Didanosine systemic exposure in children similar with or without food, high interpatient variability suggests TDM to titrate individual dosages
The systemic exposure of the HIV nucleoside analogue didanosine is similar in children regardless of whether the drug is given with or without food, according to a study in the March 20th issue of AIDS Research and Human Retroviruses.
‘From the adult literature it’s been shown that when didanosine is given with food, the amount that’s absorbed is substantially decreased,’ Dr. Robert C. Stevens of the University of Tennessee, in Memphis, told Reuters Health. ‘But for infants and toddlers, to adhere to schedules of taking medication either with food or without food presents logistic difficulties.’
To look at the effect of food on didanosine absorption in children, Dr. Stevens and colleagues from the Pediatric AIDS Clinical Trials Group Protocol 144 Study Team randomised 106 symptomatic HIV-infected children, aged 3 months to 18 years, to one of two oral doses of didanosine every 12 hours.
The researchers measured various pharmacokinetic parameters on one visit, in which the patient fasted 2 hours before and 1 hour after didanosine administration, and on another visit, in which the patient had a normal breakfast 10 minutes before drug administration.
Seventy-seven patients were evaluable at the final analysis. Although the presence of food significantly reduced didanosine absorption, the overall systemic exposure, as illustrated by the area under the curve, was similar with recent food consumption and with fasting. This was explained by the fact that ‘the lower fraction absorbed with food was offset by the absorption rate becoming rate limiting for elimination,’ they report.
Why the results in children were different from adults is not clear. But Dr. Stevens pointed out that the adult studies used standardized meals to control for diet, which does not represent typical eating patterns.
‘I think what this reflects is that children don’t eat standardized meals all the time. Perhaps in a well-controlled regulated research environment, there may have been a different outcome,’ he said. But with the typical eating patterns of children, ‘it appears that there is no impaired bioavailability of didanosine when taken with food.’
‘It doesn’t complicate the dosing regimen for the caretaker of the child,’ he pointed out. ‘They can give the didanosine without regard to food.’
There was also more interpatient variability in the pharmacokinetics and higher clearance of the drug compared with adults, which ‘would suggest that children may need higher doses compared to adults,’ he added.
In adults, administration with food appears to increase the likelihood of gastrointestinal upset and diarrhoea, due to the antacid buffer. PK studies of enteric coated ddI with or without food in children should now be performed as this formulation nears marketing approval in Europe.
AIDS Res Hum Retroviruses 2000;16:415-421. Source: Reuters Health