Lack of a pharmacokinetic interaction at steady state between ropinirole and L-dopa in patients with Parkinson's disease.
OBJECTIVE
To assess the interaction between therapeutic dosages of ropinirole and L-dopa plus a decarboxylase inhibitor administered at steady state in patients with Parkinson's disease. DESIGN. Open, 6-week, overlap trial with random allocation.


METHODS
Thirty patients with Parkinson's disease not previously treated with dopamine agonists, of whom 28 produced evaluable pharmacokinetic data for ropinirole and 23 for L-dopa.


METHODS
Group A (14 patients) received L-dopa for weeks 1-5 and ropinirole in increasing increments for weeks 2-6; group B (16) received ropinirole for weeks 1-5 and L-dopa for weeks 5 and 6.


RESULTS
Primary end points were AUC0-8 and Cmax for ropinirole, and AUC0-8, AUC0-infinity and Cmax for L-dopa. Secondary end points were Tmax for ropinirole, and Tmax and half-life for L-dopa. Coadministration with L-dopa at steady state did not affect rate or extent of availability of ropinirole: point estimates of the geometric mean ratio for ropinirole plus L-dopa compared with ropinirole alone for both Cmax and AUC0-8 approximated to unity. The small (16%) increase in peak concentrations of L-dopa on administration with ropinirole is unlikely to be of clinical consequence, as peak concentrations of L-dopa are typically highly variable.


CONCLUSIONS
There are no pharmacokinetic grounds for adjusting dosages of either ropinirole or L-dopa when given in combination.
Division of Drug Metabolism and Pharmacokinetics, SmithKline Beecham Pharmaceuticals, Welwyn, Herts, UK.
A C
AC
Taylor
A
A
Beerahee
D R
DR
Citerone
M J
MJ
Cyronak
T J
TJ
Leigh
K L
KL
Fitzpatrick
A
A
Lopez-Gil
S D
SD
Vakil
E
E
Burns
G
G
Lennox
D000368:Aged; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D002230:Carbidopa / Q000494:pharmacology; D018491:Dopamine Agonists / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007211:Indoles / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007980:Levodopa / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism*
D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D004791:Enzyme Inhibitors; D007211:Indoles; C046649:ropinirole; D007980:Levodopa; D002230:Carbidopa