The influence of levodopa on gastric emptying in man.
1. Simultaneous radioisotopic (99Tc-DTPA) gastric emptying measurements and paracetamol pharmacokinetic studies were performed in eight healthy male volunteers with and without levodopa (125 mg orally). 2. In the absence of levodopa gamma camera imaging showed rapid mono or biexponential emptying in all subjects and the plasma concentration-time curves for paracetamol displayed a single major peak. 3. In the presence of levodopa the time to 90% emptying was prolonged from 32 +/- 24 min to 81 +/- 20 min (P less than 0.01). Gastric emptying was interrupted by a plateau phase in six subjects and this pattern of emptying was associated with double peaks in the plasma concentration-time curves of both levodopa and paracetamol. The time to the end of the plateau phase of emptying correlated with the time to the trough plasma concentrations of paracetamol and levodopa. 4. There was excellent agreement between the plasma concentration-time curves of levodopa and paracetamol, i.e. time to initial peak, r = 0.946, P less than 0.001; time to trough concentration r = 0.943, P less than 0.01; time to second peak r = 0.974, P less than 0.001. 5. The results indicate that levodopa inhibits gastric emptying and thus influences its own absorption. Temporary inhibition of gastric emptying by levodopa (or a metabolite) is the cause of the multiple plasma peaks commonly observed following oral levodopa.
Clinical Pharmacology Group, University of Southampton.
D R
DR
Robertson
A G
AG
Renwick
N D
ND
Wood
N
N
Cross
B S
BS
Macklin
J S
JS
Fleming
D G
DG
Waller
C F
CF
George
D000082:Acetaminophen / Q000493:pharmacokinetics; D000328:Adult; D005746:Gastric Emptying / Q000187:drug effects*; D006207:Half-Life; D006801:Humans; D007980:Levodopa / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D015609:Organotechnetium Compounds; D004369:Pentetic Acid; D016284:Technetium Tc 99m Pentetate
D015609:Organotechnetium Compounds; D000082:Acetaminophen; D007980:Levodopa; D004369:Pentetic Acid; D016284:Technetium Tc 99m Pentetate