BACKGROUND: Low concentrations of anti-tuberculosis drugs are related to drug resistance and treatment failure. OBJECTIVE: To determine the prevalence of low plasma concentrations of anti-tuberculosis drugs. METHODS: The study was performed among 60 pulmonary tuberculosis (TB) in-patients at a tertiary care university-affiliated hospital in Tehran, Iran. Drug samples were drawn 2 and 6 h post dose for isoniazid (INH), rifampicin (RMP) and pyrazinamide (PZA); related concentrations were determined using high-performance liquid chromatography. Plasma drug concentrations, duration of treatment, age, sex, liver enzyme levels, administered doses and smoking status were evaluated and recorded. RESULTS: Among 60 patients recruited to the study, the mean (±SD) age was 54.2 (±20.9) years; 39 were female. The median peak plasma concentrations (C_max) of INH, RMP and PZA were respectively 2.5, 4.0 and 43.6 μg/ml; 81% of the patients had drug plasma concentrations lower than the target ranges for at least one administered drug. Respectively 49.1%, 92.5% and 8.7% of the patients had low concentrations of INH, RMP and PZA. CONCLUSION: The results indicate that RMP concentrations are below the reference range in most patients, while PZA is within the target range of the standard doses.

Matrix-type transdermal delivery systems (TDS) are comprised of the drug dissolved or dispersed in a pressure-sensitive adhesive (PSA) matrix and are designed to provide a controlled delivery through the skin and into systemic circulation. PSAs can directly affect the permeation, release, and performance characteristics of the system. In this study we aimed to design and characterize transdermal delivery systems formulated with lidocaine—as the model drug—loaded in different PSAs, including silicone, polyisobutylene (PIB), and acrylate. TDS containing lidocaine at its saturation points were prepared by the solvent casting method. In vitro permeation studies across dermatomed porcine ear skin were performed using Franz diffusion cells. In vitro release studies were carried out using USP apparatus 5 (paddle over disk). The cumulative amount permeated from the acrylate was significantly higher than silicone and PIB. The acrylate TDS contained a ten times higher drug amount than silicone TDS, but the permeation flux was only two folds higher. Results also showed the release of drug does not linearly correlate to saturation, as the silicone TDS comprising of the lowest amount of drug loading, showed the highest percentage release indicating the choice of PSA affected the drug release and permeation profile.

Therapeutic Drug Monitoring (TDM) of first-line anti-tuberculosis (TB) drugs is a decisive tool, allowing the clinician to successfully treat TB patients. The objective of the study was to develop and optimize a simple, sensitive, and reliable high-performance liquid chromatography (HPLC) method for the simultaneous determination of isoniazid (INH), pyrazinamide (PZA), and rifampin (RIF) levels in human plasma. Nicotinamide was used as the internal standard and the samples were prepared after protein precipitation using acetonitrile and zinc sulfate. The separation was achieved using a C18 reversed-phase applying gradient elution. The mobile phase was a combination of water–methanol solution with a ratio of 95:05 (v/v) at the initial phase. All calibration curves had good linearity (r2 > 0.99) and the inter- and intra-day RSDs were lower than 15%. The limit of detection with a signal-to-noise ratio (S/N) of 3:1 was 0.16, 0.5, and 0.33 μg mL–1 for INH, PZA, and RIF, respectively. The method presented here was selective, sensitive, and reproducible, and could be used for‌ therapeutic drug monitoring in the patients who were under treatment with these drugs.

Lack of a safe and convenient disposal method for expired and unused medications may lead to many problems such as accidental exposure, intentional misuse, and food and water contamination. Activated carbon can offer safe disposal of medications due to its highly porous structure, which exerts strong physical adsorption forces with chemicals. This study aimed to evaluate the efficiency of an activated carbon-based drug disposal system for deactivating three model sedative prescription medications. Deactivation was performed by mixing the medication, activated carbon, and tap water. Desorption was evaluated by exposing the deactivation system to wash-out solutions. Rapid, precise, accurate, and sensitive HPLC-UV method for each drug was successfully developed, validated and employed. Results of the 28-day deactivation study showed that on average, more than 94.00% of drugs were rapidly deactivated within 8 hours. All drugs reached more than 99.00% deactivation by the end of 28-day period. Desorption study demonstrated that all medications were retained by the system, with insignificant amount of drug (0.25%) leached into the washout solutions within 24 hours. In conclusion, activated carbon rapidly and successfully deactivated the medications tested, suggesting activated carbon-based drug disposal system provides a convenient, secure, and effective method for unused medication.