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

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 C_max) 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, C_max and t_max 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 μg · h⁻¹ · ml⁻¹ and 70.0 μ· h⁻¹ · ml⁻¹, respectively; mean C_max with and without ropinirole: 11.07 μ g · ml⁻¹ and 11.83 μg · 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 · h⁻¹ · ml⁻¹ and 22.09 ng · h⁻¹ · ml⁻¹, respectively; mean C_max for ropinirole with and without theophylline: 5.65 ng · ml⁻¹ and 5.54 ng · ml⁻¹, respectively; median t_max 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. Received: 10 August 1998 / Accepted in revised form: 27 January 1999