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1.
Int Ophthalmol ; 44(1): 297, 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38951293

ABSTRACT

BACKGROUND/OBJECTIVES: To evaluate the effect of topical cyclosporine A (CsA) 0.05% in patients with pterygium surgery using fibrin glue (FG). SUBJECTS/METHODS: Patients with primary nasal pterygium were retrospectically analyzed and categorized into two groups: Group 1 with 41 eyes from 38 patients as a control group and group 2 with 39 eyes from 36 patients who received topical CsA twice a day for 6 months. Patients were assessed for recurrence rate, tear film parameters, side effects, and complications at postoperative intervals of 1-7 days; 1st, 3rd, 6th and 12th months. The follow-up period was 1 year. RESULTS: The two groups were age (p = 0.934) and sex (p = 0.996) matched. CsA drop was discontinued in one patient due to burning sensation and conjunctival hyperemia after 1 week. There was no statistically significant difference between the mean preoperative and postoperative 1st year Schirmer I and tear break-up time (TBUT) values in group 1 (p = 0.136; p = 0.069). Although the difference between the mean preoperative and postoperative 1st year TBUT values in group 2 was not statistically different (p = 0.249), Schirmer I results were higher postoperatively (p = 0.003). There was no statistically significant difference between preoperative Schirmer (p = 0.496), postoperative Schirmer (p = 0.661), preoperative TBUT (p = 0.240) and postoperative TBUT (p = 0.238) results of the two groups. Recurrence was observed in only one patient from group 1. CONCLUSION: No recurrent pterygium cases were observed in group 2. Schirmer I values were higher postoperatively in group 2; thus,topical CsA treatment may improve lacrimal secretion and be effective after pterygium surgery with FG.


Subject(s)
Cyclosporine , Fibrin Tissue Adhesive , Immunosuppressive Agents , Pterygium , Humans , Pterygium/surgery , Pterygium/diagnosis , Cyclosporine/administration & dosage , Male , Female , Middle Aged , Fibrin Tissue Adhesive/administration & dosage , Immunosuppressive Agents/administration & dosage , Retrospective Studies , Follow-Up Studies , Adult , Tissue Adhesives/administration & dosage , Tissue Adhesives/therapeutic use , Treatment Outcome , Aged , Ophthalmic Solutions/administration & dosage , Ophthalmologic Surgical Procedures/methods , Ophthalmologic Surgical Procedures/adverse effects , Recurrence , Conjunctiva , Tears/metabolism , Tears/physiology
2.
Yakugaku Zasshi ; 144(7): 775-779, 2024.
Article in English | MEDLINE | ID: mdl-38945852

ABSTRACT

Venetoclax (VEN) is used in patients with acute myeloid leukemia (AML) and is primarily metabolized by CYP3A4, a major drug-metabolizing enzyme. Patients with AML simultaneously administered VEN and CYP3A4 inhibitors require a more appropriate management of drug-drug interactions (DDIs). Here, we report two cases of patients with AML (54-year-old man and 22-year-old woman) administrated VEN and CYP3A4 inhibitors, such as posaconazole, cyclosporine, or danazol. In the first case, we evaluated the appropriateness of timing for adjusting VEN dosage subsequent to the cessation of posaconazole. Consequently, modifying the VEN dosage in conjunction with the cessation of Posaconazole simultaneously may result in elevated plasma VEN levels. In the second case, plasma VEN concentrations were markedly elevated when co-administered with several CYP3A4 inhibitors. Additionally, in vitro assays were conducted for reverse translational studies to analyze CYP3A4 inhibition. CYP3A4 inhibition by combinatorial administration of cyclosporine A and danazol was demonstrated in vitro, which potentially explains the increasing plasma VEN concentrations observed in clinical settings. Although the acquisition of therapeutic effects is a major priority for patients, frequent therapeutic drug monitoring and dosage adjustments considering DDIs would be important factors in chemotherapy.


Subject(s)
Bridged Bicyclo Compounds, Heterocyclic , Cytochrome P-450 CYP3A Inhibitors , Cytochrome P-450 CYP3A , Drug Interactions , Drug Monitoring , Leukemia, Myeloid, Acute , Sulfonamides , Humans , Sulfonamides/administration & dosage , Leukemia, Myeloid, Acute/drug therapy , Cytochrome P-450 CYP3A Inhibitors/administration & dosage , Male , Young Adult , Middle Aged , Bridged Bicyclo Compounds, Heterocyclic/administration & dosage , Bridged Bicyclo Compounds, Heterocyclic/pharmacokinetics , Bridged Bicyclo Compounds, Heterocyclic/blood , Female , Cytochrome P-450 CYP3A/metabolism , Cyclosporine/administration & dosage , Triazoles/administration & dosage , Antineoplastic Agents/administration & dosage
3.
Medicine (Baltimore) ; 103(25): e38616, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38905364

ABSTRACT

INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening syndrome for which early recognition and treatment are essential for improving outcomes. HLH is characterized by uncontrolled immune activation leading to fever, cytopenias, hepatosplenomegaly, coagulation abnormalities, and elevated typical markers. This condition can be genetic or secondary, with the latter often triggered by infections. Here, we present a unique case of HLH secondary to acute otitis media (AOM), a common ear infection. PATIENT CONCERNS: We describe a 4-year-old boy who initially presented with a high fever and otalgia, later diagnosed with bilateral AOM. Despite antibiotic treatment, his condition deteriorated. DIAGNOSIS: The patient fulfilled diagnostic criteria for HLH. INTERVENTIONS: Aggressive treatment by using combination therapy with immunoglobulins, intravenous steroids (dexamethasone), cyclosporine, and etoposide was performed. OUTCOMES: After 1 month of treatment, improvement in the otologic symptoms was observed, and hematological findings gradually improved and normalized. LESSIONS: The link between AOM and HLH may be associated with inflammatory responses and immunological mechanisms, highlighting the importance of considering HLH in severe infection cases. This case emphasizes the need for prompt diagnosis and management, especially in secondary HLH scenarios, to improve patient outcomes. It is imperative to be aware of the potential correlation between these 2 conditions, and healthcare professionals should consider the likelihood of HLH.


Subject(s)
Lymphohistiocytosis, Hemophagocytic , Otitis Media , Humans , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/etiology , Lymphohistiocytosis, Hemophagocytic/complications , Lymphohistiocytosis, Hemophagocytic/drug therapy , Male , Child, Preschool , Otitis Media/complications , Otitis Media/drug therapy , Acute Disease , Dexamethasone/therapeutic use , Dexamethasone/administration & dosage , Cyclosporine/therapeutic use , Cyclosporine/administration & dosage , Etoposide/therapeutic use , Etoposide/administration & dosage , Immunoglobulins, Intravenous/therapeutic use
4.
Clin Transl Sci ; 17(6): e13818, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38807449

ABSTRACT

A study to determine the impact of cyclosporine (Neoral), an inhibitor of P-gp, on the pharmacokinetics of pralsetinib (trade name GAVRETO®) was conducted in 15 healthy adult volunteers. A single 200 mg dose of pralsetinib was administered orally alone and in combination with cyclosporine with a 9-day washout between treatments. Co-administration with cyclosporine resulted in a clinically relevant increase in pralsetinib maximum plasma concentration (Cmax) and area under the plasma concentration-time curve extrapolated to infinity (AUC0-∞) with associated geometric mean ratios (GMRs) and 90% confidence intervals (CIs) of 148% (109, 201) and 181% (136, 241), respectively. These findings provide insight into concomitant dosing of pralsetinib with inhibitors of P-gp given the increases in pralsetinib exposure observed when administered with cyclosporine. Based on these results, co-administration of pralsetinib with P-gp inhibitors is not recommended. In the event that co-administration cannot be avoided, it is recommended that the dose of pralsetinib be reduced.


Subject(s)
Cyclosporine , Drug Interactions , Healthy Volunteers , Humans , Male , Adult , Cyclosporine/administration & dosage , Cyclosporine/pharmacokinetics , Female , Young Adult , Area Under Curve , Middle Aged , Administration, Oral , ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & inhibitors , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Dose-Response Relationship, Drug , Benzimidazoles/pharmacokinetics , Benzimidazoles/administration & dosage
5.
Dermatol Clin ; 42(3): 357-363, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38796267

ABSTRACT

Oral psoriasis therapies include both older traditional immunosuppressants, such as methotrexate, cyclosporine, and acitretin, as well as newer, more targeted agents, such as apremilast, deucravacitinib, and oral interleukin-23 receptor antagonists. Patients may prefer oral therapies to injectable therapies based on the route of administration. Both older and newer oral psoriasis therapies can be utilized effectively in the treatment of psoriasis. Here, we will review oral agents used in the treatment of psoriasis as well as provide commentary on their role in our current, evolving psoriasis treatment paradigm.


Subject(s)
Acitretin , Cyclosporine , Dermatologic Agents , Immunosuppressive Agents , Methotrexate , Psoriasis , Thalidomide , Humans , Psoriasis/drug therapy , Administration, Oral , Thalidomide/analogs & derivatives , Thalidomide/therapeutic use , Acitretin/therapeutic use , Acitretin/administration & dosage , Immunosuppressive Agents/therapeutic use , Methotrexate/therapeutic use , Methotrexate/administration & dosage , Cyclosporine/therapeutic use , Cyclosporine/administration & dosage , Dermatologic Agents/therapeutic use , Dermatologic Agents/administration & dosage , Piperidines/therapeutic use , Piperidines/administration & dosage , Pyrazoles/therapeutic use , Pyrimidines/therapeutic use , Pyrroles/therapeutic use , Pyrroles/administration & dosage , Antibodies, Monoclonal, Humanized/therapeutic use , Keratolytic Agents/therapeutic use , Indoles/therapeutic use , Nicotinic Acids/therapeutic use , Nicotinic Acids/administration & dosage , Antibodies, Monoclonal
6.
ACS Appl Mater Interfaces ; 16(21): 27040-27054, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38743443

ABSTRACT

Strong precorneal clearance mechanisms including reflex blink, constant tear drainage, and rapid mucus turnover constitute great challenges for eye drops for effective drug delivery to the ocular epithelium. In this study, cyclosporine A (CsA) for the treatment of dry eye disease (DED) was selected as the model drug. Two strategies, PEGylation for mucus penetration and cationization for potent cellular uptake, were combined to construct a novel CsA nanosuspension (NS@lipid-PEG/CKC) by coating nanoscale drug particles with a mixture of lipids, DSPE-PEG2000, and a cationic surfactant, cetalkonium chloride (CKC). NS@lipid-PEG/CKC with the mean size ∼173 nm and positive zeta potential ∼+40 mV showed promoted mucus penetration, good cytocompatibility, more cellular uptake, and prolonged precorneal retention without obvious ocular irritation. More importantly, NS@lipid-PEG/CKC recovered tear production and goblet cell density more efficiently than the commercial cationic nanoemulsion on a dry eye disease rat model. All results indicated that a combination of PEGylation and cationization might provide a promising strategy to coordinate mucus penetration and cellular uptake for enhanced drug delivery to the ocular epithelium for nanomedicine-based eye drops.


Subject(s)
Cyclosporine , Dry Eye Syndromes , Phospholipids , Polyethylene Glycols , Animals , Cyclosporine/chemistry , Cyclosporine/pharmacology , Cyclosporine/pharmacokinetics , Cyclosporine/administration & dosage , Polyethylene Glycols/chemistry , Rats , Dry Eye Syndromes/drug therapy , Dry Eye Syndromes/pathology , Phospholipids/chemistry , Rats, Sprague-Dawley , Nanoparticles/chemistry , Drug Delivery Systems , Cations/chemistry , Ophthalmic Solutions/chemistry , Ophthalmic Solutions/pharmacology , Humans , Male , Cornea/metabolism , Cornea/drug effects
7.
Ann Transplant ; 29: e942823, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38741362

ABSTRACT

BACKGROUND The association between forced expiratory volume in 1 second (FEV1) trajectory and mortality in bronchiolitis obliterans syndrome (BOS) is not well defined. Using long-term data from a prior clinical trial of inhaled liposomal cyclosporine A (L-CsA-I) for lung transplant patients with BOS, this study examined the association between longitudinal FEV1 change and mortality. MATERIAL AND METHODS We analyzed long-term data from a clinical trial which randomized 21 patients with BOS (³20% decrease in FEV1 from personal maximum) to receive L-CsA-I plus standard-of-care (n=11) or standard-of-care (SOC) alone (n=10) for 24 weeks. A joint statistical model, combining a linear mixed model for FEV1 change and Cox regression for mortality, was utilized to examine the overall association between FEV1 trajectory and mortality during follow-up. RESULTS The 21 trial participants (10 single, 11 double lung recipients) had a mean FEV1 of 1.7±0.6 Liters at randomization. Median follow-up post-randomization was 35 months. In joint model analysis, 1 percent FEV1 decline predicted 1.076-fold increased mortality risk (95% confidence interval: -0.998 to 1.160, p=0.058). FEV1 decline was reduced by 2.6% per year in L-CsA-I patients compared to SOC (p=0.210), and overall survival at 1/3/5 years was 91%/64%/27% vs 90%/20%/0% for L-CsA-I versus SOC, respectively (p=0.164). CONCLUSIONS In BOS patients, greater longitudinal FEV1 decline predicts increased mortality. Trends towards prolonged stabilization of FEV1 and improved survival were observed with L-CsA-I receipt. Further analyses will aid in evaluating the utility of FEV1 change as a survival predictor, having implications in BOS management and future trial design.


Subject(s)
Bronchiolitis Obliterans , Cyclosporine , Lung Transplantation , Humans , Bronchiolitis Obliterans/drug therapy , Bronchiolitis Obliterans/mortality , Bronchiolitis Obliterans/etiology , Bronchiolitis Obliterans/physiopathology , Male , Female , Forced Expiratory Volume , Middle Aged , Cyclosporine/administration & dosage , Cyclosporine/therapeutic use , Administration, Inhalation , Follow-Up Studies , Adult , Pilot Projects , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/therapeutic use , Liposomes , Standard of Care , Treatment Outcome , Bronchiolitis Obliterans Syndrome
8.
Vestn Oftalmol ; 140(2): 102-111, 2024.
Article in Russian | MEDLINE | ID: mdl-38742506

ABSTRACT

Dry eye disease (DED) is pathogenetically based on inflammation of the ocular surface. A step-by-step approach to DED treatment involves early initiation of anti-inflammatory therapy, including instillation of cyclosporine A (CsA). However, recommendations for the use of topical CsA in clinical practice are limited. This article presents an expert consensus on practical recommendations for the management of patients with DED, including indications, time of initiation and duration of CsA therapy, comparison of CsA forms currently registered in the Russian Federation, as well as issues of patient education.


Subject(s)
Cyclosporine , Emulsions , Humans , Administration, Ophthalmic , Cyclosporine/administration & dosage , Dry Eye Syndromes/drug therapy , Dry Eye Syndromes/etiology , Immunosuppressive Agents/administration & dosage , Ophthalmic Solutions/administration & dosage , Treatment Outcome , Xerophthalmia/etiology , Xerophthalmia/drug therapy , Xerophthalmia/diagnosis
9.
Nanomedicine (Lond) ; 19(12): 1035-1050, 2024.
Article in English | MEDLINE | ID: mdl-38686958

ABSTRACT

Background: To prepare ocular emulsions containing bipartitioned oil droplets to entrap cyclosporin A (0.05% w/w) and etodolac (0.2% w/w) by using castor, olive and silicon oils. Methods: The physicochemical characterizations of prepared emulsions were performed. The drug's biodistribution profiles and pharmacokinetic parameters from emulsions were checked using the ultraperformance liquid chromatography-tandem mass spectrometry method in the ocular tissues of the healthy rabbit eye model. Results: The emulsions displayed 365.13 ± 7.21 nm size and 26.45 ± 2.09 mV zeta potential. The ferrying of two drugs after releasing from emulsions occurred across corneal/conjunctival tissues to enter the vitreous and sclera following a single drop administration into the rabbit's eyes. Conclusion: The dual drug-loaded emulsions were more likely to produce synergistic anti-inflammatory activity for managing moderate-to-severe dry eye disease.


[Box: see text].


Subject(s)
Cyclosporine , Emulsions , Etodolac , Rabbits , Animals , Emulsions/chemistry , Cyclosporine/pharmacokinetics , Cyclosporine/administration & dosage , Cyclosporine/chemistry , Etodolac/chemistry , Tissue Distribution , Particle Size , Dry Eye Syndromes/drug therapy , Castor Oil/chemistry , Cations/chemistry , Silicone Oils/chemistry , Olive Oil/chemistry , Cornea/drug effects , Cornea/metabolism , Ophthalmic Solutions/chemistry , Humans , Drug Liberation
10.
Int J Pharm ; 657: 124141, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38677392

ABSTRACT

TPGS (D-α-tocopheryl polyethylene glycol 1000 succinate) polymeric micelles show interesting properties for ocular administration thanks to their solubilization capability, nanometric size and tissue penetration ability. However, micelles formulations are generally characterized by low viscosity, poor adhesion and very short retention time at the administration site. Therefore, the idea behind this work is the preparation and characterization of a crosslinked film based on xanthan gum that contains TPGS micelles and is capable of controlling their release. The system was loaded with melatonin and cyclosporin A, neuroprotective compounds to be delivered to the posterior eye segment. Citric acid and heating at different times and temperatures were exploited as crosslinking approach, giving the possibility to tune swelling, micelles release and drug release. The biocompatibility of the platform was confirmed by HET-CAM assay. Ex vivo studies on isolated porcine ocular tissues, conducted using Franz cells and two-photon microscopy, demonstrated the potential of the xanthan gum-based platform and enlightened micelles penetration mechanism. Finally, the sterilization step was approached, and a process to simultaneously crosslink and sterilize the platform was developed.


Subject(s)
Administration, Ophthalmic , Delayed-Action Preparations , Drug Liberation , Micelles , Neuroprotective Agents , Polysaccharides, Bacterial , Vitamin E , Polysaccharides, Bacterial/chemistry , Animals , Swine , Neuroprotective Agents/administration & dosage , Neuroprotective Agents/chemistry , Neuroprotective Agents/pharmacokinetics , Vitamin E/chemistry , Vitamin E/administration & dosage , Delayed-Action Preparations/chemistry , Cyclosporine/administration & dosage , Cyclosporine/chemistry , Melatonin/administration & dosage , Melatonin/chemistry , Melatonin/pharmacology , Melatonin/pharmacokinetics , Sterilization , Cross-Linking Reagents/chemistry , Drug Carriers/chemistry , Eye/drug effects , Eye/metabolism , Drug Delivery Systems/methods
11.
Biopharm Drug Dispos ; 45(3): 117-126, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38646776

ABSTRACT

This study aimed to control the oral absorption of cyclosporine A (CsA) with the use of a mucosal drug delivery system (mDDS). Mucopenetrating nanocarriers (MP/NCs) and mucoadhesive nanocarriers (MA/NCs) were prepared by flash nanoprecipitation employing polystyrene-block-poly(ethylene glycol) and polystyrene-block-poly(N,N-dimethyl aminoethyl methacrylate), respectively. Their particle distribution in the rat gastrointestinal tract were visualized by fluorescent imaging. Plasma concentrations were monitored after oral administration of CsA-loaded MP/NCs (MP/CsA) and MA/NCs (MA/CsA) to rats. MP/NCs and MA/NCs had a particle size below 200 nm and ζ-potentials of 4 and 40 mV, respectively. The results from in vitro experiments demonstrated mucopenetration of MP/NCs and mucoadhesion of MA/NCs. Confocal laser scanning microscopic images showed diffusion of MP/NCs in the gastrointestinal mucus towards epithelial cells and localization of MA/NCs on the surface of the gastrointestinal mucus layer. In a pH 6.8 solution, rapid and sustained release of CsA were observed for MP/CsA and MA/CsA, respectively. After oral dosing (10 mg-CsA/kg) to rats, amorphous CsA powder exhibited a time to maximum plasma concentration (Tmax) of 3.4 h, maximum plasma concentration (Cmax) of 0.12 µg/mL, and bioavailability of 0.7%. Compared with amorphous CsA powder, MP/CsA shortened Tmax by 1.1 to 2.3 h and increased the bioavailability by 43-fold to 30.1%, while MA/CsA prolonged Tmax by 3.4 to 6.8 h with Cmax and bioavailability of 0.65 µg/mL and 11.7%, respectively. These pharmacokinetic behaviors would be explained by their diffusion and release properties modulated by polymeric surface modification. The mDDS approach is a promising strategy for the pharmacokinetic control of orally administered CsA.


Subject(s)
Cyclosporine , Drug Delivery Systems , Rats, Sprague-Dawley , Animals , Cyclosporine/pharmacokinetics , Cyclosporine/administration & dosage , Male , Administration, Oral , Rats , Immunosuppressive Agents/pharmacokinetics , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/blood , Drug Carriers/chemistry , Intestinal Mucosa/metabolism , Nanoparticles/chemistry , Biological Availability , Particle Size
12.
AAPS PharmSciTech ; 25(5): 92, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38684590

ABSTRACT

PURPOSE: Dry eye syndrome (DES), arising from various etiologic factors, leads to tear film instability and ocular surface damage. Given its anti-inflammatory effects, cyclosporine A (CsA) has been widely used as a short-term treatment option for DES. However, poor bioavailability and solubility of CsA in aqueous phase make the development of a cyclosporine A-based eye drop for ocular topical application a huge challenge. METHODS: In this study, a novel strategy for preparing cyclosporine A-loaded silk fibroin nanoemulsion gel (CsA NBGs) was proposed to address these barriers. Additionally, the rheological properties, ocular irritation potential, tear elimination kinetics, and pharmacodynamics based on a rabbit dry eye model were investigated for the prepared CsA NBGs. Furthermore, the transcorneal mechanism across the ocular barrier was also investigated. RESULTS: The pharmacodynamics and pharmacokinetics of CsA NBGs exhibited superior performance compared to cyclosporine eye drops, leading to a significant enhancement in the bioavailability of CsA NBGs. Furthermore, our investigation into the transcorneal mechanism of CsA NBGs revealed their ability to be absorbed by corneal epithelial cells via the paracellular pathway. CONCLUSION: The CsA NBG formulation exhibits promising potential for intraocular drug delivery, enabling safe, effective, and controlled administration of hydrophobic drugs into the eye. Moreover, it enhances drug retention within the ocular tissues and improves systemic bioavailability, thereby demonstrating significant clinical translational prospects.


Subject(s)
Biological Availability , Cyclosporine , Dry Eye Syndromes , Fibroins , Gels , Ophthalmic Solutions , Rabbits , Animals , Fibroins/chemistry , Cyclosporine/administration & dosage , Cyclosporine/pharmacokinetics , Cyclosporine/chemistry , Dry Eye Syndromes/drug therapy , Ophthalmic Solutions/administration & dosage , Drug Delivery Systems/methods , Administration, Ophthalmic , Solubility , Male , Emulsions/chemistry , Cornea/metabolism , Cornea/drug effects , Disease Models, Animal
13.
ACS Nano ; 18(17): 11084-11102, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38632691

ABSTRACT

Dry eye disease (DED) affects a substantial worldwide population with increasing frequency. Current single-targeting DED management is severely hindered by the existence of an oxidative stress-inflammation vicious cycle and complicated intercellular crosstalk within the ocular microenvironment. Here, a nanozyme-based eye drop, namely nanoceria loading cyclosporin A (Cs@P/CeO2), is developed, which possesses long-term antioxidative and anti-inflammatory capacities due to its regenerative antioxidative activity and sustained release of cyclosporin A (CsA). In vitro studies showed that the dual-functional Cs@P/CeO2 not only inhibits cellular reactive oxygen species production, sequentially maintaining mitochondrial integrity, but also downregulates inflammatory processes and repolarizes macrophages. Moreover, using flow cytometric and single-cell sequencing data, the in vivo therapeutic effect of Cs@P/CeO2 was systemically demonstrated, which rebalances the immune-epithelial communication in the corneal microenvironment with less inflammatory macrophage polarization, restrained oxidative stress, and enhanced epithelium regeneration. Collectively, our data proved that the antioxidative and anti-inflammatory Cs@P/CeO2 may provide therapeutic insights into DED management.


Subject(s)
Cerium , Cyclosporine , Dry Eye Syndromes , Cerium/chemistry , Cerium/pharmacology , Cyclosporine/pharmacology , Cyclosporine/administration & dosage , Dry Eye Syndromes/drug therapy , Dry Eye Syndromes/pathology , Animals , Mice , Humans , Reactive Oxygen Species/metabolism , Oxidative Stress/drug effects , Nanoparticles/chemistry , Macrophages/drug effects , Macrophages/metabolism , Macrophages/immunology , Mice, Inbred C57BL , Antioxidants/pharmacology , Antioxidants/chemistry , Antioxidants/administration & dosage , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/administration & dosage , Drug Delivery Systems
15.
J Cataract Refract Surg ; 50(6): 644-650, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38334413

ABSTRACT

This is a pooled analysis from 2 phase III clinical trials investigating a water-free topical cyclosporine 0.1% for the treatment of moderate to severe dry eye. The analyses included 1162 patients: 35% with cataract, 20% with pseudophakia, and 45% without cataract. Demographics or baseline characteristics were comparable across groups except for age and vision. The cyclosporine-treated patients achieved large mean improvements from baseline by day 15: -3.7 in patients without cataract, -3.2 in patients with cataract, and -3.1 in pseudophakic patients. These improvements were statistically significantly higher compared with the respective vehicle groups. In the cataract subgroup, 59% of patients treated with cyclosporine achieved ≥3 grade improvements in corneal staining score, as early as day 15. The magnitude of the effect and early onset of action make this new cyclosporine solution a promising candidate for preoperative management of ocular surface in patients undergoing cataract surgery.


Subject(s)
Cyclosporine , Dry Eye Syndromes , Immunosuppressive Agents , Ophthalmic Solutions , Pseudophakia , Humans , Cyclosporine/administration & dosage , Dry Eye Syndromes/drug therapy , Ophthalmic Solutions/administration & dosage , Female , Male , Aged , Immunosuppressive Agents/administration & dosage , Pseudophakia/physiopathology , Cataract/complications , Middle Aged , Visual Acuity/physiology , Double-Blind Method , Administration, Topical , Treatment Outcome , Cornea
16.
J Am Pharm Assoc (2003) ; 64(3): 102016, 2024.
Article in English | MEDLINE | ID: mdl-38272309

ABSTRACT

BACKGROUND: This study aimed to describe a case of rhabdomyolysis and acute kidney injury potentiated by a drug-drug interaction (DDI) between cyclosporine, leflunomide, and rosuvastatin in a kidney transplant recipient. CASE SUMMARY: A 74-year-old male with end-stage kidney disease secondary to type 2 diabetes mellitus and hypertension received a deceased by cardiac death kidney transplant. The patient's medical history included coronary artery disease and hyperlipidemia for which he was receiving rosuvastatin 40 mg daily. Five months after transplant, the patient developed BK viremia, which required multiple changes in immunosuppression and resulted in the initiation of leflunomide and cyclosporine modified. The patient used multiple pharmacies and coupon cards that delayed the identification of the DDIs between leflunomide, cyclosporine, and rosuvastatin. Approximately, 13 months after transplant, the biopsy report of the patient's allograft kidney showed acute cellular rejection Banff IB, hypertensive changes, and transplant glomerulopathy. This prompted the patient to receive a 3-day course of methylprednisolone 250 mg intravenous at the outpatient infusion center. Two weeks later, the patient presented to the transplant clinic with lightheadedness, dizziness, weakness, fatigue, bilateral eye drainage, and a decrease in appetite and was admitted to the hospital for further workup. On admission, creatine kinase was 2080 IU/L with myoglobin of 7601 ng/mL. The patient's diagnosis was statin myopathy with possible rhabdomyolysis acute kidney injury. Likely contributing factors included cyclosporine, leflunomide, and rosuvastatin DDI and administration of high-dose methylprednisolone. PRACTICE IMPLICATIONS: This case demonstrates the importance of pharmacist involvement throughout all phases of care in a kidney transplant recipient.


Subject(s)
Acute Kidney Injury , Cyclosporine , Drug Interactions , Immunosuppressive Agents , Kidney Transplantation , Leflunomide , Pharmacists , Rhabdomyolysis , Rosuvastatin Calcium , Humans , Male , Rhabdomyolysis/chemically induced , Aged , Rosuvastatin Calcium/adverse effects , Rosuvastatin Calcium/administration & dosage , Cyclosporine/adverse effects , Cyclosporine/administration & dosage , Acute Kidney Injury/chemically induced , Leflunomide/therapeutic use , Leflunomide/adverse effects , Leflunomide/administration & dosage , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/administration & dosage , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Kidney Failure, Chronic/surgery
17.
Transplant Cell Ther ; 30(5): 536.e1-536.e13, 2024 May.
Article in English | MEDLINE | ID: mdl-38281592

ABSTRACT

In 2015, dual T cell depletion with antithymocyte globulin (ATG) and post-transplantation cyclophosphamide (PTCy) combined with cyclosporine A (CsA) replaced our prior institutional graft-versus-host disease (GVHD) prophylaxis regimen of 4.5 mg/kg ATG, CsA, and mycophenolate mofetil (MMF) (ATG-based) in 10/10 HLA-matched unrelated donor (MUD) peripheral blood allogeneic hematopoietic stem cell transplantation (allo-HCT). The initial ATG dose of 4.5 mg/kg [ATG(4.5)/PTCy] was reduced to 2 mg/kg [ATG(2)/PTCy] in 2018. This study compares the results obtained from 444 adults undergoing MUD allo-HCT at our institution who received ATG(4.5)/PTCy (n = 127) or ATG(2)/PTCy (n = 223) with those who received ATG-based prophylaxis without PTCy (n = 84). The rates of grade II-IV and grade III-IV acute GVHD (aGVHD) at day +100 and moderate/severe chronic GVHD (cGVHD) at 1 year were 35.7%, 21.6%, and 14.7%, respectively, in patients receiving ATG-based prophylaxis without PTCy; 16.5%, 4.9%, and 4.3% in patients receiving ATG(4.5)/PTCy; and 23.3% (P = .004), 8.0% (P < .001), and 14.1% (P =.006) in patients receiving ATG(2)/PTCy. One-year overall survival (OS), nonrelapse mortality (NRM), and GVHD-free relapse-free survival (GRFS) were 69.8%, 25.3%, and 52.0%, respectively, for patients receiving ATG-based prophylaxis without PTCy; 82.7%, 17.3%, and 59.8% for patients receiving ATG(4.5)/PTCy; and 78.3% (P = .446), 14.7% (P = 101), and 56.2% (P = .448) for patients receiving ATG(2)/PTCy. On univariate analyses, the use of ATG(2)/PTCy was associated with a lower risk of NRM (hazard ratio, .54; P = .023) compared with the use of ATG-based prophylaxis without PTCy. ATG(2)/PTCy prophylaxis effectively prevents GVHD and is associated with comparable relapse risk, OS, and GRFS as seen with ATG(4.5)/PTCy and ATG-based prophylaxis without PTCy.


Subject(s)
Antilymphocyte Serum , Cyclophosphamide , Cyclosporine , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Unrelated Donors , Humans , Antilymphocyte Serum/therapeutic use , Hematopoietic Stem Cell Transplantation/adverse effects , Middle Aged , Male , Female , Graft vs Host Disease/prevention & control , Cyclophosphamide/therapeutic use , Adult , Cyclosporine/therapeutic use , Cyclosporine/administration & dosage , Aged , Transplantation, Homologous , Immunosuppressive Agents/therapeutic use , Young Adult , Treatment Outcome , HLA Antigens/immunology , Adolescent , Retrospective Studies
19.
BMJ Paediatr Open ; 7(1)2023 08.
Article in English | MEDLINE | ID: mdl-37643815

ABSTRACT

OBJECTIVE: Improved understanding of cyclosporine A (CsA) pharmacokinetics in children undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT) is crucial for effective prevention of acute graft-versus-host disease and medication safety. The aim of this study was to establish a population pharmacokinetic (Pop-PK) model that could be used for individualised therapy to paediatric patients undergoing allo-HSCT in China. DESIGN, SETTING AND PARTICIPANTS: A retrospective analysis of 251 paediatric HSCT patients who received CsA intravenously in the early post transplantation period at Women and Children's Medical Center in Guangzhou was conducted. ANALYSIS MEASURES: The model building dataset from 176 children was used to develop and analyse the CsA Pop-Pk model by using the nonlinear mixed effect model method. The basic information was collected by the electronic medical record system. Genotype was analysed by matrix-assisted time-of-flight mass spectrometry. The stability and predictability of the final model were verified internally, and a validation dataset of 75 children was used for external validation. Monte Carlo simulation is used to adjust and optimise the initial dose of CsA in paediatric allo-HSCT patients. RESULTS: The typical values for clearance (CL) and volume of distribution ([Formula: see text]) were 14.47 L/hour and 2033.53 L, respectively. The body weight and haematocrit were identified as significant variables for V, while only body weight had an impact on CL. The simulation based on the final model suggests that paediatrics with HSCT required an appropriate intravenous dose of 5 mg/kg/day to reach the therapeutic trough concentration. CONCLUSIONS: The CsA Pop-PK model established in this study can quantitatively describe the factors influencing pharmacokinetic parameters and precisely predict the intrinsic exposure to CsA in children. In addition, our dosage simulation results can provide evidence for the personalised medications TRIAL REGISTRATION NUMBER: ChiCTR2000040561.


Subject(s)
Cyclosporine , Hematopoietic Stem Cell Transplantation , Child , Humans , Body Weight , Cyclosporine/administration & dosage , Cyclosporine/pharmacokinetics , East Asian People , Retrospective Studies
20.
Curr Eye Res ; 48(6): 557-563, 2023 06.
Article in English | MEDLINE | ID: mdl-36800492

ABSTRACT

PURPOSE: To compare effect of topical cyclosporine-A 0.05% (CsA) and chloroquine phosphate 0.03% (CHQ) as an adjunct to standard therapy in maintaining post-laser assisted in situ keratomileusis (LASIK) ocular surface stability. METHODS: Randomized controlled trial on 100 eyes undergoing femtosecond-LASIK randomized into three groups: 33 eyes in Group I (Standard Treatment group), 34 eyes in Group II (CsA group) and 33 eyes in Group III (CHQ group). Standard treatment included topical moxifloxacin, topical prednisolone and carboxymethyl cellulose. Group II received topical CsA 0.05% twice daily for three months and group III received topical CHQ 0.03% twice daily for three months in addition to standard treatment. Primary outcome measure was change in ocular surface disease index (OSDI) at 6 months. Secondary outcome measures were tear break up time (TBUT), Schirmer-I score, tear film osmolarity, tear film MMP-9 and visual acuity. Follow-up was performed at postoperative 1, 3 and 6 months. RESULTS: At 6 months, OSDI score, MMP-9, tear osmolarity, TBUT and Schirmer score were significantly better in both CsA and CHQ groups as compared with controls (p < 0.001). OSDI, Tear osmolarity, TBUT, MMP-9 levels were comparable in CsA and CHQ group (p > 0.05). In CsA group, tear film MMP-9 levels at 6 months were comparable to preoperative baseline (p = 0.09). There was no significant change in the Schirmer score from baseline in the CsA group; in addition, the Schirmer score was significantly better than the CHQ group at 6 months (p = 0.02). Visual acuity was comparable in all three groups. Adverse effects including burning sensation, stinging, pain and redness were reported by ten patients (CsA group- 3, CHQ group-7; p = 0.28). CONCLUSION: Both CsA and CHQ are useful adjuncts to standard therapy in maintaining ocular surface stability after refractive surgery. Cyclosporine A has more potent and sustained anti-inflammatory effect with less ocular irritative effects.


Subject(s)
Astigmatism , Chloroquine , Cyclosporine , Dry Eye Syndromes , Keratomileusis, Laser In Situ , Myopia , Humans , Cyclosporine/administration & dosage , Chloroquine/administration & dosage , Administration, Topical , Keratomileusis, Laser In Situ/adverse effects , Dry Eye Syndromes/drug therapy , Dry Eye Syndromes/etiology , Postoperative Complications , Anti-Inflammatory Agents/administration & dosage , Prospective Studies , Astigmatism/surgery , Myopia/surgery , Treatment Outcome , Male , Female , Adult
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