Gastric emptying in healthy volunteers after multiple doses of levodopa.
1. Oral levodopa frequently produces an episodic delay in gastric emptying which leads to multiple peak concentrations of the drug in plasma. We have studied the effects of multiple dosing of levodopa on gastric emptying and levodopa absorption in eight healthy young volunteers in a randomised two-way cross-over study. 2. The plasma concentration-time curves for levodopa were measured after three oral doses of 125 mg given at 2 h intervals and compared with the concentration-time curve for levodopa following administration of two doses of placebo and a single oral dose of 125 mg. 3. A low incidence of multiple peak plasma concentrations of levodopa was detected after all doses of levodopa. The area under the plasma concentration-time curves (AUC) for the final dose of levodopa (150.8 +/- 22.0 micrograms ml-1 min) was lower than for the two preceding doses (205.7 +/- 41.8 and 199.5 +/- 51.8 micrograms ml-1 min) but not different from that of the single dose given at the same time of day (141.7 +/- 29.1 micrograms ml-1 min). This indicates that the lower AUC of the final dose of levodopa was related to the time of administration and not a result of the two preceding doses. 4. The absence of any significant effects of preceding doses of levodopa on gastric emptying was confirmed a) by co-administration of soluble paracetamol, as a marker of gastric emptying, with the second dose of levodopa or placebo and b) by co-administration of radiolabelled DTPA and gamma-camera imaging with the final dose of levodopa on the multiple dosing day and the single dose of levodopa on the placebo day.(ABSTRACT TRUNCATED AT 250 WORDS)
Waller
D G
DG
Clinical Pharmacology Group, Southampton General Hospital.
Roseveare
C
C
Renwick
A G
AG
Macklin
B
B
George
C F
CF
D000082:Acetaminophen / Q000097:blood / Q000493:pharmacokinetics; D000284:Administration, Oral; D000328:Adult; D004311:Double-Blind Method; D005746:Gastric Emptying / Q000187:drug effects*; D006207:Half-Life; D006801:Humans; D007980:Levodopa / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D011897:Random Allocation
D000082:Acetaminophen; D007980:Levodopa