Displaying publications 21 - 40 of 55 in total

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  1. Therapeutic drug monitoring of gentamicin: a 6-year follow-up audit
    Ismail R, Haq AH, Azman M, Rahman AF
    J Clin Pharm Ther, 1997 Feb;22(1):21-5.
    PMID: 9292398
    In 1984 a therapeutic drug monitoring (TDM) service was established in Hospital Universiti Sains Malaysia (HUSM) and gentamicin concentrations were measured and used to design optimal regimens for the antibiotic. In this study we report on a 6-year follow-up audit since our first assessment of the service.
    Matched MeSH terms: Drug Monitoring*
  2. Population Pharmacokinetic Modeling of Cyclosporine Among Malaysian Renal Transplant Patients: An Evaluation of Methods to Handle Missing Doses in Conventional Drug-Monitoring Data
    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: Drug Monitoring*
  3. Kratom and Pain Tolerance: A Randomized, Placebo-Controlled, Double-Blind Study
    Vicknasingam B, Chooi WT, Rahim AA, Ramachandram D, Singh D, Ramanathan S, et al.
    Yale J Biol Med, 2020 06;93(2):229-238.
    PMID: 32607084
    Background: Kratom has a long history of traditional medicine use in Southeast Asia. Consumption of kratom products has also been reported in the US and other regions of the world. Pain relief is among many self-reported kratom effects but have not been evaluated in controlled human subject research. Methods: Kratom effects on pain tolerance were assessed in a randomized, placebo-controlled, double-blind study. During a 1-day inpatient stay, participants received a randomized sequence of kratom and placebo decoctions matched for taste and appearance. Pain tolerance was measured objectively in a cold pressor task (CPT) as time (seconds) between the pain onset and the hand withdrawal from the ice bath. Health status, vital signs, objective, and subjective indicators of withdrawal symptoms, self-reported data on lifetime kratom use patterns, and assessments of blinding procedures were also evaluated. Results: Twenty-six males with the mean (SD) age 24.3 (3.4) years were enrolled. They reported the mean (SD) 6.1 (3.2) years of daily kratom consumption. Pain tolerance increased significantly 1 hour after kratom ingestion from the mean (SD) 11.2 (6.7) seconds immediately before to 24.9 (39.4) seconds 1 hour after kratom consumption (F(2,53.7)=4.33, p=0.02). Pain tolerance was unchanged after consuming placebo drinks: 15.0 (19.0) seconds immediately before and 12.0 (8.1) seconds 1 hour after consumption of placebo (F(2,52.8)=0.93, p=0.40). No discomfort or signs of withdrawal were reported or observed during 10-20 hours of kratom discontinuation. Conclusions: Kratom decoction demonstrated a substantial and statistically significant increase in pain tolerance. Further rigorous research on kratom pain-relieving properties and a safety profile is needed.
    Matched MeSH terms: Drug Monitoring/methods
  4. Fulltext Short Communication: Impact of Viral Load Use on Treatment Switch in Perinatally HIV-Infected Children in Asia
    Jamal Mohamed T, Teeraananchai S, Kerr S, Phongsamart W, Nik Yusoff NK, Hansudewechakul R, et al.
    AIDS Res Hum Retroviruses, 2017 03;33(3):230-233.
    PMID: 27758114 DOI: 10.1089/AID.2016.0039
    We sought to assess the impact of routine HIV viral load (VL) monitoring on the incidence of switching from a first- to a second-line antiretroviral therapy (ART) regimen, and to describe factors associated with switch. Data from a regional cohort of 16 clinical programs in six Asian countries were analyzed. Second-line switch was defined as a change from a non-nucleoside reverse transcriptase inhibitor (NNRTI) to a protease inhibitor (PI) or vice versa, and ≥1 of the following: (1) reported treatment failure by local criteria, (2) switch of ≥1 additional drug, or (3) a preceding HIV VL ≥1,000 copies/ml. Routine VL was having ≥1 test after ≥24 weeks of ART and ≥1 time/year thereafter. Factors associated with time to switch were evaluated with death and loss to follow-up as competing risks. A total of 2,398 children were included in this analysis. At ART initiation, the median (interquartile range) age was 6.0 (3.3-8.9) years, more than half had WHO stage 3 or 4, the median CD4 was 189 (47-456) cells/mm3, 93% were on NNRTI-based first-line ART, and 34% had routine VL monitoring. Treatment switch occurred in 17.6% of patients, at a median of 35 (22-49) months. After adjusting for country, sex, first ART regimen, and CD4% at ART initiation, children with routine VL monitoring were 1.46 (95% confidence interval 1.11-1.93) times more likely to be switched (p = .007). Scale-up of VL testing will lead to earlier identification of treatment failure, and it can help guide earlier switches to prevent resistance.
    Matched MeSH terms: Drug Monitoring/methods*
  5. Estimating drug-free period using a graphical method: an alternative way to monitor extended-interval dosing of gentamicin therapy
    Ab Rahman AF, Md Sahak N, Ali AM
    Int J Pharm Pract, 2017 Feb;25(1):75-80.
    PMID: 28097717 DOI: 10.1111/ijpp.12336
    OBJECTIVES: Published nomograms to monitor extended-interval dosing (EID) gentamicin therapy were based on a fixed dose of 5 or 7 mg/kg. However, the average dose used for EID gentamicin regimen in our setting was about 3 mg/kg per day. We developed a new method of monitoring based on the duration of drug-free period (DFP) in a 24-h dosing interval.

    METHODS: Hospitalised adult patients on EID gentamicin were selected. We considered a DFP of between 2 and 8 h as appropriate. Data from two blood samples (2 and 6 h postdose) from each patient were used to estimate the duration of DFP (i.e. DFP method 1). DFP was also calculated for the same patient using an empirically estimated elimination rate constant (Ke ) and the same 6 h postdose concentration value (DFP method 2). Correlation between the two methods was made. An alternative graphical method to estimate DFP was attempted.

    KEY FINDINGS: Correlation between Ke and age was favourable (r = -0.453; P = 0.001). Ke derived from this empirical relationship was used to estimate DFP method 2. DFP method 1 correlated well with DFP method 2 (r = 0.742; P 

    Matched MeSH terms: Drug Monitoring/methods*
  6. Monitoring of tobramycin in human plasma via mixed matrix membrane extraction prior to capillary electrophoresis with contactless conductivity detection
    Mukhtar NH, Mamat NA, See HH
    J Pharm Biomed Anal, 2018 Sep 05;158:184-188.
    PMID: 29883881 DOI: 10.1016/j.jpba.2018.05.044
    A sample pre-treatment method based on a dynamic mixed matrix membrane tip extraction followed by capillary electrophoresis with contactless conductivity detection (CE-C4D) was evaluated for the determination of tobramycin in human plasma. The extraction tip device consisted of a cellulose triacetate membrane tip wall immobilised with 15% (w/w) of hydrophilic lipophilic balance (HLB) nanoparticles as adsorbent. The extraction was performed dynamically by withdrawing/dispensing the plasma sample through the tip device followed by desorption into 20 μL of acidified aqueous solution at pH 3 prior to the CE-C4D analysis. Under the optimum conditions, the detection limit of the method for tobramycin was 10 ng/mL, with intraday and interday repeatability RSDs of 3.5% and 4.5%, respectively. Relative recoveries in spiked human plasma were 99.6%-99.9%. The developed approach was successfully demonstrated for the quantification of tobramycin in human plasma samples.
    Matched MeSH terms: Drug Monitoring/methods*
  7. The potential for evaluating the effects of intensified antithrombotic therapy using retinal optical coherence tomography angiography
    Aik Kah T
    Med Hypotheses, 2018 Jun;115:54-57.
    PMID: 29685198 DOI: 10.1016/j.mehy.2018.03.022
    Oral anticoagulants are widely used in the treatment and prevention of both venous and arterial thromboembolism. They are classified into vitamin K anticoagulants (VKAs) and non-vitamin K antagonist oral anticoagulants (NOACs). The main advantage of NOACs over VKAs is the absence of the need for continuous monitoring. However, there are concerns about their effectiveness and safety in certain clinical situations. In this manuscript, I discussed the possibility of using optical coherence tomography angiography [OCTA] in the monitoring of the activity of NOACs. The rapid development of OCTA technology is very promising. Further research and development will extend its use beyond the realm of ophthalmology.
    Matched MeSH terms: Drug Monitoring/methods
  8. Pharmacometabonomics Technique to Identify Warfarin Response Using Nuclear Magnetic Resonance Spectroscopy
    Bawadikji AA, Teh CH, Kader MABSA, Sulaiman SAS, Ibrahim B
    Curr Pharm Biotechnol, 2017;18(9):740-747.
    PMID: 29110602 DOI: 10.2174/1389201018666171103141828
    BACKGROUND: Warfarin, an anticoagulant medication, is prescribed regularly despite of its bleeding tendency for the prevention and/or treatment of various thromboembolic conditions, such as deep vein thrombosis, and complications associated with atrial fibrillation, and myocardial infarction, but because of its narrow therapeutic window, it has a lot of interactions with drugs and diet.

    METHODS: Warfarin relies on regular monitoring of International Normalized Ratio which is a standardized test to measure prothrombin time and appropriate dose adjustment. Pharmacometabonomics is a novel scientific field which deals with identification and quantification of the metabolites present in the metabolome using spectroscopic techniques such as Nuclear Magnetic Resonance (NMR). Pharmacometabonomics helps to indicate perturbation in the levels of metabolites in the cells and tissues due to drug or ingestion of any substance. NMR is one of the most widely-used spectroscopic techniques in metabolomics because of its reproducibility and speed.

    RESULTS: There are many factors that influence the metabolism of warfarin, making changes in drug dosage common, and clinical factors like drug-drug interactions, dietary interactions and age explain for the most part the variability in warfarin dosing. Some studies have showed that pharmacogenetic testing for warfarin dosing does not improve health outcomes, and around 26% of the variation in warfarin dose requirements remains unexplained yet.

    CONCLUSION: Many recent pharmacometabonomics studies have been conducted to identify novel biomarkers of drug therapies such as paracetamol, aspirin and simvastatin. Thus, a technique such as NMR based pharmacometabonomics to find novel biomarkers in plasma and urine might be useful to predict warfarin outcome.

    Matched MeSH terms: Drug Monitoring/methods*
  9. Practices associated with serum antiepileptic drug level monitoring at a pediatric neurology clinic: a Malaysian experience
    Salih MR, Bahari MB, Hassali MA, Shafie AA, Al-Lela OQ, Abd AY, et al.
    J Pharm Pract, 2013 Jun;26(3):192-7.
    PMID: 22797836 DOI: 10.1177/0897190012451926
    OBJECTIVES: To assess the practices associated with the application of therapeutic drug monitoring (TDM) for antiepileptic drugs (AEDs) in the management of children with structural-metabolic epilepsy.
    METHODS: It was a retrospective chart review and included children aged ≥2 years old with structural-metabolic epilepsy, treated with AEDs, and received TDM. The data were extracted from the medical records.
    RESULTS: Thirty-two patients were identified with 50 TDM assays. In two thirds of the assays, "check level" and "recheck level" were the reasons behind the requesting of serum level monitoring of AEDs. Knowledge of serum AED levels led to alterations in the management in 60% of the assays. Thirty-two (76%) pediatrician's actions were consistent with the recommendation of TDM pharmacist. Forty-nine (98%) levels were appropriately indicated. In relation to the appropriateness of sampling time, 9 (18%) levels were not assessed due to missing data. Twenty-seven (54%) levels were appropriately sampled.
    CONCLUSIONS: More studies should be designed to improve the component of the current TDM request form, especially in the reason section. By the same token, the number of pointless assays and the costs to the health care system can be reduced both by enhancing and improving the educational standards of the requesting neurologists.
    KEYWORDS: Malaysia; epilepsy; neurology; pediatrics; therapeutic drug monitoring
    Study site: Paediatric Neurology Clinic, Hospital Pulau Pinang, Malaysia
    Matched MeSH terms: Drug Monitoring/methods*
  10. How well does self-reported adherence fare compared to therapeutic drug monitoring in HAART?
    Bulgiba A, Mohammed UY, Chik Z, Lee C, Peramalah D
    Prev Med, 2013;57 Suppl:S34-6.
    PMID: 23313585 DOI: 10.1016/j.ypmed.2013.01.002
    The aim of the study was to determine how well self-reported adherence fares compared to therapeutic drug monitoring in monitoring HAART adherence.
    Matched MeSH terms: Drug Monitoring/methods*
  11. Chloramphenicol in children: dose, plasma levels and clinical effects
    Ismail R, Teh LK, Choo EK
    Ann Trop Paediatr, 1998 Jun;18(2):123-8.
    PMID: 9924573
    Despite concerns about adverse effects, chloramphenicol (CMC) continues to be used in certain situations and, due to its low therapeutic index and variable pharmacokinetics, therapeutic drug monitoring (TDM) is often recommended. At our centre, CMC finds applications in typhoid and meningitis and TDM is routinely performed. Elsewhere in Malaysia, however, CMC is used without TDM. We therefore decided to evaluate our TDM for CMC in relation to its roles in CMC therapy in children, who constitute most of our patients. Our objective was also to develop strategies to improve our TDM for CMC use. Data were collected from 168 children given CMC for various indications and monitored by the TDM service. Plasma CMC was determined by HPLC and used to adjust doses to maintain concentrations within a range of 10-25 micrograms/ml. Outcomes measured included daily temperatures and haematological indices. Daily doses and plasma CMC varied greatly. Doses averaged 40.5 mg/kg for neonates and 75.5 for older children. Average peak concentrations were therapeutic in 60% and trough in 42%. Average duration of fever was 6.3 days and it was unaffected by plasma CMC. Typhoid was eradicated in 97% but nine children with other diagnoses died. Side-effects were confined to mild reversible haematological abnormalities which developed in 11% of children at plasma concentrations which tended to be high. We conclude that CMC remains useful in children with typhoid. Its use for other indications, however, should be reviewed. Routine TDM for CMC is probably not warranted, at least until a clearer role is defined by well designed prospective studies.
    Matched MeSH terms: Drug Monitoring/methods
  12. Fulltext Improving the appropriateness of therapeutic drug monitoring sampling in Hospital Sultanah Nur Zahirah, Kuala Terengganu
    Lukman Nul Hakim Md Khairi, Farah Syakirah Ahmad, Aimi Shazana Muhammad Anuar, Nurul Ain Wan Omar, Nurul Najmi Muhammad, Nurulhayati Abd. Jamal, et al.
    Q Bulletin, 2020;1(29):28-35.
    MyJurnal
    Therapeutic drug monitoring (TDM) is a valuable clinical tool in optimisation of drug regimens. However, improper utilisation of TDM may lead to significant resource wastage and expose patients to avoidable trauma, toxicity, therapeutic failure and prolonged hospitalisation. This study aimed to reduce the percentage of inappropriate TDM sampling to our proposed standard of less than 20% within a four-month intervention period. A cross-sectional study was undertaken from January to December 2015 at the inpatient setting of Hospital Sultanah Nur Zahirah. Gentamicin and Vancomycin analytes were studied because these analytes accounted for 69.2% of total samples received in 2014. TDM Monitoring Form was used to collect sampling and dosage information to assess sampling appropriateness. A closed-ended self-administered questionnaire was distributed to a group of medical doctors to assess their knowledge on appropriate Gentamicin and Vancomycin TDM sampling method pre- and post-intervention. Prior to the intervention phase in October to December 2014, 79.4% of TDM were inappropriately sampled. The main contributing factors were inadequate knowledge among medical doctors, lack of sampling reminders for new TDM requests, and misunderstanding on sampling information for repeated TDM requests. 60-minute face-to-face educational sessions on TDM sampling method were conducted specifically for staff at the General Medical and Paediatric Departments, and two continuing medical education (CME) slots were held at the hospital level. Guidelines on TDM sampling was initiated and laminated copies were distributed to all wards. Implementation of TDM Alert System which consisted of digital reminders and physical stickers was also introduced. The interventions were able to reduce the inappropriate sampling percentage from 79.4% to 41.8% post-intervention, and to 19.1% in the recent monitoring phase of January until June 2019. Continuous close monitoring and sustainable implementation of the measures are vital as TDM sampling appropriateness may affect clinical interpretation of the results.
    Matched MeSH terms: Drug Monitoring
  13. Fulltext An evaluation on pharmacokinetics parameters of phenytoin in adult epileptic patients: a single centre study from Malaysia
    Tan, Kenny, Luen, Leong Wei, Ong, Yi Ping, Khai, H’ng Kee, Tan, Li May, Siti Nur Fatihah Abd Rahman, et al.
    Malaysian Journal of Pharmaceutical Science, 2020;18(1):77-83.
    MyJurnal
    Phenytoin follows Michaelis-Menten, a non-linear pharmacokinetics that occurs when drug molecules saturates the enzymes ability to metabolise the drug. When this occurs, steady state phenytoin serum concentration increases in a disproportionate manner after a dosage increase. General population data are usually used for the phenytoin dose calculation. However, many studies show that population pharmacokinetic parameters of phenytoin have high variations. Thus, use of specific local pharmacokinetic parameters for each population group in estimating individualised phenytoin dose can reduce phenytoin toxicity cases. This prospective, observational study was conducted to estimate a local Vmax and Km of phenytoin for adult epileptic patients in neurological ward and clinic at Hospital Pulau Pinang, Malaysia. All therapeutic drug monitoring of oral capsule phenytoin were studied in a three-month data collection period. Out of the 17 subjects in our study, there are 13 male subjects (76.47%) and 4 female subjects (23.53%). A total 11 Malay subjects (64.71%), 4 Chinese subjects (23.53%) and 2 Indian subjects (11.76%) were included. Median Vmax and Km were found to be 8.25 mg/kg/day and 3.80 mg/l. Male subjects have a higher Vmax (8.30 mg/kg/day) but a lower Km (3.3 mg/l). Chinese population has the highest Vmax (8.80 mg/kg/day). For Km, Indian population is the highest, with a value of 5.5 mg/l. From our study, gender does not correlate with Vmax and Km of phenytoin (p-value > 0.05). Ethnicity was also found to have no association with Vmax and Km (p-value > 0.05). Local Vmax (8.25 mg/kg/day) is higher and Km (3.8 mg/l) is lower when compared with standard Vmax (7 mg/kg/day) and Km (4 mg/l) obtained from Caucasian population.
    Matched MeSH terms: Drug Monitoring
  14. Changes in serum perampanel concentration profile after discontinuation of carbamazepine
    Murugesu S, Okayama K, Yamamoto Y, Terada K, Takahashi Y
    Epileptic Disord, 2020 Aug 01;22(4):455-461.
    PMID: 32782230 DOI: 10.1684/epd.2020.1182
    To evaluate changes in the pharmacokinetics of perampanel after discontinuation of carbamazepine. We enrolled 13 patients receiving perampanel who discontinued carbamazepine therapy between June 2016 and December 2018. Data on serum concentrations were obtained from the therapeutic drug monitoring database of the National Epilepsy Center (Shizuoka, Japan). To compare the pharmacokinetics of perampanel before and after discontinuation of carbamazepine, we determined the concentration/dose (CD) ratio of perampanel (serum level [ng/mL] divided by the dose [mg/kg]). The follow-up period was set to eight weeks following the discontinuation of carbamazepine therapy. The mean baseline CD ratio of perampanel was 1,247 ng/mL/mg/kg which increased markedly over time after discontinuation of carbamazepine, with a mean CD ratio at Weeks 1-2, Weeks 3-4, and Weeks 5-8 of 2,683, 3,914, and 4,220, respectively. At eight weeks, the mean CD ratio of perampanel had increased by 276%. Eleven patients developed adverse events, including dizziness, somnolence, irritability, and ataxia. Five of these 11 patients required perampanel dose reduction within eight weeks after discontinuation of carbamazepine. Two patients achieved seizure-free status at Weeks 5-8. The serum perampanel concentration began to increase from one week after discontinuation of carbamazepine, and continued to rise for eight weeks. Based on these findings, we recommend frequent monitoring of serum perampanel concentration for at least eight weeks after stopping carbamazepine therapy. Monitoring is required as a guide for dose adjustment in order to achieve a safe and effective therapeutic dose of perampanel.
    Matched MeSH terms: Drug Monitoring
  15. Fulltext Management of Outpatient Warfarin Therapy amid COVID-19 Pandemic: A Practical Guide
    Kow CS, Sunter W, Bain A, Zaidi STR, Hasan SS
    Am J Cardiovasc Drugs, 2020 Aug;20(4):301-309.
    PMID: 32458370 DOI: 10.1007/s40256-020-00415-z
    Many healthcare resources have been and continue to be allocated to the management of patients with COVID-19. Therefore, the ongoing care of patients receiving oral anticoagulation with warfarin is likely to be compromised amid this unprecedented crisis. This article discusses a stepwise algorithm for the management of outpatient warfarin therapy. Alternative management strategies are presented and discussed, including alternative pharmacological therapy options and self-monitoring. Our algorithm aims to help clinicians safely optimize the treatment of patients requiring anticoagulation therapy in the context of the global response to the current pandemic.
    Matched MeSH terms: Drug Monitoring
  16. Fulltext CYP2C9 polymorphism: prevalence in healthy and warfarin-treated Malay and Chinese in Malaysia
    Ngow HA, Wan Khairina WM, Teh LK, Lee WL, Harun R, Ismail R, et al.
    Singapore Med J, 2009 May;50(5):490-3.
    PMID: 19495518
    Genetic polymorphisms of CYP2C9 among different populations in different geographical regions could be different. CYP2C9 has been reported to be the enzyme responsible for the metabolism of many drugs, including warfarin and other drugs with a narrow therapeutic index. Realising the importance of inter-individual differences in the genetic profile in determining the outcome of a drug therapy, this study was conducted to explore the types and frequencies of CYP2C9 alleles in healthy and warfarin-treated Malays and Chinese, the two major ethnic groups in Malaysia. We aimed to evaluate the prevalence of the types and frequencies of common CYP2C9 alleles (*1, *2, *3 and *4) among the healthy unrelated individuals and diseased patients prescribed with warfarin.
    Matched MeSH terms: Drug Monitoring
  17. Comparing effectiveness of two anticoagulation management models in a Malaysian tertiary hospital
    Thanimalai S, Shafie AA, Hassali MA, Sinnadurai J
    Int J Clin Pharm, 2013 Oct;35(5):736-43.
    PMID: 23715759 DOI: 10.1007/s11096-013-9796-6
    BACKGROUNDS: Limited evidence is available regarding pharmacist managed anticoagulation clinic in the Southeast Asian region where there is marked difference in terms of care model, genetic composition and patient demographics.

    OBJECTIVES: This study aimed at comparing the anticoagulation clinic managed by the pharmacist with physician advisory and the usual medical care provided in Kuala Lumpur Hospital (KLH) in terms of anticoagulation control and adverse outcomes.

    SETTING: A 2,302 bedded government tertiary referral hospital in Malaysia.

    METHODS: A 6-month retrospective cohort study of the effectiveness of two models of anticoagulation care, the pharmacist managed anticoagulation clinic which is known as warfarin medication therapy adherence clinic (WMTAC) and usual medical clinic (UMC) in KLH was conducted, where a random number generator was used to recruit patients. The UMC patients received standard medical care where they are managed by rotational medical officers in the physicians' clinic. As for the WMTAC with physician advisory, the pharmacist will counsel and review the patients internationalised normalization ratio at each clinic visit and also adjust the patients' warfarin dose accordingly. Patients are referred to physicians if immediate attention is required.

    MAIN OUTCOME MEASURE: The main therapeutic outcome is time in therapeutic range (TTR) both actual and expanded TTR and thromboembolic and bleeding complications.

    RESULTS: Each of the WMTAC and usual medical care recruited 92 patients, which totals to 184 patients. The patient demographics in terms of age, race and indication of treatment were comparable. At the end of the 6 months follow-up, patients in the WMTAC group had significantly higher actual-TTR (65.1 vs. 48.3 %; p < 0.05) compared to those in usual medical care group. Rates of admission were 6.5 versus 28.2 events per 100 person-years for the WMTAC and UMC groups, respectively. Though the bleeding incidences were not significantly different, it was reduced.

    CONCLUSIONS: These findings will impact local warfarin patient management services and policies because there was no available evidence supporting the role of pharmacists in the management of warfarin patients prior to this study.
    Matched MeSH terms: Drug Monitoring*
  18. Pharmacometabolomics analysis of plasma to phenotype clopidogrel high on treatment platelets reactivity in coronary artery disease patients
    Amin AM, Sheau Chin L, Teh CH, Mostafa H, Mohamed Noor DA, Abdul Kader MASK, et al.
    Eur J Pharm Sci, 2018 May 30;117:351-361.
    PMID: 29526765 DOI: 10.1016/j.ejps.2018.03.011
    Dual antiplatelet therapy (DAPT) of clopidogrel and aspirin is crucial for coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI). However, some patients may endure clopidogrel high on treatment platelets reactivity (HTPR) which may cause thromboembolic events. Clopidogrel HTPR is multifactorial with some genetic and non-genetic factors contributing to it. We aimed to use nuclear magnetic resonance (1H NMR) pharmacometabolomics analysis of plasma to investigate this multifactorial and identify metabolic phenotypes and pathways associated with clopidogrel HTPR. Blood samples were collected from 71 CAD patients planned for interventional angiographic procedure (IAP) before the administration of clopidogrel 600 mg loading dose (LD) and 6 h after the LD. Platelets function testing was done 6 h post-LD using VerifyNow® P2Y12 assay. Pre-dose and post-dose plasma samples were analysed using 1H NMR. Multivariate statistical analysis was used to indicate the discriminating metabolites. Two metabotypes, each with 34 metabolites (pre-dose and post-dose) were associated with clopidogrel HTPR. Pathway analysis of these metabotypes revealed that aminoacyl-tRNA biosynthesis, nitrogen metabolism and glycine-serine-threonine metabolism are the most perturbed metabolic pathways associated with clopidogrel HTPR. Furthermore, the identified biomarkers indicated that clopidogrel HTPR is multifactorial where the metabolic phenotypes of insulin resistance, type two diabetes mellitus, obesity, gut-microbiota and heart failure are associated with it. Pharmacometabolomics analysis of plasma revealed new insights on the implicated metabolic pathways and the predisposing factors of clopidogrel HTPR.
    Matched MeSH terms: Drug Monitoring/methods
  19. Fulltext A metabolomic analysis of thiol response for standard and modified N-acetyl cysteine treatment regimens in patients with acetaminophen overdose
    Dear JW, Ng ML, Bateman DN, Leroy Sivappiragasam P, Choi H, Khoo BBJ, et al.
    Clin Transl Sci, 2021 Jul;14(4):1476-1489.
    PMID: 33742775 DOI: 10.1111/cts.13009
    N-acetylcysteine (NAC) is an antidote to prevent acetaminophen (paracetamol-APAP)-induced acute liver injury (ALI). The 3-bag licensed 20.25 h standard regimen, and a 12 h modified regimen, are used to treat APAP overdose. This study evaluated the redox thiol response and APAP metabolites, in patients with a single APAP overdose treated with either the 20.25 h standard or 12 h modified regimen. We used liquid chromatography tandem mass spectrometry to quantify clinically important oxidative stress biomarkers and APAP metabolites in plasma samples from 45 patients who participated in a randomized controlled trial (SNAP trial). We investigated the time course response of plasma metabolites at predose, 12 h, and 20.25 h post-start of NAC infusion. The results showed that the 12 h modified regimen resulted in a significant elevation of plasma NAC and cysteine concentrations at 12 h post-infusion. We found no significant alteration in the metabolism of APAP, mitochondrial, amino acids, and other thiol biomarkers with the two regimens. We examined APAP and purine metabolism in overdose patients who developed ALI. We showed the major APAP-metabolites and xanthine were significantly higher in patients with ALI. These biomarkers correlated well with alanine aminotransferase activity at admission. Receiver operating characteristic analysis showed that at admission, plasma APAP-metabolites and xanthine concentrations were predictive for ALI. In conclusion, a significantly higher redox thiol response with the modified NAC regimen at 12 h postdose suggests this regimen may produce greater antioxidant efficacy. At baseline, plasma APAP and purine metabolites may be useful biomarkers for early prediction of APAP-induced ALI.
    Matched MeSH terms: Drug Monitoring/methods
  20. Fulltext Efficacy of azithromycin in the treatment of bronchiectasis
    Lourdesamy Anthony AI, Muthukumaru U
    Respirology, 2014 Nov;19(8):1178-82.
    PMID: 25183304 DOI: 10.1111/resp.12375
    We evaluated the efficacy of a 12-week oral treatment with azithromycin in adult patients with bronchiectasis. The objectives were to demonstrate that this treatment reduces sputum volume, improves quality of life and to assess the lengths of effects after cessation of therapy.
    Matched MeSH terms: Drug Monitoring
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