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  1. Fulltext Extended-interval gentamicin dosing in achieving therapeutic concentrations in malaysian neonates
    Low YS, Tan SL, Wan AS
    J Pediatr Pharmacol Ther, 2015 Mar-Apr;20(2):119-27.
    PMID: 25964729 DOI: 10.5863/1551-6776-20.2.119
    OBJECTIVE: To evaluate the usefulness of extended-interval gentamicin dosing practiced in neonatal intensive care unit (NICU) and special care nursery (SCN) of a Malaysian hospital.
    METHODS: Cross-sectional observational study with pharmacokinetic analysis of all patients aged ≤28 days who received gentamicin treatment in NICU/SCN. Subjects received dosing according to a regimen modified from an Australian-based pediatric guideline. During a study period of 3 months, subjects were evaluated for gestational age, body weight, serum creatinine concentration, gentamicin dose/interval, serum peak and trough concentrations, and pharmacokinetic parameters. Descriptive percentages were used to determine the overall dosing accuracy, while analysis of variance (ANOVA) was conducted to compare the accuracy rates among different gestational ages. Pharmacokinetic profile among different gestational age and body weight groups were compared by using ANOVA.
    RESULTS: Of the 113 subjects included, 82.3% (n = 93) achieved therapeutic concentrations at the first drug-monitoring assessment. There was no significant difference found between the percentage of term neonates who achieved therapeutic concentrations and the premature group (87.1% vs. 74.4%), p = 0.085. A total of 112 subjects (99.1%) achieved desired therapeutic trough concentration of <2 mg/L. Mean gentamicin peak concentration was 8.52 mg/L (95% confidence interval [Cl], 8.13-8.90 mg/L) and trough concentration was 0.54 mg/L (95% CI, 0.48-0.60 mg/L). Mean volume of distribution, half-life, and elimination rate were 0.65 L/kg (95% CI, 0.62-0.68 L/kg), 6.96 hours (95% CI, 6.52-7.40 hours), and 0.11 hour(-1) (95% CI, 0.10-0.11 hour(-1)), respectively.
    CONCLUSION: The larger percentage of subjects attaining therapeutic range with extended-interval gentamicin dosing suggests that this regimen is appropriate and can be safely used among Malaysian neonates.
    KEYWORDS: aminoglycosides; extended-interval; gentamicin; neonate; pharmacokinetics
  2. Fulltext Modification of Initial Highly Active Antiretroviral Therapy (HAART) Regimen in Paediatric HIV Patients
    Low YS, Islahudin F, Razali KAM, Adnan S
    Open AIDS J, 2018;12:11-19.
    PMID: 29576815 DOI: 10.2174/1874613601812010011
    BACKGROUND: Treatment options among Human Immunodeficiency Virus (HIV)-infected children are limited as only a few Highly Active Antiretroviral Therapy (HAART) are approved worldwide for paediatric use. Among children, frequent changes in HAART regimen can rapidly exhaust treatment options, and information addressing this issue is scarce.

    OBJECTIVE: The aim of the study was to determine factors associated with the modification of initial HAART regimen modification among HIV-infected children.

    METHOD: A retrospective study was performed among HIV-infected children aged 18 and below, that received HAART for at least six months in a tertiary hospital in Malaysia. Factors associated with modification of initial HAART regimen were investigated.

    RESULTS: Out of 99 patients, 71.1% (n=71) required initial HAART regime modification. The most common reason for HAART modification was treatment failure (n=39, 54.9%). Other reasons included drug toxicity (n=14, 19.7%), change to fixed-dose products (n=11, 15.5%), product discontinuation (n=4, 5.6%) and intolerable taste (n=3, 4.2%). The overall mean time retention on initial HAART before regimen modification was 3.32 year ± 2.24 years (95% CI, 2.79-3.85). Patient's adherence was the only factor associated with initial regimen modification in this study. Participants with poor adherence showed a five-fold risk of having their initial HAART regimen modified compared to those with good adherence (adjusted OR [95% CI], 5.250 [1.614 - 17.076], p = 0.006).

    CONCLUSION: Poor adherence was significantly associated with initial regimen modification, intervention to improve patient's adherence is necessary to prevent multiple regimen modification among HIV-infected children.

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