Pharmacokinetics of zidovudine and didanosine during combination therapy

While the combination of zidovudine and didanosine is used in HIV-infected patients with more advanced disease, the possibility of a pharmacokinetic interaction between these two drugs remains controversial. Zidovudine doses of 50, 100, and 200 mg, combined with 67, 167, and 250 mg of didanosine were evaluated in 11 asymptomatic HIV-infected patients after receiving 24 weeks of combination therapy in AIDS Clinical Trials Group protocol 143. The pharmacokinetic parameters of zidovudine and didanosine were similar to those obtained with each drug given as monotherapy in other previously published studies. The renal clearance and urinary recovery of glucuronidated zidovudine was reduced when zidovudine was given in combination with didanosine, possibly due to competition for renal tubular secretion. These data suggest that no clinically important pharmacokinetic interaction occurs when zidovudine and didanosine are given together.