Aim To observe the plasma concentrations and pharmacokinetic-pharmacodynamic (PK-PD) profile of first-line antitubercular drugs in pulmonary tuberculosis (TB) patients with and without diabetes mellitus (DM). Methods Newly diagnosed pulmonary TB patients aged 18-60 with or without DM were included in the study. Group I (n = 20) included patients with TB, whereas Group II (n = 20) contained patients with TB and DM. After 2 weeks of therapy, plasma concentrations and other PK-PD parameters were determined. The improvement in clinical features, X-ray findings, sputum conversion and adverse drug reactions (ADRs) were measured after 2 months of ATT. Results Isoniazid displayed non-significantly higher plasma concentrations in diabetic patients, along with a significantly (P < 0.05) longer elimination half-life (t1/2). Rifampicin plasma concentration at 4, 8, and 12 h were significantly (P < 0.05) lower and it displayed significantly (P < 0.05) lower area under curves (AUC0-12 and AUC0-), shorter t1/2, higher clearance (Cl) and a lower AUC0-/MIC ratio in diabetic patients. Pyrazinamide and ethambutol showed non-significantly higher plasma concentrations, AUC0-12, AUC0-, and t1/2 in diabetic patients. The improvement in clinical features, X-ray findings, sputum conversion, and ADRs were comparable in both the groups. Conclusions The presence of DM in TB patients affects the PK-PD parameters of isoniazid, rifampicin, pyrazinamide and ethambutol variably in the Indian population. Studies in a larger number of patients are required to further elucidate the role of DM on the PK-PD profile of first-line antitubercular drugs and treatment outcomes in TB patients with concomitant DM.

Background and aims: Oral mucositis (OM) is common and distressing toxicity in children on chemotherapy. There is limited number of safe and effective therapeutic options available for OM. Ketamine oral rinse has shown promising results in few studies in adults. This randomized, double-blind placebo-controlled trial aimed to test the efficacy of ketamine mouthwash in reducing chemotherapy-induced severe OM pain in children. Methods: Children aged 8-18 years with severe OM were randomized to a single dose of ketamine mouthwash (4 mg/ml solution; dose 1 mg/kg) or a placebo. A sample size of 44 patients was determined. Pain score (6-point faces scale) was noted at baseline and 15, 30, 45, 60, 120, 180, and 240 min. The outcome variables were a reduction in pain score, need for rescue medications, and adverse events. Results: The baseline characteristics were comparable in the two groups. The mean OM pain at 60 min decreased by 1.64 points (CI 1.13-2.14) in the ketamine group and 1.32 points (CI 0.76-1.87) in the placebo group (p=0.425), with a group difference of 0.32 points. Rescue pain medication (at 60 min) was required in 13.6% in the ketamine group and 18.2% in the placebo group (p=1.000). There were no significant adverse events observed. Conclusions: Among children on cancer chemotherapy with severe OM, ketamine mouthwash at a dose of 1 mg/kg did not significantly reduce OM pain. It did not decrease the need for rescue pain medications. Further research is warranted to test higher doses of ketamine for a clinically significant effect.