Objective: Ropinirole and theophylline have the potential to interact, because they use the same hepatic cytochrome P450 (CYP1A2) as their major metabolic pathway. The present study investigated the effect of steady-state oral theophylline on the pharmacokinetics of ropinirole at steady state and the effect of steady-state ropinirole on the pharmacokinetics of a single intravenous (i.v.) dose of theophylline, both in patients with idiopathic Parkinson's disease (PD).
Methods: Pharmacokinetic parameters (AUC and Cmax) for i.v. theophylline were compared before and after a 4-week period of oral treatment with ropinirole (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 doses of up to 300 mg b.i.d. The parameters AUC, Cmax and tmax for ropinirole were compared before, during and after oral theophylline co-treatment.
Results: Co-administration of ropinirole did not significantly change the pharmacokinetics of i.v. theophylline (mean AUC with and without ropinirole: 68.6 micog x h(-1) x ml(-1) and 70.0 microg x h(-1) x ml(-1), respectively: mean Cmax with and without ropinirole: 11.07 microg x ml(-1) and 11.83 microg x ml(-1), respectively). Similarly, there were no significant changes in ropinirole pharmacokinetics when the drug was co-administered with oral theophylline (mean AUC for ropinirole with and without theophylline: 21.91 ng x h(-1) x ml(-1) and 22.09 ng x h(-1) x ml(-1), respectively; mean Cmax for ropinirole with and without theophylline: 5.65 ng x ml(-1) and 5.54 ng x ml(-1), respectively; median tmax for ropinirole with and without theophylline: 2.0 h and 1.5 h, respectively).
Conclusion: These results suggest a lack of significant pharmacokinetic interaction between the two drugs at current therapeutic doses.