Helicobacter pylori‐induced reduction of acute levodopa absorption in parkinson's disease patients

We occasionally observed a consistent clinical improvement in an advanced Parkinson’s disease (PD) patient (Hoehn and Yahr [H and Y], stage 4, 10-year disease history) under stable levodopa (L-dopa) therapy, immediately after eradicating Helicobacter pylori (Hp) infection. We hypothesised that Hpinduced changes of the gastric environment (ie, pH variations or increase of oxidant agents) affecting L-dopa absorption might be reversed by eradicating Hp infection. Therefore, we measured the acute plasma L-dopa concentration–time curve in 7 advanced PD patients (mean age, 70.4 6 6.3 years; mean disease duration, 6.8 6 2.4 years; H and Y $ 2.5) who were Hp-positive (IgG antibody titer higher than 1,000 Pyloryset; Orion Diagnostica, Espoo, Finland), and had no history of previous Hp eradication attempts. Measurements were made in a blind fashion at baseline, 1 week after a 7-day cycle with placebo and 1 week after a standard cycle of a 7-day therapy with omeprazole, amoxicillin, and chlarithromycin. In each condition studied, plasma L-dopa concentration was monitored every 0.5 hour up to 4.0 hours, beginning with a fasting oral dose of L-dopa (250mg Sinemet) administered after an overnight withdrawal. L-dopa blood content was determined by highperformance liquid chromatography coupled to electrochemical detection. Data are expressed as mean 6 standard error. Area under the concentration time curve (AUC) was calculated for each patient, each acting as his or her own control, using the Pharmacologic Calculation System v 4.0 according to the trapezoidal rule. Patient clinical scores were evaluated by a blinded neurologist using the Unified Parkinson’s Disease Rating Scale (UPDRS) motor examination III (min, 0; max, 108). The clinical score was assessed immediately before L-dopa administration and then repeated at 1 and 2-hour intervals thereafter (Table). The mean AUC significantly increased after antibiotic therapy from 6,584.7 6 830.2 to 7,871.0 6 1,169.5ng/mL (p , 0.01, two-way analysis of variance [ANOVA] for repeated measures; factor interaction: treatment [pre/post] vs drugs, placebo/antibiotic therapy; posthoc Tukey test, p , 0.05) but not after placebo (from 6,584.7 6 830 to 6,624.3 6 970ng/mL; Fig, insets). Single values of the plasma L-dopa concentration–time curves showed no significant variations (three-way ANOVA). However, after antibiotic therapy, L-dopa levels seemed to increase mostly at late intervals (.1.5 hours; see Fig; A). In fact, the expected L-dopa-induced antiparkinsonian effect over the following 2 hours (p , 0.01, Friedman ANOVA) was significantly larger after antibiotic therapy than after placebo only at the second hour (UPDRS III, 23.1 6 8.8 vs 33.9 6 10.7; p , 0.01, Wilcoxon test). These data suggest that Hp infection may interfere with L-dopa absorption in PD patients. Moreover, they indicate that Hp eradication procedure may increase drug availability by about 20%, prolonging the tail of the plasma L-dopa conFig. Effects of (A) placebo or (B) antibiotic treatment on L-dopa plasma concentrations in Parkinsons’s disease patients affected by HP infection.