Comparative Pharmacokinetics of Kanamycin between Multi-drug Resistant Tuberculosis Patients and Healthy Volunteers

Emergence of MDR-TB has become a global emergency and significant public health problem worldwide. The main problem of second-line anti-TB drugs are high cost, lower efficacy, greater toxicity and prolong treatment required, resulting in low compliance, high defaulter, low sputum conversion and high relapse rate. With DOTS-Plus pilot project being implemented in Myanmar, there is a need to ensure good practice of reserve drugs like Kanamycin, used extensively by the National TB Program, from becoming resistant. Since TB control required an integrated approach, the study explored the socio-demographic, clinical and pharmacokinetic factors that can influence the outcome of treatment. A total of 20 healthy volunteers and 20 MDR-TB patients were recruited for pharmacokinetic study and Kanamycin levels analyzed by bioassay using Bacillus subtilis. The study showed that majority of the MDR-TB recruited were from low education, low income working males with family history of TB contact. Bad habits like smoking, delay in taking proper treatment and poor compliance to DOTS regime was seen in 60% of patients. Comparison with healthy volunteers indicated that MDR-TB patients, although having lower body weight but no significant difference in pharmacokinetic profile, either in bioavailability (AUC; 80.3±35.9vs73.5±26.2µg/hr.ml), distribution (Vd; 49.1±23.1vs46.3±20.2 liters) or elimination (T1/2; 2.3±0.5vs2.1±0.8 hr). Drug levels were well above MIC. All patients tolerate well to treatment. Follow-up for one year showed significant improvement in CXR with 60%of patients having sputum conversion to negativity within 6 months of treatment. This indicated Kanamycin as a safe and effective drug for use in MDR-TB in Myanmar.