RT Journal Article
SR Electronic
T1 Pharmacokinetic study of isoniazid and pyrazinamide in children: impact of age and nutritional status
JF Archives of Disease in Childhood
JO Arch Dis Child
FD BMJ Publishing Group Ltd and Royal College of Paediatrics and Child Health
SP 1150
OP 1154
DO 10.1136/archdischild-2017-313910
VO 103
IS 12
A1 Dayal, Rajeshwar
A1 Singh, Yatish
A1 Agarwal, Dipti
A1 Kumar, Manoj
A1 Swaminathan, Soumya
A1 Ramachandran, Geetha
A1 Kumar, Santosh
A1 Narayan, Shamrendra
A1 Goyal, Ankur
A1 Kumar, A K Hemant
YR 2018
UL http://adc.bmj.com/content/103/12/1150.abstract
AB Objectives To evaluate pharmacokinetics of first-line antitubercular drugs, isoniazid (INH) and pyrazinamide (PZA), with revised WHO dosages and to assess its adequacy in relation to age and nutritional status.Design Observational study.Setting This study was conducted at Sarojini Naidu Medical College, Agra, and National Institute for Research in Tuberculosis, Chennai.Patients 40 subjects diagnosed with tuberculosis were registered in the study and started on daily first-line antitubercular regimen based on the revised WHO guidelines.Interventions Blood samples were collected at 0, 2, 4, 6 and 8 hours from these subjects after 15 days of treatment for drug estimations.Main outcome measure The measurement of drug concentrations (maximum peak concentration (Cmax) and area under the time –concentration curve (AUC0–8 hours)) for INH and PZA. Appropriate statistical methods were used to evaluate the impact of age and nutritional status on pharmacokinetic variables.Results For INH, the difference in drug exposures in children <3 years (Cmax 3.18 µg/mL and AUC0–8 hours15.76 µg/mL hour) and children >3 years (Cmax3.05 µg/mL and AUC0–8 hours 14.37 µg/mL hour) was not significant (P=0.94, P=0.81, respectively). The drug levels in children with low body mass index (BMI) (Cmax3.08 µg/mL; AUC0–8 hours14.81 µg/mL hour) were also comparable with their normal counterparts (Cmax3.09 µg/mL, P=0.99; AUC0–8 hours 14.69 µg/mL hour, P=0.82). PZA drug exposures obtained in children less than 3 years (Cmax29.22 µg/mL, AUC0–8 hours 155.45 µg/mL hour) were significantly lower compared with drug levels in children above 3 years (Cmax 37.12 µg/mL, P=0.03; AUC 202.63 µg/mL hour, P value=0.01). Children with low BMI had significantly lower drug concentrations (Cmax 31.90 µg/mL, AUC0–8 hours167.64 µg/mL hour) when compared with normal counterparts (Cmax 37.60 µg/mL, P=0.02; AUC0–8 hours 208.77 µg/mL hour, P=0.01).Conclusions The revised WHO drug dosages were found to be adequate for INH with respect to age and nutritional status, whereas PZA showed significantly lower drug levels in children <3 years and in malnourished children.