1 Infectious Diseases, Department of Clinical Research, Det Sundhedsvidenskabelige Fakultet, SDU2 Odense University Hospital3 unknown4 Infectious Diseases, Department of Clinical Research, Det Sundhedsvidenskabelige Fakultet, SDU
Nutritional supplementation to TB patients has been associated with increase weight and mortality reduction, but its effect on the pharmacokinetics of first-line anti-TB drugs is unknown. A cohort of 100 TB patients (58 men, median age 35 (IQR: 29; 40) years and BMI 18.8 (17.3; 19.9) kg/m(2)) were randomized to receiving nutritional supplementation during the intensive phase of TB treatment. Rifampicin plasma concentrations were determined after 1 week and 2 months of treatment. The effects of nutritional supplementation, HIV, time on treatment, body weight, and SLCO1B1 rs4149032 genotype were examined using a population pharmacokinetic model. The model adjusted for body size via allometric scaling, accounted for clearance auto-induction, and detected an increase in bioavailability (+14%) for the patients in the continuation phase. HIV co-infection in patients not receiving the supplementation was found to decrease bioavailability by 21.8%, with a median Cmax and AUC0-24h of 5.6 μg/mL and 28.6 μg⋅h/mL, respectively. HIV co-infected on nutritional supplementation achieved higher Cmax and AUC0-24h of 6.4 μg/mL and 31.6 μg⋅h/mL respectively and only 13.3% bioavailability reduction. No effect of the SLCO1B1 rs4149032 genotype was observed. In conclusion, nutritional supplementation during the first 2 months of TB treatment reduces the decrease in rifampicin exposure observed in HIV co-infected patients, but does not affect exposure in HIV uninfected. If confirmed in other studies, the use of defined nutritional supplementation in HIV co-infected TB patients should be considered in TB control programs.
Antimicrobial Agents and Chemotherapy, 2014, Vol 58, Issue 6, p. 3468-3474