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 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.