The effect of age on the pharmacokinetics of levodopa administered alone and in the presence of carbidopa.
1. The effect of age on the pharmacokinetics of levodopa administered alone and in the presence of carbidopa was investigated in young and elderly healthy volunteers. 2. The plasma clearance of levodopa following intravenous administration of 50 mg was 14.2 +/- 2.8 (s.d.) ml min-1 kg-1 in the elderly compared with 23.4 +/- 4.1 ml min-1 kg-1 in the young (P less than 0.01) which resulted in a 49% greater area under the plasma concentration-time curve (AUC) in the older subjects (P less than 0.01). The volume of distribution (Vss) was lower in the elderly (1.01 +/- 0.29 l kg-1) than in the young (1.65 +/- 0.39 l kg-1) (P less than 0.002). 3. Following oral administration of 250 mg of levodopa the AUC was 2512 +/- 588 ng ml-1h in the elderly compared with 1056 +/- 282 ng ml-1h in the young (P less than 0.002). Cmax was also significantly greater in the elderly (P less than 0.05). The bioavailability of levodopa was significantly greater in the elderly (0.63 +/- 0.12 compared with 0.41 +/- 0.16, P less than 0.01). 4. In the presence of carbidopa, the plasma clearance of intravenous levodopa (50 mg) was reduced in both age groups but remained lower in the elderly (5.8 +/- 0.9 ml min-1 kg-1 compared with 9.3 +/- 1.0 ml min-1 kg-1; P less than 0.01). This resulted in a 54% greater AUC in the older subjects (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Clinical Pharmacology Group, University of Southampton, Southampton General Hospital.
D R
DR
Robertson
N D
ND
Wood
H
H
Everest
K
K
Monks
D G
DG
Waller
A G
AG
Renwick
C F
CF
George
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D002230:Carbidopa / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007980:Levodopa / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male
D007980:Levodopa; D002230:Carbidopa