Displaying publications 41 - 60 of 77 in total

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  1. Fulltext IPNA clinical practice recommendations for the diagnosis and management of children with steroid-resistant nephrotic syndrome
    Trautmann A, Vivarelli M, Samuel S, Gipson D, Sinha A, Schaefer F, et al.
    Pediatr Nephrol, 2020 Aug;35(8):1529-1561.
    PMID: 32382828 DOI: 10.1007/s00467-020-04519-1
    Idiopathic nephrotic syndrome newly affects 1-3 per 100,000 children per year. Approximately 85% of cases show complete remission of proteinuria following glucocorticoid treatment. Patients who do not achieve complete remission within 4-6 weeks of glucocorticoid treatment have steroid-resistant nephrotic syndrome (SRNS). In 10-30% of steroid-resistant patients, mutations in podocyte-associated genes can be detected, whereas an undefined circulating factor of immune origin is assumed in the remaining ones. Diagnosis and management of SRNS is a great challenge due to its heterogeneous etiology, frequent lack of remission by further immunosuppressive treatment, and severe complications including the development of end-stage kidney disease and recurrence after renal transplantation. A team of experts including pediatric nephrologists and renal geneticists from the International Pediatric Nephrology Association (IPNA), a renal pathologist, and an adult nephrologist have now developed comprehensive clinical practice recommendations on the diagnosis and management of SRNS in children. The team performed a systematic literature review on 9 clinically relevant PICO (Patient or Population covered, Intervention, Comparator, Outcome) questions, formulated recommendations and formally graded them at a consensus meeting, with input from patient representatives and a dietician acting as external advisors and a voting panel of pediatric nephrologists. Research recommendations are also given.
    Matched MeSH terms: Immunosuppressive Agents/therapeutic use*
  2. A case of minimal change disease complicated by acute kidney injury in systemic lupus erythematosus
    Wong KW
    Saudi J Kidney Dis Transpl, 2014 Nov;25(6):1308-11.
    PMID: 25394457
    Matched MeSH terms: Immunosuppressive Agents/therapeutic use
  3. Recurrent spontaneous subdural hematoma secondary to immune thrombocytopenia in a patient with overlap syndrome
    Goh KG, Ong SG
    Lupus, 2015 Jan;24(1):90-3.
    PMID: 25305213 DOI: 10.1177/0961203314554248
    Patients with autoimmune connective tissue disease may manifest as overlap syndrome with features of systemic lupus erythematosus (SLE), systemic sclerosis, rheumatoid arthritis and myositis. Those presenting with active SLE can present with immune thrombocytopenia (IT) and may be complicated with subdural hematoma which, though rare, is potentially life-threatening. We report here a patient with overlap syndrome who had recurrent spontaneous subdural hematoma due to severe thrombocytopenia which did not respond to corticosteroids and azathioprine. Her platelet count became normal with three doses of low-dose intravenous cyclophosphamide (IV CYC) given at 3-weekly intervals. She remained in remission with maintenance therapy with azathioprine.
    Matched MeSH terms: Immunosuppressive Agents/therapeutic use
  4. Lingual myoclonus and neuropsychiatric lupus: a new association?
    Ong SG, Chua R
    Int J Rheum Dis, 2014 Jun;17(5):583-5.
    PMID: 24330407 DOI: 10.1111/1756-185X.12260
    Matched MeSH terms: Immunosuppressive Agents/therapeutic use
  5. Open label randomized controlled trial assessing the efficacy of mycophenolate sodium against other conventional immunosuppressive agents in active systemic lupus erythematosus patients without renal involvement
    Yahya F, Jasmin R, Ng CT, Cheah TE, Sockalingam S
    Int J Rheum Dis, 2013 Dec;16(6):724-30.
    PMID: 24119227 DOI: 10.1111/1756-185X.12179
    Mycophenolate is an immunosuppressive agent which has been used in systemic lupus erythematosus (SLE) patients who have failed conventional therapy. However, the use of mycophenolate sodium in extra-renal SLE involvement has yet to be established. This study aimed to assess the efficacy of mycophenolate sodium in extra-renal SLE.
    Matched MeSH terms: Immunosuppressive Agents/therapeutic use*
  6. Successful treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) in systemic lupus erythematosus (SLE) with oral cyclophosphamide
    Jasmin R, Sockalingam S, Shahrizaila N, Cheah TE, Zain AA, Goh KJ
    Lupus, 2012 Sep;21(10):1119-23.
    PMID: 22433918 DOI: 10.1177/0961203312440346
    Peripheral neuropathy is a known manifestation of systemic lupus erythematosus. However, the association of primary autoimmune inflammatory neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP) with SLE is uncommon. We report a 26-year-old man who simultaneously presented with severe CIDP and photosensitive rash, but was unresponsive to intravenous immunoglobulin infusion and continued to progress. He was found to have underlying SLE and improved with combined corticosteroid and immunosuppressive therapy with oral cyclophosphamide. CIDP with underlying SLE may be more resistant to conventional therapy with IVIG, requiring the addition of other immunosuppressive agents.
    Matched MeSH terms: Immunosuppressive Agents/therapeutic use*
  7. Fulltext Pemphigus vulgaris in a pregnant woman and her neonate
    Ibrahim SB, Yashodhara BM, Umakanth S, Kanagasabai S
    BMJ Case Rep, 2012;2012.
    PMID: 22744241 DOI: 10.1136/bcr.02.2012.5850
    A 23-year-old pregnant woman in her second trimester of pregnancy presented with blisters on the face, abdomen and the leg. Based on the clinical presentation and skin biopsy (histopathology and direct immunofluorescence) the diagnosis of pemphigus vulgaris was established. The child born to this patient also had similar skin lesions. The lesions in the mother and the child improved after treatment. The authors report a rare case of pemphigus vulgaris in a pregnant lady and neonatal pemphigus in her child, both of whom were treated successfully.
    Matched MeSH terms: Immunosuppressive Agents/therapeutic use
  8. Early course of inflammatory bowel disease in a population-based inception cohort study from 8 countries in Asia and Australia
    Ng SC, Zeng Z, Niewiadomski O, Tang W, Bell S, Kamm MA, et al.
    Gastroenterology, 2016 Jan;150(1):86-95.e3; quiz e13-4.
    PMID: 26385074 DOI: 10.1053/j.gastro.2015.09.005
    BACKGROUND & AIMS: The incidence of inflammatory bowel disease (IBD) is increasing in Asia, but little is known about disease progression in this region. The Asia-Pacific Crohn's and Colitis Epidemiology Study was initiated in 2011, enrolling subjects from 8 countries in Asia (China, Hong Kong, Indonesia, Sri Lanka, Macau, Malaysia, Singapore, and Thailand) and Australia. We present data from this ongoing study.
    METHODS: We collected data on 413 patients diagnosed with IBD (222 with ulcerative colitis [UC], 181 with Crohn's disease [CD], 10 with IBD unclassified; median age, 37 y) from 2011 through 2013. We analyzed the disease course and severity and mortality. Risks for medical and surgical therapies were assessed using Kaplan-Meier analysis.
    RESULTS: The cumulative probability that CD would change from inflammatory to stricturing or penetrating disease was 19.6%. The cumulative probabilities for use of immunosuppressants or anti-tumor necrosis factor agents were 58.9% and 12.0% for patients with CD, and 12.7% and 0.9% for patients with UC, respectively. Perianal CD was associated with an increased risk of anti-tumor necrosis factor therapy within 1 year of its diagnosis (hazard ratio, 2.97; 95% confidence interval, 1.09-8.09). The cumulative probabilities for surgery 1 year after diagnosis were 9.1% for patients with CD and 0.9% for patients with UC. Patients with CD and penetrating disease had a 7-fold increase for risk of surgery, compared with patients with inflammatory disease (hazard ratio, 7.67; 95% confidence interval, 3.93-14.96). The overall mortality for patients with IBD was 0.7%.
    CONCLUSIONS: In a prospective population-based study, we found that the early course of disease in patients with IBD in Asia was comparable with that of the West. Patients with CD frequently progress to complicated disease and have accelerated use of immunosuppressants. Few patients with early stage UC undergo surgery in Asia. Increasing our understanding of IBD progression in different populations can help optimize therapy and improve outcomes.
    KEYWORDS: ACCESS; Natural History; Risk Factor; Treatment
    Matched MeSH terms: Immunosuppressive Agents/therapeutic use
  9. Disseminated nocardiosis with bilateral intraocular involvement in a renal allograft patient
    Tan SY, Tan LH, Teo SM, Thiruventhiran T, Kamarulzaman A, Hoh HB
    Transplant Proc, 2000 Nov;32(7):1965-6.
    PMID: 11120022
    Matched MeSH terms: Immunosuppressive Agents/therapeutic use
  10. Autoimmune thrombocytopenia and neutropenia after autologous peripheral blood stem cell transplantation
    Wahid FS, Cheong SK, Sivagengei K
    Acta Haematol., 2002;107(4):237-8.
    PMID: 12053154
    Matched MeSH terms: Immunosuppressive Agents/therapeutic use
  11. Development of de novo HLA donor specific antibodies (HLA-DSA), HLA antibodies (HLA-Ab) and allograft rejection post blood transfusion in kidney transplant recipients
    Jalalonmuhali M, Carroll RP, Tsiopelas E, Clayton P, Coates PT
    Hum Immunol, 2020 Jul;81(7):323-329.
    PMID: 32327243 DOI: 10.1016/j.humimm.2020.04.002
    BACKGROUND: Blood transfusion during the post-operative period of kidney transplantation is common as part of a life-saving procedure, especially in the event of acute blood loss. However, there have been conflicting opinions since the pre-cyclosporine era. The risk of sensitization post-transfusion remains the main limiting factor following transfusion in kidney transplant recipients. Thus, the objective of this study is to assess the development of de novo HLA-DSA, HLA-Ab and allograft rejection post blood transfusion.

    METHODOLOGY: This is a retrospective cohort study recruiting all kidney transplant recipients in South Australia from January 2010 till December 2018. Following that, the incidence of blood transfusion within one week post-operatively were traced (transfusion group). The outcomes were compared with all other transplant recipients (non-transfusion group). Recipient's demographic, donor characteristics and immunological risk profiles were obtained from the transplant unit database, while the biopsy report, history of blood transfusion, latest serum creatinine and follow-up status was gathered from the electronic medical system (OASIS). The HLA-DSA and HLA-Ab results were collected from the NOMS database. Finally, the survival data were merged with the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry for South Australia recipients graft survival.

    RESULTS: A total of 699 patients were eligible for analysis. The mean age was 50.64 ± 13.23 years old. There were more elderly (>65 years old) and females who needed transfusion. The majority had glomerulonephritis as the primary disease. There was no statistical difference in donor characteristics, cold ischemic time and immunological risk between the transfusion and non-transfusion group. There was no difference in the development of de novo HLA-DSA, HLA-Ab and rejection episodes between the group and the results were consistent in a model adjusted for all potential confounders. Median graft survival in days between the transfusion vs non-transfusion group was 1845 IQR (961,2430) and 1250 IQR (672,2013).

    CONCLUSION: Blood transfusion under strong immunosuppressive cover within a one-week post-operative period is safe with no significant association with the development of de novo HLA-DSA, HLA-Ab or clinical rejection.

    Matched MeSH terms: Immunosuppressive Agents/therapeutic use*
  12. Fulltext A comparison of thrombotic thrombocytopenic purpura in an inception cohort of patients with and without systemic lupus erythematosus
    Letchumanan P, Ng HJ, Lee LH, Thumboo J
    Rheumatology (Oxford), 2009 Apr;48(4):399-403.
    PMID: 19202160 DOI: 10.1093/rheumatology/ken510
    To compare the clinical presentation, response to therapy and outcome of thrombotic thrombocytopenic purpura (TTP) in an inception cohort of patients with and without SLE.
    Matched MeSH terms: Immunosuppressive Agents/therapeutic use
  13. Pharmacogenotyping of CYP3A5 in predicting dose-adjusted trough levels of tacrolimus among Malaysian kidney-transplant patients
    Hamzah S, Teh LK, Siew JS, Ahmad G, Wong HS, Zakaria ZA, et al.
    Can J Physiol Pharmacol, 2014 Jan;92(1):50-7.
    PMID: 24383873 DOI: 10.1139/cjpp-2013-0128
    Tacrolimus (FK506) is a calcineurin inhibitor with a narrow therapeutic index that exhibits large interindividual variation. Seventy-eight kidney transplant patients treated with tacrolimus were recruited to study the correlation of dose adjusted trough level (level/dose; L/D) of tacrolimus with CYP3A5 and ABCB1 genotypes, as well as the mRNA copy number of ABCB1 in blood. Patients were genotyped for ABCB1 (C1236T, G2677T/A, and C3435T) and CYP3A5 (G6986A), while ABCB1 mRNA transcript copy number was determined by absolute quantification (real-time PCR) in 46 patients. CYP3A5*3 genotypes were found to be a good predictor of tacrolimus L/D in kidney-transplant patients. Significantly higher L/D was observed among non-expressors (2.85, 95%: 2.05-3.70 (ng·mL(-1))/(mg·kg(-1))) as compared with the expressors (1.15, 95%: 0.95-1.80 (ng·mL(-1))/(mg·kg(-1))) of CYP3A5 (Mann-Whitney U test; P < 0.001). No correlation was observed between L/D and the ABCB1 genotypes. A significant inverse correlation of blood ABCB1 mRNA level with L/D was demonstrated (Spearman's Rank Order correlation; P = 0.016, rs = -0.348). However, in multiple regression analysis, only CYP3A5*3 genotype groups were found to be significantly correlated with tacrolimus L/D (P < 0.001). These findings highlight the importance of CYP3A5*3 pharmacogenotyping among kidney-transplant patients treated with tacrolimus, and confirm the role of blood cell P-glycoprotein in influencing the L/D for tacrolimus.
    Matched MeSH terms: Immunosuppressive Agents/therapeutic use*
  14. A randomised double-blind, placebo-controlled trial of allogeneic umbilical cord-derived mesenchymal stem cell for lupus nephritis
    Deng D, Zhang P, Guo Y, Lim TO
    Ann Rheum Dis, 2017 Aug;76(8):1436-1439.
    PMID: 28478399 DOI: 10.1136/annrheumdis-2017-211073
    OBJECTIVE: We evaluate the efficacy of human umbilical cord-derived mesenchymal stem cell (hUC-MSC) for the treatment of lupus nephritis (LN). Previous reports showed hUC-MSC could have dramatic treatment effect.

    METHODS: Eighteen patients with WHO class III or IV LN were randomly assigned to hUC-MSC (dose 2×108 cells) or placebo. All patients received standard immunosuppressive treatment, which consisted of intravenous methylprednisolone and cyclophosphamide, followed by maintenance oral prednisolone and mycophenolate mofetil.

    RESULTS: Remission occurred in 9 of 12 patients (75%) in the hUC-MSC group and 5 of 6 patients (83%) in the placebo group. Remission was defined as stabilisation or improvement in renal function, reduction in urinary red cells and protein. A similar proportion of patients on hUC-MSC and placebo achieved complete remission. Improvements in serum albumin, complement, renal function, Systemic Lupus Erythematosus Disease Activity Index and British Isles Lupus Assessment Group scores were similar in both groups. One patient on placebo had a stroke and another had ascites. One patient on hUC-MSC had leucopenia, pneumonia and subcutaneous abscess and another died of severe pneumonia. The trial was abandoned after 18 patients were enrolled when it had become obvious it would not demonstrate a positive treatment effect.

    CONCLUSION: hUC-MSC has no apparent additional effect over and above standard immunosuppression.

    TRIAL REGISTRATION NUMBER: NCT01539902; Results.
    Matched MeSH terms: Immunosuppressive Agents/therapeutic use*
  15. Fulltext Nocardia kroppenstedtii: a rare pathogen isolated from the spinal vertebral abscess of a patient on long-term immunosuppressive therapy
    Tay ST, Wong PL, Chiu CK, Tang SN, Lee JL, Hamdan NW, et al.
    Eur Rev Med Pharmacol Sci, 2021 01;25(2):605-608.
    PMID: 33577013 DOI: 10.26355/eurrev_202101_24618
    OBJECTIVE: Nocardia kroppenstedtii was isolated from the spinal vertebral abscess of a 78-year-old patient presenting with mid-thoracic pain and bilateral lower limb weakness and numbness. The patient was on long-term immunosuppressive therapy with steroids for underlying autoimmune hemolytic anemia. Investigations showed a T5 pathological fracture and vertebra plana with the erosion of the superior and inferior endplates. There was evidence of paraspinal collection from the T4-T6 vertebrae with an extension into the spinal canal. Analysis of Nocardia 16S rRNA (99.9%, 1395/1396 nt) and secA1 gene (99.5%, 429/431 nt) fragments showed the highest sequence similarity with Nocardia kroppenstedtii type strain (DQ157924), and next with Nocardia farcinica (Z36936). The patient was treated with intravenous carbapenem and oral trimethoprim-sulfamethoxazole for four weeks, followed by another six months of oral trimethoprim-sulfamethoxazole. Despite the improvement of neurological deficits, the patient required assistive devices to ambulate at discharge. This study reports the first isolation of N. kroppenstedtii from the spinal vertebral abscess of a patient from Asia. Infections caused by N. kroppenstedtii may be underdiagnosed as the bacterium can be misidentified as N. farcinica in the absence of molecular tests in the clinical laboratory.
    Matched MeSH terms: Immunosuppressive Agents/therapeutic use
  16. Fulltext Systemic lupus erythematosus and melioidosis
    Che Rahim MJ, Mohammad N, Kamaruddin MI, Wan Ghazali WS
    BMJ Case Rep, 2019 Jul 01;12(7).
    PMID: 31266760 DOI: 10.1136/bcr-2019-229974
    We reported a case of a young female patient presented with sepsis and diagnosed with melioidosis and systemic lupus erythematosus (SLE) within the same admission. She presented with 1-week history of productive cough, progressive dyspnoea together with prolonged fever, arthralgia, rashes and oral ulcers. She had septicemic shock, respiratory failure requiring intubation and ventilation in intensive care unit and subsequently developed acute renal failure requiring haemodialysis. Antibiotics and immunosuppressive treatment including low-dose intravenous cyclophosphamide were commenced. She had a remarkable recovery and was discharged after 6 weeks. There was no evidence of active SLE or relapse of melioidosis during clinic follow-ups.
    Matched MeSH terms: Immunosuppressive Agents/therapeutic use
  17. Fulltext Exposure-effect relationship of mycophenolic acid and prednisolone in adult patients with lupus nephritis
    Abd Rahman AN, Tett SE, Abdul Gafor HA, McWhinney BC, Staatz CE
    Br J Clin Pharmacol, 2015 Nov;80(5):1064-75.
    PMID: 25959850 DOI: 10.1111/bcp.12678
    AIMS: The aim was to examine relationships between total and unbound mycophenolic acid (MPA) and prednisolone exposure and clinical outcomes in patients with lupus nephritis.
    METHODS: Six blood samples were drawn pre- and at 1, 2, 4, 6 and 8 h post-dose and total and unbound MPA and prednisolone pre-dose (C0 ), maximum concentration (Cmax ) and area under the concentration-time curve (AUC) were determined using non-compartmental analysis in 25 patients. The analyses evaluated drug exposures in relation to treatment response since starting MPA and drug-related adverse events.
    RESULTS: Dose-normalized AUC varied 10-, 8-, 7- and 19-fold for total MPA, unbound MPA, total prednisolone and unbound prednisolone, respectively. Median values (95% CI) of total MPA AUC(0,8 h) (21.5 [15.0, 42.0] vs. 11.2 [4.8, 30.0] mg l(-1) h, P= 0.048) and Cmax (11.9 [6.7, 26.3] vs. 6.1 [1.6, 9.2] mg l(-1) , P = 0.016) were significantly higher in responders than non-responders. Anaemia was significantly associated with higher total (37.8 [14.1, 77.5] vs. 18.5 [11.7, 32.7] mg l(-1) h, P = 0.038) and unbound MPA AUC(0,12 h) (751 [214, 830] vs. 227 [151, 389] mg l(-1) h, P = 0.004). Unbound prednisolone AUC(0,24 h) was significantly higher in patients with Cushingoid appearance (unbound: 1372 [1242, 1774] vs. 846 [528, 1049] nmol l(-1) h, P = 0.019) than in those without. Poorer treatment response was observed in patients with lowest tertile exposure to both total MPA and prednisolone as compared with patients with middle and higher tertile exposure (17% vs. 74%, P = 0.023).
    CONCLUSIONS: This study suggests a potential role for therapeutic drug monitoring in individualizing immunosuppressant therapy in patients with lupus nephritis.
    KEYWORDS: lupus nephritis; mycophenolic acid; pharmacodynamics; pharmacokinetics; prednisolone; treatment outcome
    Study site: Nephrology and SLE Clinics, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
    Matched MeSH terms: Immunosuppressive Agents/therapeutic use*
  18. Severe infections in systemic lupus erythematosus: disease pattern and predictors of infection-related mortality
    Teh CL, Wan SA, Ling GR
    Clin Rheumatol, 2018 Aug;37(8):2081-2086.
    PMID: 29667100 DOI: 10.1007/s10067-018-4102-6
    Infection is a major cause of morbidity and mortality among patients with systemic lupus erythematosus (SLE). To describe the pattern of serious infections in patients with SLE and to identify the predictors of infection-related mortality among SLE patients with serious infections, we prospectively studied all SLE patients who were hospitalized with infections in Sarawak General Hospital during 2011-2015. Demographic data, clinical features, and outcomes were collected. Cox regression analysis was carried out to determine the independent predictors of infection-related mortality. There were a total of 125 patients with 187 episodes of serious infections. Our patients were of multiethnic origins with female predominance (89.6%). Their mean age was 33.4 ± 14.2 years. The patients had a mean disease duration of 66.8 ± 74.0 months. The most common site of infection was pulmonary (37.9%), followed by septicemia (22.5%). Gram-negative organisms (38.2%) were the predominant isolates within the cohort. There were 21 deaths (11.2%) during the study period. Independent predictors of infection-related mortality among our cohort of SLE patients were flare of SLE (HR 3.98, CI 1.30-12.21) and the presence of bacteremia (HR 2.54, CI 0.98-6.59). Hydroxychloroquine was protective of mortality from serious infections (HR 9.26, CI 3.40-25.64). Pneumonia and Gram-negative organisms were the predominant pattern of infection in our SLE cohort. The presence of flare of SLE and bacteremia were independent prognostic predictors of infection-related mortality, whereas hydroxychloroquine was protective of infection-related mortality among SLE patients with serious infections.
    Matched MeSH terms: Immunosuppressive Agents/therapeutic use
  19. Eosinophilic granulomatosis with polyangiitis and mononeuritis multiplex responded to induction cyclophosphamide
    Mohammad N, Wan Ghazali WS
    BMJ Case Rep, 2017 May 27;2017.
    PMID: 28551593 DOI: 10.1136/bcr-2016-218252
    We report a case of 28-year-old Malay woman who initially presented with multiple joints pain with underlying poorly controlled asthma since her childhood. She was treated as seronegative arthritis. However, the involvement of joints, asthma and high-eosinophil counts raised suspicion of Churg-Strauss syndrome. This disease is undoubtedly rare in Malaysians or even in Asian populations. After appropriate therapy was delivered for the correct diagnosis her clinical condition improved. She is currently receiving maintenance treatment.
    Matched MeSH terms: Immunosuppressive Agents/therapeutic use*
  20. Development of improved dosing regimens for mycophenolate mofetil based on population pharmacokinetic analyses in adults with lupus nephritis
    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: Immunosuppressive Agents/therapeutic use
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