Lack of pharmacokinetic interaction between ropinirole and theophylline inpatients with Parkinson's disease

Objective: Ropinirole and theophylline have the potential to interact, beca use they use the same hepatic cytochrome P450 (CYP1A2) as their major metab olic pathway. The present study investigated the effect of steady-state ora l theophylline on the pharmacokinetics of ropinirole at steady state and th e effect of steady-state ropinirole on the pharmacokinetics of a single int ravenous (i.v.) dose of theophylline, both in patients with idiopathic Park inson's disease (PD). Methods: Pharmacokinetic parameters (AUC and C-max) for i.v. theophylline w ere compared before and after a 4-week period of oral treatment with ropini role (2 mg t.i.d.) in 12 patients with PD. Patients were then maintained at this dose of ropinirole, and oral theophylline was co-administered at dose s of up to 300 mg b.i.d. The parameters AUC, C-max and t(max) for ropinirol e were compared before, during and after oral theophylline cotreatment. Results: Go-administration of ropinirole did not significantly change the p harmacokinetics of i.v. theophylline (mean AUC with and without ropinirole: 68.6 mu g . h(-1) . ml(-1) and 70.0 mu g . h(-1) . ml(-1), respectively; m ean C-max with and without ropinirole: 11.07 mu g . ml(-1) and 11.83 mu g . ml(-1): respectively). Similarly, there were no significant changes in rop inirole pharmacokinetics when the drug was co-administered with oral theoph ylline (mean AUC for ropinirole with and without theophylline: 21.91 ng . h (-1) . ml(-1) and 22.09 ng . h(-1) . ml(-1), respectively; mean C-max for r opinirole with and without theophylline: 5.65 ng . ml(-1) and 5.54 ng . ml( -1), respectively; median t(max) for ropinirole with and without theophylli ne: 2.0 h and 1.5 h, respectively). Conclusion: These results suggest a lack of significant pharmacokinetic int eraction between the two drugs at current therapeutic doses.