Displaying publications 1 - 20 of 43 in total

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  1. Abd Rahman AN, Tett SE, Abdul Gafor HA, McWhinney BC, Staatz CE
    Eur J Drug Metab Pharmacokinet, 2017 Dec;42(6):993-1004.
    PMID: 28536776 DOI: 10.1007/s13318-017-0420-3
    BACKGROUND AND OBJECTIVE: Mycophenolic acid (MPA) provides effective treatment for lupus nephritis patients. Owing to its large pharmacokinetic variability, it is questionable whether standard fixed dose therapy can achieve optimal MPA exposure. The aim of this study was to develop a population pharmacokinetic model of MPA and its metabolite, 7-O-MPA-β-glucuronide (MPAG), to identify important covariate influences and better predict patient dosing requirements.
    METHODS: MPA and MPAG concentration-time profiles were collected from 25 patients receiving mycophenolate mofetil (MMF) with or without cyclosporine (CsA) co-therapy. Samples were collected pre-dose and at 1, 2, 4, 6 and 8 h post-dose on one or two occasions.
    RESULTS: A total of 225 and 226 concentration-time measurements of MPA and MPAG, respectively, were used to develop the model, utilizing NONMEM® software. A two-compartment model with first-order absorption and elimination for MPA and a one-compartment model with first-order elimination and enterohepatic circulation (EHC) for MPAG best described the data. Apparent clearance of MPAG (CL/F MPAG) significantly decreased with reducing renal function and extent of EHC was reduced with concomitant CsA use. Simulations using the final model showed that a 70-kg subject with a creatinine clearance of 90 mL/min receiving concomitant CsA would require 1.25 g of MMF twice daily while a similar subject who did not receive concomitant CsA would require 0.75 g twice daily to achieve a MPA area under the concentration-time curve from 0 to 12 h (AUC0-12) of 45 mg·h/L.
    CONCLUSION: A 'tiered' dosing approach considering patient renal function and CsA co-therapy, rather than a 'one dose fits all' approach, would help individualize MMF therapy in adult lupus nephritis patients to ensure more patients have optimal MPA exposure.
    Study site: Nephrology and Systemic Lupus Erythematosus (SLE) Clinics, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
    Matched MeSH terms: Cyclosporine/pharmacology
  2. Al-Bayaty, F.H., Al-Tay, B.O., Al-Kushali, S.S., Mahmmod, L.
    ASM Science Journal, 2009;3(1):45-50.
    MyJurnal
    A study was undertaken to estimate the histological changes of gingival enlargement induced by
    Cyclosporin A (CsA) and Nifedipine, separately and in combination. Twelve adult rabbits were divided equally into four main groups. The first group received 10 mg/kg/day Nifedipine, the second received 10 mg/kg/day CsA, and the third received a combination of 10 mg/kg /day Nifedipine and CsA by gastric feeding. The fourth was regarded as a control group. Animals were given the drugs from day 1 of the experiment until day 70. They were then sacrificed for histological purposes. Results showed increase in the thickness of the epithelium with keratosis and acanthosis, and also increased vascularity. Collagen fibres and fibroblasts at different rates in the three histological groups were observed. Significant alveolar bone resorption with increased marrow spaces filled with fatty tissue were found in the CsA group. Non-significant changes in the alveolar bone of the Nifedipine group while subsequent bone resorption and bone deposition were seen in the combination group. These changes could be due to the effect of both drugs. Significant changes in the gingiva and the alveolar bone were shown in the three experimental groups compared with the control group.
    Matched MeSH terms: Cyclosporine
  3. Albela H, Begum S, Leong KF
    J Dermatolog Treat, 2021 Mar 11.
    PMID: 33706651 DOI: 10.1080/09546634.2021.1899111
    Generalized Pustular Psoriasis (GPP) is a rare, severe, life-threatening form of psoriasis and accounts for up to 13.1% of all childhood psoriasis. Common first-line systemic treatment for pediatric patients with GPP include oral acitretin, cyclosporin and methotrexate which have varying efficacy and side effects but multiple interventions are often needed to induce remission and maintain long term control. Recently, the anti IL 17 A monoclonal antibody secukinumab have been shown to be effective in adult patients with GPP; however, there is lack of evidence of its usage in the pediatric population. We describe a case series of 4 pediatric patients with GPP who were treated with off-label use of secukinumab. All four patients had marked clearance and reduction in Generalized Pustular Psoriasis Area & Severity Score (GPPASI) within first 48 h of first injection with subsequent almost complete to complete clearance of skin lesions by 1 month follow up. In conclusion, secukinumab was found to be successful in inducing remission, with rapid clearance and maintaining remission, with or without combination with other systemic agents for pediatric GPP.
    Matched MeSH terms: Cyclosporine
  4. Albitar O, Ballouze R, Harun SN, Mohamed Noor DA, Sheikh Ghadzi SM
    J Clin Pharmacol, 2020 11;60(11):1474-1482.
    PMID: 32557653 DOI: 10.1002/jcph.1670
    Cyclosporine is a primary drug in transplant immunosuppression regimens. It has a narrow therapeutic index and variable pharmacokinetic behavior. This study aimed to develop a population pharmacokinetic model of cyclosporine in Malaysian renal transplant recipients as well as to evaluate the performances of different methodsfor handling missing doses. A total of 2804 concentrationts predose and 2 hours after doses were collected retrospectively from 113 renal transplant patients on cyclosporine in Penang General Hospital. Model structure and pharmacokinetic parameters were estimated using nonlinear mixed-effects modeling software. Missing doses were handled using different methods to evaluate their performance. Covariate analysis was performed using stepwise forward addition (P < .05) followed by backward elimination (P < .001). Prediction-corrected visual predictive check and sampling-importance resampling methods were used to validate the final model. A 1-compartment model with first-order absorption and elimination best fitted the data. All methods to handle missing doses performed well with the missing dose method being superior to other methods and thus was applied in the final model. Cyclosporine clearance (CL/F) was estimated as 15.1 L/h, and volume of distribution (V/F) was 108 L. Postoperative time, sex, and calcium channel blockers were identified as significant covariates on CL/F, whereas sex and cholesterol level were identified as significant covariates on V/F. This is the first population pharmacokinetic model developed in Malaysian renal transplant patients using a large sample with an evaluation of different methods to handle missing doses in less informative conventional therapeutic drug-monitoring data.
    Matched MeSH terms: Cyclosporine/blood; Cyclosporine/pharmacokinetics*; Cyclosporine/therapeutic use
  5. Ariffin H, Lum SH, Cheok SA, Shekhar K, Ariffin WA, Chan LL, et al.
    J Paediatr Child Health, 2005 Mar;41(3):136-9.
    PMID: 15790325
    To study the clinical presentation, therapy and outcome of children diagnosed with both primary and secondary haemophagocytic lymphohistiocytosis (HLH) at the University of Malaya Medical Centre.
    Matched MeSH terms: Cyclosporine/therapeutic use*
  6. Azizan NZ, Gangaram HB, Hussein SH
    Med J Malaysia, 2008 Mar;63(1):51-4.
    PMID: 18935734 MyJurnal
    Pyoderma gangrenosum (PG) is an uncommon, chronic, painful, ulcerative skin disease of unknown origin, often associated with systemic diseases including inflammatory bowel disease, rheumatoid arthritis; monoclonal gammopathy, hepatitis and myeloproliferative disorders. The mainstay of therapy for PG has been high-dose corticosteroids but not all patients have a favourable outcome. Other systemic agents have also been used such as cyclosporine, azathioprine, cyclophosphamide and tacrolimus. However, all these systemic therapies can be complicated by serious side effects. In this paper, we report a series of four patients with pyoderma gangrenosum treated successfully with topical cyclosporine. No side-effects were observed in any of the patients and there was minimal systemic absorption of the topical cyclosporine.
    Matched MeSH terms: Cyclosporine/administration & dosage*
  7. Bastion ML, Mohamad MH
    BMJ Case Rep, 2012;2012.
    PMID: 22914237 DOI: 10.1136/bcr-2012-006525
    To describe the rare presentation of sympathetic ophthalmia in a teenage girl with no previous known ocular injury.
    Matched MeSH terms: Cyclosporine/therapeutic use
  8. Chai PF, Lee WS, Brown RM, McPartland JL, Foster K, McKiernan PJ, et al.
    J Pediatr Gastroenterol Nutr, 2010 Mar;50(3):295-302.
    PMID: 20118802 DOI: 10.1097/MPG.0b013e3181bf0ef7
    Graft rejection and disease recurrence are well-recognized complications of liver transplantation (LT) for autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (AISC). We describe indications and outcome of LT for childhood AIH and AISC.
    Matched MeSH terms: Cyclosporine/therapeutic use
  9. Chang SH, Lim CS, Low TS, Chong HT, Tan SY
    Transplant Proc, 2001 12 26;33(7-8):3700-1.
    PMID: 11750577
    Matched MeSH terms: Cyclosporine/adverse effects*
  10. Chia TY, Sattar MA, Abdulla MH, Rathore HA, Ahmad Fu, Kaur G, et al.
    Ren Fail, 2013 Aug;35(7):978-88.
    PMID: 23822648 DOI: 10.3109/0886022X.2013.809563
    This study investigated the effects of tempol, a superoxide dismutase (SOD) mimetic and L-NAME, a nitric oxide (NO) synthase inhibitor on the renal function and hemodynamics in cyclosporine A (CsA) induced renal insufficiency rats. Male Sprague-Dawley rats were treated with either vehicle (C), tempol (T, 1 mmol/L in drinking fluid), L-NAME (L, 1 mmol/L in drinking fluid), CsA (Cs, 25 mg/kg/day via gavage), CsA plus tempol (TCs), CsA plus L-NAME (LCs) or CsA plus a combination of tempol and L-NAME (TLCs) for 21 consecutive days. At the end of treatment regimen, the renal responses to noradrenaline (NA), phenylephrine (PE), methoxamine and angiotensin II (Ang II) were determined. Cs and LCs rats had lower creatinine clearance (0.7 ± 0.1 and 0.6 ± 0.5 vs. 1.3 ± 0.2 mL/min/kg) and fractional excretion of sodium (0.12 ± 0.02 and 0.17 ± 0.01 vs. 0.67 ± 0.04%) but higher systolic blood pressure (145 ± 2 and 178 ± 4 vs. 116 ± 2) compared to the control (all p 
    Matched MeSH terms: Cyclosporine/pharmacology*
  11. Chong FW, Chakravarthi S, Nagaraja HS, Thanikachalam PM, Lee N
    Malays J Pathol, 2009 Jun;31(1):35-43.
    PMID: 19694312
    Cyclosporine A (CsA), a calcineurin inhibitor produced by the fungi Trichoderma polysporum and Cylindrocarpon lucidum, is an immunosuppressant prescribed in organ transplants to prevent rejection. Its adverse effect on renal dysfunction has limited its use in a clinical setting. Apigenin (4',5',7'-Trihydroxyflavone), a herbal extract, with anti-inflammatory and anti-tumour properties, has been investigated for properties to reverse this adverse effect. This research was conducted to establish a standard protocol for immunohistochemical estimation of Transforming Growth Factor beta (TGF-beta) expression, as an indicator of Cyclosporine A induced damage, and to observe whether apoptotic index and TGF-beta expression can be used to assess effects of Apigenin on CsA induced renal dysfunction. Six groups of 5 male Sprague-Dawley albino rats each were dosed once daily for 21 days, as follows: (1) negative control--oral corn oil, (2) positive control--Cyclosporine A (25 mg/kg), (3) Group 3--Apigenin (20 mg/kg), (4) Group 4--Cyclosporine A (25 mg/kg) +Apigenin (10 mg/kg), (5) Group 5--Cyclosporine A (25 mg/kg) +Apigenin (15 mg/kg) and (6) Group 6--Cyclosporine A (25 mg/kg) +Apigenin (20 mg/kg). Cyclosporine A was administered intra-peritoneally while Apigenin was given orally. The rat kidneys were harvested and examined microscopically to assess the apoptotic index, and stained by immunohistochemistry for multifunctioning polypeptide TGF-beta expression. A high apoptotic index and TGF-beta intensity was observed in the Cyclosporine A group. Apigenin significantly reduced the both apoptotic index and TGF-beta intensity. The apoptotic index correlated with TGF-beta intensity, especially in glomeruli. This study indicates that Cyclosporine A can enhance the TGF-beta expression in rat kidney, signifying accelerated apoptosis. TGF-beta and apoptotic index may be used to assess Apigenin and its effect on Cyclosporine A induced renal damage.
    Matched MeSH terms: Cyclosporine/toxicity*
  12. Choong, Yi Fong, Chaw, Su Hlaing, Aye, Aye Mya Min, Chee, Geap Tay, Lai, Choo Ong, Hany Ariffin
    Neurology Asia, 2015;20(3):275-281.
    MyJurnal
    Background & Objective: Posterior reversible encephalopathy syndrome (PRES) is associated with
    immunosuppressive agents used in children with haemato-oncological diseases. There are no reports
    to date from the South Asia and South East Asia region. We report a Malaysian tertiary centre case
    series of children with haemato-oncological disease who developed PRES. Methods: Retrospective
    study of children seen with haemato-oncology diseases seen at the University Malaya Medical Centre
    Kuala Lumpur who developed PRES from 2011 – 2013. Clinical details were obtained from medical
    records and brain neuroimaging was reviewed. Results: Five patients met the inclusion criteria. All
    5 patients had significant hypertension acutely or subacutely prior to neurology presentation. Four
    presented with acute seizures and the remainder 1 presented with encephalopathy.Three patients
    were on chemotherapy, 1 had renal impairment and 1 had prior immunosupression for bone marrow
    transplantation. A full recovery was seen in 4 patients and 1 patient had mild residual quadriplegia.
    Conclusion: Our case series expands the clinico-radiological spectrum of PRES in children with
    underlying haemato-oncological disorders. It is the first to show that prior cyclosporin intake as long
    as 2 months is a potential risk factor for PRES. Clinicians need to be vigilant for development of
    PRES and closely monitor the blood pressure in these children who are receiving or recently had
    immunosuppressive drugs and present with acute neurological symptoms.
    Matched MeSH terms: Cyclosporine
  13. Chow SK
    Asia Pac Allergy, 2012 Apr;2(2):149-60.
    PMID: 22701866 DOI: 10.5415/apallergy.2012.2.2.149
    This guideline is a result of a consensus reached during the 19th Asian-Australasian Regional Conference of Dermatology by the Asian Academy of Dermatology and Venereology Study Group in collaboration with the League of Asian Dermatological Societies in 2010. Urticaria has a profound impact on the quality of life in Asia and the need for effective treatment is required. In line with the EAACI/GA(2)LEN/EDF/WAO guideline for the management of urticaria the recommended first-line treatment is new generation, non-sedating H1-antihistamines. If standard dosing is ineffective, increasing the dosage up to four-fold is recommended. For patients who do not respond to a four-fold increase in dosage of non-sedating H1-antihistamines, it is recommended that therapies such as H2-antihistamine, leukotriene antagonist, and cyclosporine A should be added to the antihistamine treatment. In the choice of second-line treatment, both their costs and risk/benefit profiles are the most important considerations.
    Matched MeSH terms: Cyclosporine
  14. Damanhuri NS, Kumolosasi E, Omar MS, Razak AFA, Mansor AH
    Daru, 2021 Jun;29(1):13-22.
    PMID: 33405191 DOI: 10.1007/s40199-020-00377-2
    BACKGROUND: P-glycoprotein (P-gp) is an Adenosine triphosphate (ATP) dependent drug-efflux pump which is located abundantly in the stomach and protects the gut mucosa from xenobiotic.

    OBJECTIVE: The purpose of this study was to investigate the influence of P-gp modulation on the efficacy of treatment regimen.

    METHOD: P-gp modulation in rats was performed by using P-gp inducer (150 mg/kg rifampicin) and P-gp inhibitor (10 mg/kg cyclosporine A) for 14 days prior to be infected with Helicobacter pylori (H. pylori). The rats were further divided into groups, which were normal control, vehicle control, antibiotics and omeprazole, antibiotics only and omeprazole only for another 2 weeks of treatment. The ulcer formation and P-gp expression were determined by using macroscopic evaluation and western blot analysis, respectively.

    RESULTS: The highest P-gp expression was shown in the induced P-gp rats (2.00 ± 0.68) while the lowest P-gp expression was shown in the inhibited P-gp rats (0.45 ± 0.36) compared to the normal P-gp rats. In all groups, the rats which were infected with H. pylori, had a significant increase (p 

    Matched MeSH terms: Cyclosporine/pharmacology
  15. Eng HS, Mohamed Z, Calne R, Lang CC, Mohd MA, Seet WT, et al.
    Kidney Int, 2006 May;69(10):1858-64.
    PMID: 16612333
    Cyclosporine is a substrate of cytochrome P-450 3A (CYP3A) subfamily of enzymes and characterized by a narrow therapeutic range with wide interindividual variation in pharmacokinetics. A few single-nucleotide polymorphisms detected in CYP3A genes have been shown to correlate significantly with the CYP3A protein expression and activity. We therefore postulated that these polymorphisms could be responsible for some of the interindividual variation in cyclosporine pharmacokinetics. The objective of our study is to determine correlation if any between single-nucleotide polymorphisms of CYP3A5 and CYP3AP1 on cyclosporine dose requirement and concentration-to-dose ratio in renal allograft recipients. Cyclosporine-dependent renal allograft recipients were genotyped for CYP3A5 A6986G and CYP3AP1 G-44A. The cyclosporine dosages prescribed and the corresponding cyclosporine trough levels for each patient were recorded so that cyclosporine dose per weight (mg/kg/day) and concentration-to-dose ratio (C(0)/D, whereby C(0) is trough level and D is daily dose per weight) could be calculated. A total of 67 patients were recruited for our study. The dose requirement for 1, 3, and 6 months post-transplantation ranged 2.3-11.4, 1.0-9.0, and 1.4-7.2 mg/kg/day, respectively. Patients with *1*1*1*1 (n=5) CYP3A5- and CYP3AP1-linked genotypes needed higher dose of cyclosporine compared to patients with *1*3*1*3 (n = 27) and *3*3*3*3 (n = 33) linked genotypes in months 3 and 6 post-transplantation (P < 0.016). The identification of patients with *1*1*1*1 by CYP3A5 and CYP3AP1 genotyping may have a clinically significant and positive impact on patient outcome with reduced rejection rate by providing pretransplant pharmacogenetic information for optimization of cyclosporine A dosing.
    Matched MeSH terms: Cyclosporine/pharmacokinetics*; Cyclosporine/pharmacology
  16. Fan KS, Lim TO, Morad Z, Suleiman AB, Lei CC, Khairullah A
    Transplant Proc, 1995 Feb;27(1):1466-8.
    PMID: 7878944
    Matched MeSH terms: Cyclosporine/therapeutic use
  17. Goh BL, Jalil R, Koh SN, Chua CT, Tan SY
    Transplant Proc, 1998 Nov;30(7):3535-6.
    PMID: 9838548
    Matched MeSH terms: Cyclosporine/administration & dosage*; Cyclosporine/pharmacokinetics; Cyclosporine/therapeutic use
  18. Goh BL, Tan SY
    Transplant Proc, 1998 Nov;30(7):3594-5.
    PMID: 9838575
    Matched MeSH terms: Cyclosporine/therapeutic use
  19. Goh BL, Morad Z, Cheah PL, Chua CT, Tan SY
    Transplant Proc, 1998 Nov;30(7):3592-3.
    PMID: 9838574
    Matched MeSH terms: Cyclosporine/therapeutic use
  20. Gouda W, Alsaqabi F, Moshrif A, Abbas AS, Abdel-Aziz TM, Islam MA
    J Med Case Rep, 2021 Oct 07;15(1):497.
    PMID: 34620236 DOI: 10.1186/s13256-021-03072-1
    BACKGROUND: Macrophage activation syndrome is classified as a secondary form of hemophagocytic lymphohistiocytosis. It is a hyperinflammatory complication observed to be comorbid with a variety of autoimmune diseases, including adult-onset Still's disease and systemic juvenile idiopathic arthritis. Macrophage activation syndrome is less commonly detected in adult patients with systemic lupus erythematosus, which, if untreated, can be fatal, though determining the optimum treatment strategy is still a challenge.

    CASE PRESENTATION: Herein, we report a case of macrophage activation syndrome in a 33-year-old Egyptian female as an unusual complication of a systemic lupus erythematosus flare in adult patients. Our patient was initially treated with a combination of intravenous methylprednisolone pulse therapy and intravenous immunoglobulin therapy, which was followed by a course of oral prednisolone and oral cyclosporine with little response. Switching from oral prednisone to intravenous dexamethasone sodium phosphate showed a more favorable clinical and biochemical response.

    CONCLUSION: Macrophage activation syndrome is less commonly detected in adult patients with systemic lupus erythematosus. Our case demonstrates that dexamethasone sodium phosphate can be a successful alternative treatment for patients with systemic lupus erythematosus complicated by macrophage activation syndrome in whom the response to pulse methylprednisolone was inadequate to manage their illness, proving to be remarkably effective in a relatively short time frame.

    Matched MeSH terms: Cyclosporine/therapeutic use
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