Displaying publications 1 - 20 of 157 in total

Abstract:
Sort:
  1. Harry S, Lai LL, Nik Mustapha NR, Abdul Aziz YF, Vijayananthan A, Rahmat K, et al.
    Clin Gastroenterol Hepatol, 2020 04;18(4):945-953.e2.
    PMID: 31442603 DOI: 10.1016/j.cgh.2019.08.023
    BACKGROUND & AIMS: HepaFat-Scan is a magnetic resonance imaging-based method for quantification of hepatic steatosis by volumetric liver fat fraction (VLFF) measurement. We aimed to validate VLFF and to compare it with controlled attenuation parameter (CAP) for determination of hepatic steatosis grade in patients with NAFLD, using histopathology and stereologic analyses of biopsies as the reference standard.

    METHODS: We performed a prospective study of consecutive adults with NAFLD who were scheduled for a liver biopsy at a tertiary hospital in Malaysia. Patients underwent VLFF and CAP measurements on the same day as their liver biopsy. Histopathology analyses of liver biopsy specimens were reported according to the Nonalcoholic Steatohepatitis Clinical Research Network scoring system. Stereologic analysis was performed using grid-point counting method combined with the Delesse principle.

    RESULTS: We analyzed data from 97 patients (mean age 57.0 ± 10.1 years; 44.33% male; 91.8% obese; 95.9% centrally obese). Based on histopathology analysis, the area under receiver operating characteristic curve (AUROC) for VLFF in detection of steatosis grade ≥S2 was 0.92 and for CAP the AUROC was 0.65 (P < .001). Based on stereological analysis, the AUROC for VLFF for detection of steatosis grade ≥S2 was 0.92 and for CAP the AUROC was 0.63, (P = .002); for identification of steatosis grade S3, the AUROC for VLFF was 0.92 and for CAP the AUROC was 0.68 (P < .001).

    CONCLUSIONS: In a prospective study of patients with NAFLD undergoing liver biopsy analysis, we found VLFF to more accurately determine grade of hepatic steatosis than CAP.

    Matched MeSH terms: Area Under Curve
  2. Colin PJ, Allegaert K, Thomson AH, Touw DJ, Dolton M, de Hoog M, et al.
    Clin Pharmacokinet, 2019 06;58(6):767-780.
    PMID: 30656565 DOI: 10.1007/s40262-018-0727-5
    BACKGROUND AND OBJECTIVES: Uncertainty exists regarding the optimal dosing regimen for vancomycin in different patient populations, leading to a plethora of subgroup-specific pharmacokinetic models and derived dosing regimens. We aimed to investigate whether a single model for vancomycin could be developed based on a broad dataset covering the extremes of patient characteristics. Furthermore, as a benchmark for current dosing recommendations, we evaluated and optimised the expected vancomycin exposure throughout life and for specific patient subgroups.

    METHODS: A pooled population-pharmacokinetic model was built in NONMEM based on data from 14 different studies in different patient populations. Steady-state exposure was simulated and compared across patient subgroups for two US Food and Drug Administration/European Medicines Agency-approved drug labels and optimised doses were derived.

    RESULTS: The final model uses postmenstrual age, weight and serum creatinine as covariates. A 35-year-old, 70-kg patient with a serum creatinine level of 0.83 mg dL-1 (73.4 µmol L-1) has a V1, V2, CL and Q2 of 42.9 L, 41.7 L, 4.10 L h-1 and 3.22 L h-1. Clearance matures with age, reaching 50% of the maximal value (5.31 L h-1 70 kg-1) at 46.4 weeks postmenstrual age then declines with age to 50% at 61.6 years. Current dosing guidelines failed to achieve satisfactory steady-state exposure across patient subgroups. After optimisation, increased doses for the Food and Drug Administration label achieve consistent target attainment with minimal (± 20%) risk of under- and over-dosing across patient subgroups.

    CONCLUSIONS: A population model was developed that is useful for further development of age and kidney function-stratified dosing regimens of vancomycin and for individualisation of treatment through therapeutic drug monitoring and Bayesian forecasting.

    Matched MeSH terms: Area Under Curve
  3. Miao H, Hartman M, Verkooijen HM, Taib NA, Wong HS, Subramaniam S, et al.
    BMC Cancer, 2016 10 21;16(1):820.
    PMID: 27769212
    BACKGROUND: CancerMath is a set of web-based prognostic tools which predict nodal status and survival up to 15 years after diagnosis of breast cancer. This study validated its performance in a Southeast Asian setting.

    METHODS: Using Singapore Malaysia Hospital-Based Breast Cancer Registry, clinical information was retrieved from 7064 stage I to III breast cancer patients who were diagnosed between 1990 and 2011 and underwent surgery. Predicted and observed probabilities of positive nodes and survival were compared for each subgroup. Calibration was assessed by plotting observed value against predicted value for each decile of the predicted value. Discrimination was evaluated by area under a receiver operating characteristic curve (AUC) with 95 % confidence interval (CI).

    RESULTS: The median predicted probability of positive lymph nodes is 40.6 % which was lower than the observed 43.6 % (95 % CI, 42.5 %-44.8 %). The calibration plot showed underestimation for most of the groups. The AUC was 0.71 (95 % CI, 0.70-0.72). Cancermath predicted and observed overall survival probabilities were 87.3 % vs 83.4 % at 5 years after diagnosis and 75.3 % vs 70.4 % at 10 years after diagnosis. The difference was smaller for patients from Singapore, patients diagnosed more recently and patients with favorable tumor characteristics. Calibration plot also illustrated overprediction of survival for patients with poor prognosis. The AUC for 5-year and 10-year overall survival was 0.77 (95 % CI: 0.75-0.79) and 0.74 (95 % CI: 0.71-0.76).

    CONCLUSIONS: The discrimination and calibration of CancerMath were modest. The results suggest that clinical application of CancerMath should be limited to patients with better prognostic profile.

    Matched MeSH terms: Area Under Curve
  4. Chee KY, Ong KY, Mak CY, Yacob S, Yeo SC, Thrichelam N, et al.
    Asia Pac Psychiatry, 2017 Dec;9(4).
    PMID: 28326670 DOI: 10.1111/appy.12278
    INTRODUCTION: The objective of this study was to establish the psychometric properties of the AD8 Dementia Screening Interview in patients with Parkinson disease (PD) with or without cognitive impairment using the Montreal Cognitive Assessment Tool (MoCA) for comparison.

    METHODS: The AD8 was translated into Malay for Malay-speaking participants. A correlation analysis and a receiver operator characteristic curve were generated to establish the psychometric properties of the AD8 in relation to the MoCA.

    RESULTS: One hundred fifty patients and their caretakers completed the AD8 and MoCA. Using a cutoff score of 1/8, the AD8 had 81% sensitivity and 59% specificity for the detection of cognitive impairment in PD. With a cutoff score of 2/8, the AD8 had 83% specificity and 64% sensitivity. The area under the receiver operator characteristic curve was 80%, indicating good-to-excellent discriminative ability.

    DISCUSSION: These findings suggest that the AD8 can reliably differentiate between cognitively impaired and cognitively normal patients with PD and is a useful caregiver screening tool for PD.

    Matched MeSH terms: Area Under Curve
  5. Ng, C.G., Rusdi, A.R., Anne Yee, H.A.
    MyJurnal
    Objective: The aim of this study was to evaluate the validity and reliability of the Malay version of the Fagerstrom Test for Nicotine Dependence (FTND-M) based on a group of male staffs in the hospital. This study will also determine whether an abbreviated version of the FTND-M can be used as a screening tool for nicotine dependence. Method: 107 male staffs participated in the study. They were given the FTND-M and Malay version of Mini-International Neuropsychiatric Interview (M.I.N.I.)-L component. Their carbon monoxide level measured in their breath by using exhaled air. One week later, these participants were again given FTND-M. Results: The discriminatory ability of FTND-M was good with AUC 0.74 (P2 with the sensitivity of 70.1%, specificity of 70%, PPV of 79.7% and NPV of 58.3%. The FTND-M had moderate internal consistency with a Cronbach’s alpha of 0.67. The testretest reliability after 1 week was fair (Spearman’s rho=0.5, p)
    Matched MeSH terms: Area Under Curve
  6. Zain SM, Tan HL, Mohamed Z, Chan WK, Mahadeva S, Basu RC, et al.
    JGH Open, 2020 Dec;4(6):1155-1161.
    PMID: 33319051 DOI: 10.1002/jgh3.12414
    Background and Aim: Advanced fibrosis is the most important predictor of liver-related mortality in non-alcoholic fatty liver disease (NAFLD). The aim of this study was to compare the diagnostic performance of noninvasive scoring systems in identifying advanced fibrosis in a Malaysian NAFLD cohort and propose a simplified strategy for the management of NAFLD in a primary care setting.

    Methods: We enrolled and reviewed 122 biopsy-proven NAFLD patients. Advanced fibrosis was defined as fibrosis stages 3-4. Noninvasive assessments included aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, AST-to-platelet ratio index (APRI), AST/ALT ratio, diabetes (BARD) score, fibrosis-4 (FIB-4) score, and NAFLD fibrosis score.

    Results: FIB-4 score had the highest area under the receiver operating characteristic curve (AUROC) and negative predictive value (NPV) of 0.86 and 94.3%, respectively, for the diagnosis of advanced fibrosis. FIB-4 score 

    Matched MeSH terms: Area Under Curve
  7. Tang BH, Zhang JY, Allegaert K, Hao GX, Yao BF, Leroux S, et al.
    Clin Pharmacokinet, 2023 Aug;62(8):1105-1116.
    PMID: 37300630 DOI: 10.1007/s40262-023-01265-z
    BACKGROUND AND OBJECTIVE: High variability in vancomycin exposure in neonates requires advanced individualized dosing regimens. Achieving steady-state trough concentration (C0) and steady-state area-under-curve (AUC0-24) targets is important to optimize treatment. The objective was to evaluate whether machine learning (ML) can be used to predict these treatment targets to calculate optimal individual dosing regimens under intermittent administration conditions.

    METHODS: C0 were retrieved from a large neonatal vancomycin dataset. Individual estimates of AUC0-24 were obtained from Bayesian post hoc estimation. Various ML algorithms were used for model building to C0 and AUC0-24. An external dataset was used for predictive performance evaluation.

    RESULTS: Before starting treatment, C0 can be predicted a priori using the Catboost-based C0-ML model combined with dosing regimen and nine covariates. External validation results showed a 42.5% improvement in prediction accuracy by using the ML model compared with the population pharmacokinetic model. The virtual trial showed that using the ML optimized dose; 80.3% of the virtual neonates achieved the pharmacodynamic target (C0 in the range of 10-20 mg/L), much higher than the international standard dose (37.7-61.5%). Once therapeutic drug monitoring (TDM) measurements (C0) in patients have been obtained, AUC0-24 can be further predicted using the Catboost-based AUC-ML model combined with C0 and nine covariates. External validation results showed that the AUC-ML model can achieve an prediction accuracy of 80.3%.

    CONCLUSION: C0-based and AUC0-24-based ML models were developed accurately and precisely. These can be used for individual dose recommendations of vancomycin in neonates before treatment and dose revision after the first TDM result is obtained, respectively.

    Matched MeSH terms: Area Under Curve
  8. Roberts MS, Gafni RI, Brillante B, Guthrie LC, Streit J, Gash D, et al.
    J. Bone Miner. Res., 2019 09;34(9):1609-1618.
    PMID: 31063613 DOI: 10.1002/jbmr.3747
    Autosomal dominant hypocalcemia type 1 (ADH1) is a rare form of hypoparathyroidism caused by heterozygous, gain-of-function mutations of the calcium-sensing receptor gene (CAR). Individuals are hypocalcemic with inappropriately low parathyroid hormone (PTH) secretion and relative hypercalciuria. Calcilytics are negative allosteric modulators of the extracellular calcium receptor (CaR) and therefore may have therapeutic benefits in ADH1. Five adults with ADH1 due to four distinct CAR mutations received escalating doses of the calcilytic compound NPSP795 (SHP635) on 3 consecutive days. Pharmacokinetics, pharmacodynamics, efficacy, and safety were assessed. Parallel in vitro testing with subject CaR mutations assessed the effects of NPSP795 on cytoplasmic calcium concentrations (Ca2+i ), and ERK and p38MAPK phosphorylation. These effects were correlated with clinical responses to administration of NPSP795. NPSP795 increased plasma PTH levels in a concentration-dependent manner up to 129% above baseline (p = 0.013) at the highest exposure levels. Fractional excretion of calcium (FECa) trended down but not significantly so. Blood ionized calcium levels remained stable during NPSP795 infusion despite fasting, no calcitriol supplementation, and little calcium supplementation. NPSP795 was generally safe and well-tolerated. There was significant variability in response clinically across genotypes. In vitro, all mutant CaRs were half-maximally activated (EC50 ) at lower concentrations of extracellular calcium (Ca2+o ) compared to wild-type (WT) CaR; NPSP795 exposure increased the EC50 for all CaR activity readouts. However, the in vitro responses to NPSP795 did not correlate with any clinical parameters. NPSP795 increased plasma PTH levels in subjects with ADH1 in a dose-dependent manner, and thus, serves as proof-of-concept that calcilytics could be an effective treatment for ADH1. Albeit all mutations appear to be activating at the CaR, in vitro observations were not predictive of the in vivo phenotype or the response to calcilytics, suggesting that other parameters impact the response to the drug. © 2019 American Society for Bone and Mineral Research.
    Matched MeSH terms: Area Under Curve
  9. Navaratnam V, Ramanathan S, Wahab MS, Siew Hua G, Mansor SM, Kiechel JR, et al.
    Eur J Clin Pharmacol, 2009 Aug;65(8):809-21.
    PMID: 19404632 DOI: 10.1007/s00228-009-0656-1
    There is limited pharmacokinetic data available for the combination artesunate + amodiaquine, which is used widely to treat uncomplicated malaria. This study examines the bioavailability and tolerability of a fixed (200 mg artesunate + 540 mg amodiaquine) and loose (200 mg + 612 mg) combination with a 2x2 cross-over design in 24 healthy volunteers.
    Matched MeSH terms: Area Under Curve
  10. Liu Y, Chapple V, Roberts P, Ali J, Matson P
    Reprod Biol, 2014 Dec;14(4):249-56.
    PMID: 25454490 DOI: 10.1016/j.repbio.2014.08.003
    A total of 341 fertilized and 37 unfertilized oocytes from 63 intracytoplasmic sperm injection (ICSI) treatment cycles were included for retrospective assessment using the Embryoscope time-lapse video system. The second polar body (pb2) extrusion occurred at 2.9±0.1 h (range 0.70-10.15 h) relative to sperm injection. All oocytes reduced in size following sperm injection (p<0.05) with shrinkage ceasing after 2h in the unfertilized and at pb2 extrusion in the fertilized oocytes. Pb2 extrusion was significantly delayed for women aged >38 years compared to those <35 years (3.4±0.2 vs. 2.8±0.1, p<0.01) or 35-38 years (3.4±0.2 vs. 2.8±0.1, p<0.01), but timing was not related to the Day 3 morphological grades (1-4) of subsequent embryos (2.9±0.1, 2.9±0.1, 2.8±0.2 and 3.0±0.1; p>0.05 respectively). A shorter time of first cleavage division relative to either sperm injection or pb2 extrusion is associated with both top grade (AUC=0.596 or 0.601, p=0.006 or 0.004) and usable embryos (AUC=0.638 or 0.632, p=0.000 respectively) on Day 3. In summary, (i) pb2 of human oocytes extrudes at various times following sperm injection, (ii) the timing of pb2 extrusion is significantly delayed when female age >38 years, but not related to subsequent embryo development, (iii) all human oocytes reduce in size following sperm injection, (iv) completion of pb2 extrusion in the fertilized oocytes is a pivotal event in terminating shrinkage of the vitellus, and (v) time to first cleavage division either from sperm injection or pb2 extrusion is a significant predictive marker for embryo quality on Day 3.
    Matched MeSH terms: Area Under Curve
  11. Liew KB, Peh KK, Loh GO, Tan YT
    Drug Dev Ind Pharm, 2014 Sep;40(9):1156-62.
    PMID: 23688276 DOI: 10.3109/03639045.2013.798805
    Although the general pharmacokinetics of cephalexin is quite established up-to-date, however, no population-based study on Cephalexin pharmacokinetics profile in Malay population has been reported yet in the literature.
    Matched MeSH terms: Area Under Curve
  12. Venkata Srikanth M, Songa AS, Nali SR, Battu JR, Kolapalli VR
    Drug Dev Ind Pharm, 2014 Jan;40(1):33-45.
    PMID: 23317339 DOI: 10.3109/03639045.2012.744416
    The objective of the present investigation was to study the applicability of thermal sintering technique for the development of gastric floating tablets of propranolol HCl. Formulations were prepared using four independent variables, namely (i) polymer quantity, (ii) sodium bicarbonate concentration, (iii) sintering temperature and (iv) sintering time. Floating lag time and t95 were taken as dependent variables. Tablets were prepared by the direct compression method and were evaluated for physicochemical properties, in vitro buoyancy and dissolution studies. From the drug release studies, it was observed that drug retarding property mainly depends upon the sintering temperature and time of exposure. The statistically optimized formulation (PTSso) was characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry studies, and no significant chemical interaction between drug and polymer was observed. Optimized formulation was stable at accelerated conditions for a period of six months. PTSso was evaluated for in vivo buoyancy studies in humans for both fed and fasted states and found that gastric residence time of the floating tablets were enhanced by fed stage but not in fasted state. Optimized formulation PTSso and commercial formulation Ciplar LA 80 were subjected to bioavailability studies in healthy human volunteers by estimating pharmacokinetic parameters such as Cmax, Tmax, area under curve (AUC), elimination rate constant (Kel), biological half-life (t1/2) and mean residence time (MRT). There was a significant increase in the bioavailability of the propranolol HCl from PTSso formulation, which was evident from increased AUC levels and larger MRT values than Ciplar LA 80.
    Matched MeSH terms: Area Under Curve
  13. Subramaniam S, Chan CY, Soelaiman IN, Mohamed N, Muhammad N, Ahmad F, et al.
    Arch Osteoporos, 2019 11 28;14(1):117.
    PMID: 31781876 DOI: 10.1007/s11657-019-0666-2
    The concordance between osteoporosis self-assessment tool for Asians (OSTA) and dual-energy X-ray absorptiometry (DXA) was fair in the study. Modification of OSTA cutoff values improved its sensitivity to identify subjects at risk for suboptimal bone health (osteopenia/osteoporosis) and osteoporosis.

    PURPOSE: Osteoporosis self-assessment tool for Asians (OSTA) is a convenient screening algorithm used widely to identify patients at risk of osteoporosis. Currently, the number of studies validating OSTA in Malaysian population is limited. This study aimed to validate the performance of OSTA in identifying subjects with osteoporosis determined with DXA.

    METHODS: This cross-sectional study recruited 786 Malaysians in Klang Valley, Malaysia. Their bone health status was assessed by DXA and OSTA. The association and agreement between OSTA and bone mineral density assessment by DXA were determined by Pearson's correlation and Cohen's kappa, respectively. Receiver operating characteristics (ROC) curves were used to determine the sensitivity, specificity, and area under the curve (AUC) for OSTA.

    RESULTS: OSTA and DXA showed a fair association in the study (r = 0.382, κ = 0.159, p 

    Matched MeSH terms: Area Under Curve
  14. Daud NM, Ismail NA, Thomas EL, Fitzpatrick JA, Bell JD, Swann JR, et al.
    Obesity (Silver Spring), 2014 Jun;22(6):1430-8.
    PMID: 24715424 DOI: 10.1002/oby.20754
    OBJECTIVE: To investigate the effect of nutrient stimulation of gut hormones by oligofructose supplementation on appetite, energy intake (EI), body weight (BW) and adiposity in overweight and obese volunteers.

    METHODS: In a parallel, single-blind and placebo-controlled study, 22 healthy overweight and obese volunteers were randomly allocated to receive 30 g day(-1) oligofructose or cellulose for 6 weeks following a 2-week run-in. Subjective appetite and side effect scores, breath hydrogen, serum short chain fatty acids (SCFAs), plasma gut hormones, glucose and insulin concentrations, EI, BW and adiposity were quantified at baseline and post-supplementation.

    RESULTS: Oligofructose increased breath hydrogen (P area under the curve (tAUC)420 mins peptide YY (PYY) (P = 0.056) and reduced tAUC450 mins hunger (P = 0.034) and motivation to eat (P = 0.013) when compared with cellulose. However, there was no significant difference between the groups in other parameters although within group analyses showed an increase in glucagon-like peptide 1 (GLP-1) (P = 0.006) in the cellulose group and a decrease in EI during ad libitum meal in both groups.

    CONCLUSIONS: Oligofructose increased plasma PYY concentrations and suppressed appetite, while cellulose increased GLP-1 concentrations. EI decreased in both groups. However, these positive effects did not translate into changes in BW or adiposity.

    Matched MeSH terms: Area Under Curve
  15. Ahmad SY, Friel JK, MacKay DS
    PMID: 31697573 DOI: 10.1139/apnm-2019-0359
    BACKGROUND: This study aims to determine the effect of pure forms of sucralose and aspartame, in doses reflective of common consumption, on glucose metabolism.

    METHODS: Healthy participants consumed pure forms of a non-nutritive sweetener (NNS) mixed with water that were standardized to doses of 14% (0.425 g) of the acceptable daily intake (ADI) for aspartame and 20% (0.136 g) of the ADI for sucralose every day for two weeks. Blood samples were collected and analysed for glucose, insulin, active glucagon-like peptide-1 (GLP-1), and leptin.

    RESULTS: Seventeen participants (10 females and 7 males; age 24 ± 6.8 years; BMI 22.9 ± 2.5 kg/m2) participated in the study. The total area under the curve (AUC) values of glucose, insulin, active GLP-1 and leptin were similar for the aspartame and sucralose treatment groups compared to the baseline values in healthy participants. There was no change in insulin sensitivity after NNS treatment compared to the baseline values.

    CONCLUSIONS: These findings suggest that daily repeated consumption of pure sucralose or aspartame for 2 weeks had no effect on glucose metabolism among normoglycaemic adults. However, these results need to be tested in studies with longer durations. Novelty: • Daily consumption of pure aspartame or sucralose for 2 weeks had no effect on glucose metabolism. • Daily consumption of pure aspartame or sucralose for 2 weeks had no effect on insulin sensitivity among healthy adults.

    Matched MeSH terms: Area Under Curve
  16. Barakatun Nisak Mohd Yusof, Ruzita Abd. Talib, Norimah A. Karim, Nor Azmi Kamarudin, Fatimah Arshad
    MyJurnal
    White and whole meal breads have been classified as high glycemic index (GI) foods which in turn produce the greatest rise in blood glucose. One of the commercial bread products in Malaysia known as Brown breads (BB) has been recently marketed as a healthy choice for diabetics due to its low GI value. This study was conducted to examine the effect of BB when eaten with different fillings on blood glucose response among healthy individuals and to describe the influences of these fillings in reducing blood glucose response. Five test meals using BB (BB eaten with baked beans, BB eaten with vegetable, BB eaten with apple, BB eaten with roast chicken and BB eaten with seaweeds) had been prepared for this study. Postprandial blood glucose response was determined for each test meal and reference food (glucose) that contained 50 g carbohydrate respectively. A total of 21 healthy subjects were recruited by advertisement to participate. Only 20 subjects (15 males, 5 females, Mean + SD Age : 24.4 + 3.7 years; BMI 23.4 + 3.0 kgm-2) completed this study. After an overnight fast, subjects consumed BB eaten with fillings according to the assigned group given and three repeated tests of reference food (glucose). Fasting capillary blood glucose samples were taken at time 0 and at 15, 30, 45, 60, 90 and 120 min respectively after the meal began. The blood glucose response was obtained by calculating the incremental area under the curve (AUC). Blood glucose response after consuming reference food (251.8 + 12.1 mmol.min/L) was significantly higher than all the test meals (p < 0.05). Among the test meals, BB eaten with baked beans produced the highest rise in blood glucose (97.0 + 16.9 mmol.min/L) whereas BB eaten with seaweeds demonstrated the lowest response in blood glucose (33.3 + 6.5 mmol.min/L) and the difference was statistically significant (p < 0.05). The postprandial blood glucose response after ingestion of BB when eaten with vegetable was 73.3 + 19.1 mmol.min/L followed by BB eaten with apple (58.9 + 12.2 mmol.min/L) and BB eaten with roast chicken (56.5 + 10.1 mmol.min/L). Generally, BB when eaten with fillings produced a slow rise in blood glucose response than the reference food. Combining this BB with fillings had the effect of reducing the postprandial blood glucose further.
    Matched MeSH terms: Area Under Curve
  17. Liew MH, Ng S, Chew CC, Koo TW, Chee YL, Chee EL, et al.
    Invest New Drugs, 2017 04;35(2):145-157.
    PMID: 28070719 DOI: 10.1007/s10637-016-0415-y
    The sex-divergent pharmacokinetics and interaction of tyrosine kinase inhibitor sunitinib with paracetamol was evaluated in male and female mice. Mice (control groups) were administered 60 mg/kg PO sunitinib alone or with 200 mg/kg PO paracetamol (study groups). Sunitinib concentration in plasma, brain, kidney and liver were determined and non-compartmental pharmacokinetic analysis performed. Female control mice showed 36% higher plasma sunitinib AUC0→∞, 31% and 27% lower liver and kidney AUC0→∞ and 2.2-fold higher AUC0→∞ in brain (all p 
    Matched MeSH terms: Area Under Curve
  18. Lau CL, Chan ST, Selvaratanam M, Khoo HW, Lim AY, Modamio P, et al.
    Fundam Clin Pharmacol, 2015 Aug;29(4):404-16.
    PMID: 26011058 DOI: 10.1111/fcp.12126
    Tyrosine kinase inhibitor sunitinib (used in GIST, advanced RCC, and pancreatic neuroendocrine tumors) undergoes CYP3A4 metabolism and is an ABCB1B and ABCG2 efflux transporters substrate. We assessed the pharmacokinetic interaction with ibuprofen (an NSAID used by patients with cancer) in Balb/c male and female mice. Mice (study group) were coadministered (30 min apart) 30 mg/kg of ibuprofen and 60 mg/kg of sunitinib PO and compared with the control groups, which received sunitinib alone (60 mg/kg, PO). Sunitinib concentration in plasma, brain, kidney, and liver was measured by HPLC as scheduled and noncompartmental pharmacokinetic parameters estimated. In female control mice, sunitinib AUC0→∞ decreased in plasma (P < 0.05), was higher in liver and brain (P < 0.001), and lower in kidney (P < 0.001) vs. male control mice. After ibuprofen coadministration, female mice showed lower AUC0→∞ in plasma (P < 0.01), brain, liver, and kidney (all P < 0.001). However, in male mice, AUC0→∞ remained unchanged in plasma, increased in liver and kidney, and decreased in brain (all P < 0.001). The tissue-to-plasma AUC0→∞ ratio was similar between male and female control mice, but changed after ibuprofen coadministration: Male mice showed 1.6-fold higher liver-to-plasma ratio (P < 0.001) while remained unchanged in female mice and in kidney (male and female mice) but decreased 55% in brain (P < 0.05). The tissue-to-plasma partial AUC ratio, the drug tissue targeting index, and the tissue-plasma hysteresis-like plots also showed sex-based ibuprofen-sunitinib drug interaction differences. The results illustrate the relevance of this DDI on sunitinib pharmacokinetics and tissue uptake. These may be due to gender-based P450 and efflux/transporters differences.
    Matched MeSH terms: Area Under Curve
  19. Lim LL, Fu AWC, Lau ESH, Ozaki R, Cheung KKT, Ma RCW, et al.
    Nephrol Dial Transplant, 2019 Aug 01;34(8):1320-1328.
    PMID: 29939305 DOI: 10.1093/ndt/gfy154
    BACKGROUND: Early detection and risk factor control prevent chronic kidney disease (CKD) progression. Evaluation of peripheral autonomic dysfunction may detect incident cardiovascular-renal events in type 2 diabetes (T2D).

    METHODS: SUDOSCAN, a non-invasive tool, provides an age-adjusted electrochemical skin conductance (ESC) composite score incorporating hands/feet ESC measurements, with a score ≤53 indicating sudomotor dysfunction. A consecutive cohort of 2833 Chinese adults underwent structured diabetes assessment in 2012-13; 2028 participants without preexisting cardiovascular disease (CVD) and CKD were monitored for incident cardiovascular-renal events until 2015.

    RESULTS: In this prospective cohort {mean age 57.0 [standard deviation (SD) 10.0] years; median T2D duration 7.0 [interquartile range (IQR) 3.0-13.0] years; 56.1% men; 72.5% never-smokers; baseline ESC composite score 60.7 (SD 14.5)}, 163 (8.0%) and 25 (1.2%) participants developed incident CKD and CVD, respectively, after 2.3 years of follow-up. The adjusted hazard ratios (aHRs) per 1-unit decrease in the ESC composite score for incident CKD, CVD and all-cause death were 1.02 [95% confidence interval (CI) 1.01-1.04], 1.04 (1.00-1.07) and 1.04 (1.00-1.08), respectively. Compared with participants with an ESC composite score >53, those with a score ≤53 had an aHR of 1.56 (95% CI 1.09-2.23) for CKD and 3.11 (95% CI 1.27-7.62) for CVD, independent of common risk markers. When added to clinical variables (sex and duration of diabetes), the ESC composite score improved discrimination of all outcomes with appropriate reclassification of CKD risk.

    CONCLUSIONS: A low ESC composite score independently predicts incident cardiovascular-renal events and death in T2D, which may improve the screening strategy for early intervention.

    Matched MeSH terms: Area Under Curve
  20. Yahya N, Ebert MA, Bulsara M, House MJ, Kennedy A, Joseph DJ, et al.
    Med Phys, 2016 May;43(5):2040.
    PMID: 27147316 DOI: 10.1118/1.4944738
    Given the paucity of available data concerning radiotherapy-induced urinary toxicity, it is important to ensure derivation of the most robust models with superior predictive performance. This work explores multiple statistical-learning strategies for prediction of urinary symptoms following external beam radiotherapy of the prostate.
    Matched MeSH terms: Area Under Curve
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links