Abstract

Dabigatran, rivaroxaban, apixaban, and edoxaban are direct oral anticoagulants (DOACs) that are increasingly used worldwide. Taking into account their widespread use for the prevention of thromboembolism in cardiology, neurology, orthopedics, and coronavirus disease 2019 (COVID 19) as well as their different pharmacokinetics and [...] Read more.

Dabigatran, rivaroxaban, apixaban, and edoxaban are direct oral anticoagulants (DOACs) that are increasingly used worldwide. Taking into account their widespread use for the prevention of thromboembolism in cardiology, neurology, orthopedics, and coronavirus disease 2019 (COVID 19) as well as their different pharmacokinetics and pharmacogenetics dependence, it is critical to explore new opportunities for DOACs administration and predict their dosage when used as monotherapy or in combination with other drugs. In this review, we describe the details of the relative pharmacogenetics on the pharmacokinetics of DOACs as well as new data concerning the clinical characteristics that predetermine the needed dosage and the risk of adverse drug reactions (ADRs). The usefulness of genetic information before and shortly after the initiation of DOACs is also discussed. The reasons for particular attention to these issues are not only new genetic knowledge and genotyping possibilities, but also the risk of serious ADRs (primarily, gastrointestinal bleeding). Taking into account the effect of the carriership of single nucleotide variants (SNVs) of genes encoding biotransformation enzymes and DOACs metabolism, the use of these measures is important to predict changes in pharmacokinetics and the risk of ADRs in patients with a high risk of thromboembolism who receive anticoagulant therapy. Full article

(This article belongs to the Special Issue Pharmacokinetics of Biomedicines: Impact on Pre-clinical Development and Clinical Use)

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