Pharmacogenetic testing for NAT2 genotypes in a Tanzanian population across the lifespan to guide future personalized isoniazid dosing.

Despite updated recommendations for weight-based isoniazid dosing in children with drug-susceptible tuberculosis (TB) and higher dose isoniazid in regimens for adults with drug-resistant TB, individual pharmacokinetic variability can lead to sub-target isoniazid exposure. Host pharmacogenetics and isoniazid exposure remain understudied, especially in the East African population. We therefore employed a real-time polymerase chain reaction (qPCR) assay system to test genomic DNA extracted from saliva samples targeting the NAT2 gene responsible for isoniazid metabolism to describe the frequency of human single nucleotide polymorphisms in NAT2 within populations of children and adults in Tanzania, ascribe those polymorphisms to acetylator phenotype, and correlate to serum isoniazid exposures. In adults treated with higher dose isoniazid, genotypes with a predicted allelic phenotype of slow or intermediate acetylation were able to achieve a 0.41 µg/mL higher Cmax (p = 0.018) and a 2.9h*µg/mL higher AUC0-12 (p = 0.003) per mg/kg increase in isoniazid dosage versus adults with rapid acetylation phenotype. A similar relationship was not found in the younger age population as predicted by timing of NAT2 maturation. This saliva based qPCR assay was fieldable to guide personalized isoniazid dosing in adults but not young children that may not have full NAT2 maturation and activity.

Phytochemical Investigation, Antioxidant and Antimycobacterial Activities of Schkuhria pinnata (Lam) Thell Extracts Against Mycobacterium smegmatis.

The focus of this study was to evaluate the antioxidants and antimycobacterial activities of extracts of Schkuhria pinnata. Serial exhaustive extraction procedure was employed using solvents of varying polarity to obtain the desired extracts. Thin layer chromatography and standard chemical tests were used to analyze phytochemicals constituents. Free radical scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH) methods were used to detect the presence of antioxidant compounds. Antimycobacterial activity was evaluated using microdilution and bioautography assays. A variety of secondary metabolites such as flavonoids, tannins, and alkaloids were detected in the extract. Ethyl acetate and acetone extracts had high antioxidant activity on chromatograms eluted in ethyl acetate/methanol/water while methanol extract at various concentrations had the best scavenging activity. The minimum inhibitory concentration (MIC) values ranged from 0.02 to 2.50 mg/mL. Total phenol content was 55.33 ± 3.51 mg of gallic acid equivalent (GAE)/g and higher when compared with flavonoids (4.00 ± 0.35 mg of quercetin equivalent [QE]/mg) and tannin content (28.00 ± 1.73 mg of GAE/g). The most effective antimycobacterial activity against Mycobacterium smegmatis was observed with the lowest inhibitory concentrations of acetone (0.27 mg/mL), dichloromethane (0.32 mg/mL), and ethyl acetate (0.32 mg/mL) in that order. In massive extraction, hexane and dichloromethane had the greatest inhibitory bands on benzene/ethanol/ammonium hydroxide bioautograms. Antimmycobacterial activity gives promising potential leads of S pinnata extracts to be used in the development of antimycobacterial drugs. The presence of antioxidant and antimycobacterial compounds requires further isolation and purification.