Volumetric absorptive microsampling (VAMS) is the newest and most promising sample-collection technique for quantitatively analyzing drugs, especially for routine therapeutic drug monitoring (TDM) and pharmacokinetic studies. This technique uses an absorbent white tip to absorb a fixed volume of a sample (10–50 µL) within a few seconds (2–4 s), is more flexible, practical, and more straightforward to be applied in the field, and is probably more cost-effective than conventional venous sampling (CVS). After optimization and validation of an analytical method of a drug taken by VAMS, a clinical validation study is needed to show that the results by VAMS can substitute what is gained from CVS and to justify implementation in routine practice. This narrative review aimed to assess and present studies about optimization and analytical validation of assays for drugs taken by VAMS, considering their physicochemical drug properties, extraction conditions, validation results, and studies on clinical validation of VAMS compared to CVS. The review revealed that the bio-analysis of many drugs taken with the VAMS technique was optimized and validated. However, only a few clinical validation studies have been performed so far. All drugs that underwent a clinical validation study demonstrated good agreement between the two techniques (VAMS and CVS), but only by Bland–Altman analysis. Only for tacrolimus and mycophenolic acid were three measurements of agreement evaluated. Therefore, VAMS can be considered an alternative to CVS in routine practice, especially for tacrolimus and mycophenolic acid. Still, more extensive clinical validation studies need to be performed for other drugs.
Multidrug-resistant tuberculosis (MDR-TB) is an infectious disease caused by Mycobacterium tuberculosis which is resistant to at least isoniazid and rifampicin. This disease is a worldwide threat and complicates the control of tuberculosis (TB). Long treatment duration, a combination of several drugs, and the adverse effects of these drugs are the factors that play a role in the poor outcomes of MDR-TB patients. There have been many studies with repurposed drugs to improve MDR-TB outcomes, including clofazimine. Clofazimine recently moved from group 5 to group B of drugs that are used to treat MDR-TB. This drug belongs to the riminophenazine class, which has lipophilic characteristics and was previously discovered to treat TB and approved for leprosy. This review discusses the role of clofazimine as a treatment component in patients with MDR-TB, and the drug’s properties. In addition, we discuss the efficacy, safety, and tolerability of clofazimine for treating MDR-TB. This study concludes that the clofazimine-containing regimen has better efficacy compared with the standard one and is also well-tolerated. Clofazimine has the potential to shorten the duration of MDR-TB treatment.
Background: Tuberculous meningitis (TBM) is the most common central nervous system infection of Mycobacterium tuberculosis (M.tb). The infection will cause focal neurological deficits and can be fatal, so that it will increase the morbidity and mortality rates. Adequate treatment is needed so that the drug can reach the center of infection. Not all anti-tuberculosis (TB) drugs can effectively cross the blood–brain and blood-cerebrospinal fluid barriers. The use of higher doses is expected to be able to work on the center of infection effectively. However, the use of higher doses will also increase the risk of drug-induced liver injury, which requires temporary discontinuation of the suspected drug. Methods: This scientific work aims to determine the penetration rate of first-line anti-TB drugs that are often used in patients infected with M.tb, especially TBM. Journal searches were performed on PubMed/PMC and BioMed Central/BMC search engines with the appropriate keywords. Critical appraisal analysis was carried out in selected journals. CSF sampling can be done to establish the diagnosis of TBM. CSF characteristics in TBM include lymphocyte pleocytosis, increased protein levels, and decreased glucose levels. Results: The results of CSF analysis depend on the volume of CSF used, the delivery of the sample, and the technical expertise of the clinician. If clinically, a patient is suspected of having TBM even though the results of CSF analysis show negative results for M.tb bacteria, a drug regimen can be given immediately to prevent worsening of the patient’s condition. Bacterial cultures may be performed as treatment progresses. Based on the penetration rate of anti-TB drugs in the CSF, isoniazid (INH), pyrazinamide, and fluoroquinolones, especially levofloxacin, are drugs with fairly good CSF penetration. Conclusion: The use of INH is beneficial because it has high bactericidal activity. Gatifloxacin and ciprofloxacin, which are included in the fluoroquinolone class of drugs, are safe to use even though their CSF penetration is not as good as levofloxacin.
The effect of acetylator status on the exposure to isoniazid in plasma and CSF in tuberculous meningitis (TBM) patients remains largely unexplored. Here, we describe isoniazid exposures and acetylator status of 48 subjects in the ReDEFINe study (NCT02169882). Fifty percentwere fast (half-life 130 min) acetylators. Slow acetylators had higher AUC0-24, Cmax and CSF concentrations than fast acetylators (GM AUC0-24 25.5 vs 10.6 mg/L*h, p < 0.001); plasma Cmax 5.5 vs 3.6 mg/L, p = 0.023; CSF concentration 1.9 vs 1.1 mg/L, p = 0.008). Higher isoniazid doses may benefit fast acetylators in TBM.
1 September 2019 in International Journal of Integrated Health Sciences
Objective: Adherence to medication is crucial for hypertension patients in order to control and prevent complications. This study aimed to describe the adherence to antihypertensive drugs among patients with hypertension in Bandung District, West Java, Indonesia. Methods: This was a cross-sectional observational study on patients with hypertension in the work area of Cileunyi Public Health Center (PHC), Bandung District, West Java, Indonesia. The inclusion criteria used were patients with hypertension who were prescribed an antihypertensive drug by a physician, above 18 years old, and had been using an antihypertensive medication for at least two months before the study. Data were obtained through interviews during the month of July to August 2018 using a modified MMAS-8 questionnaireof the Morisky Medication Adherence Scale (MMAS-8), which includes Likert-type scale questions. Data collected were then analyzed using the Rasch Model, and the mean logit person was used as a cut off between adherence and non-adherence categories. Results: A total of 75 patients with hypertension were recruited. The prevalence of adherence to medication was 59%. Most patients who adhered to the medication were > 55 years old (31%), female (59%), had been diagnosed with hypertension for < 5 years (31%), and received support from family/social environment (40%). Conclusion: Many factors support the adherence to antihypertensive medication, including age, gender, time of hypertension diagnosis, and support from family or social environment. The adherence to antihypertensive medication among patients with hypertension visited Cileunyi Primary Health Care, Bandung District, West Java, Indonesia is good.
Background/Objectives: Studies show that SNPs in ABCB1 rs2032582 and SLCO1B1 rs4149015 affect the PK profile of moxifloxacin, a key drug for MDR-TB. This study aimed to assess the genotype frequencies of ABCB1 rs2032582 and SLCO1B1 rs4149015; describe moxifloxacin AUC0–24 and Cmax; and evaluate the association between genotype variations and moxifloxacin AUC0–24 and Cmax, corrected for the effect of other determinants in MDR-TB patients in Indonesia. Methods: The genotypes were identified using DNA sequencing. Plasma samples for PK analysis were collected at either two or four timepoints post-dose, at steady state. AUC0–24 values were assessed with a limited sampling formula. A multivariate linear regression analysis identified the determinants for moxifloxacin AUC0–24 and Cmax. Results: We recruited 204 MDR-TB patients for PG analysis, with 80 providing PK samples. The majority of the ABCB1 and SLCO1B1 genotypes were wildtype (GG), 41.7% and 93.6%, respectively. The geometric mean AUC0–24 for moxifloxacin was 78.6 mg·h/L and that for Cmax was 6.1 mg/L. No statistically significant difference in exposure to moxifloxacin could be shown between the genotypes. Sex, age, and dose in mg/kg/body weight were significant determinants of the AUC0–24 of moxifloxacin. Conclusions: The major genotype of ABCB1 rs2032582 and SLCO1B1 rs4149015 was wildtype, and the exposure to moxifloxacin was high but not related to the studied genotype in an Indonesian population.