ABSTRACT
BACKGROUND: Previous pharmacokinetic trials with standard levodopa formulations showed a different behaviour of levodopa degradation in plasma of patients with Parkinson's disease (PD) in various stages. OBJECTIVES: To investigate associations between levodopa plasma levels in relation to the scored intensity of PD. SUBJECTS AND METHODS: We administered water soluble 100 mg levodopa and 25 mg benserazide to 50 PD patients, taken off medication for at least 12 hours, and assessed the levodopa plasma concentrations during an 180 minutes period under standardised conditions. RESULTS: The computed area under the curve (AUC) values of levodopa plasma levels were significant higher in advanced PD patients. PD rating scores significantly correlated to the AUC outcomes and the maximum levodopa plasma concentration. CONCLUSIONS: Levodopa availability improves with progression of PD. This may result from deteriorated peripheral activity of levodopa metabolising enzymes or an increasing enteric dysfunction with subsequent better duodenal levodopa absorption or both.
Subject(s)
Antiparkinson Agents/blood , Levodopa/blood , Parkinson Disease/blood , Adult , Aged , Aged, 80 and over , Analysis of Variance , Antiparkinson Agents/therapeutic use , Area Under Curve , Chromatography, High Pressure Liquid , Disease Progression , Female , Humans , Levodopa/therapeutic use , Male , Middle Aged , Parkinson Disease/drug therapy , Severity of Illness Index , Statistics as Topic , Time FactorsABSTRACT
1. Noninvasive tests for the staging of chronic hepatitis C virus (HCV) infection would be an attractive alternative to liver biopsy. The 13C-aminopyrine breath test (ABT) has been proposed for the noninvasive assessment of hepatic function and partly correlates with fibrosis. We aimed to investigate causes for the lack of discriminatory power for different degrees of hepatic fibrosis. 2. Eighty-three patients (median age 49 years (28-78 years)) with chronic HCV infection underwent the ABT after an oral load of 75 mg N,N-dimethyl-13C-aminopyrine. Portal vein flow was assessed by duplex-Doppler and a laboratory index (aspartate aminotransferase to platelet ratio index or APRI) was calculated. Parameters were compared with liver histology. 3. The cumulative 13C-recovery differed significantly between patients without relevant fibrosis (fibrosis score 0-2) and cirrhosis (5-6), beginning after 30 min of sampling (P < 0.05). The ABT did not discriminate patients with fibrosis scores 3-4 from the remaining two patient groups. Sensitivity and specificity for the prediction of cirrhosis was 73.4-82.8% and 63.2-68.4%, depending on the sampling time. Compared with the fibrosis score (P = 0.04), patient age was a highly significant independent predictor for the 13C-recovery (P < 0.0001). Aspartate aminotransferase to platelet ratio index and duplex-Doppler predicted cirrhosis with 76.6%vs. 87.5% sensitivity and 63.2%vs. 68.4% specificity. 4. Our data suggest an age-dependent decrease of cytochrome P450 activity which probably accounts for the large overlap of ABT results that preclude clear differentiation. This is also consistent with former pharmacodynamic trials. Age-adapted reference ranges could improve ABT results.
