title: Effect of a macrolide (spiramycin) on the pharmacokinetics of L-dopa and carbidopa in healthy volunteers.
abstract: In one well-equilibrated parkinsonian patient treated with combined L-dopa and carbidopa (Sinemet), we have observed changes in treatment efficacy while receiving spiramycin (Rovamycine) for an intercurrent respiratory infection. A preliminary study of the pharmacokinetics of L-dopa and its main metabolites 3-O-methyldopa (3-OMD) and dihydroxyphenylacetic acid (dopac) in two parkinsonian patients treated with Sinemet has revealed a marked decrease in the AUC0-360 of these two metabolites after a 3-day course of Rovamycine. In order to confirm this interaction, we have studied the modifications of the pharmacokinetics of L-dopa, 3-OMD, dopac, and carbidopa in eight male healthy volunteers after a single dose of Sinemet 250 (L-dopa, 250 mg and carbidopa, 25 mg) before and after a 3-day course of Rovamycine. Our study confirms this interaction. After spiramycin, we observed a marked reduction in AUC0-360 for L-dopa (p less than 0.001), 3-OMD (p less than 0.001), and carbidopa (p less than 0.001), and an increase in AUC0-360 for dopac (p less than 0.01). The L-dopa elimination half-life was increased (p less than 0.012); differences in peak plasma concentrations did not attain statistical significance. We think that these modifications in L-dopa pharmacokinetics after spiramycin are due to nonabsorption of carbidopa secondary to modified gastrointestinal motility.
authors.affiliation: Unité de Thérapeutique, Centre Hospitalier de Versailles, Le Chesnay, France.
authors.forename: N
authors.initials: N
authors.lastname: Brion
authors.forename: K
authors.initials: K
authors.lastname: Kollenbach
authors.forename: M H
authors.initials: MH
authors.lastname: Marion
authors.forename: A
authors.initials: A
authors.lastname: Grégoire
authors.forename: C
authors.initials: C
authors.lastname: Advenier
authors.forename: M
authors.initials: M
authors.lastname: Pays
mesh_terms: D000328:Adult; D002230:Carbidopa / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D007980:Levodopa / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D015572:Spiramycin / Q000494:pharmacology*
chemical_list: D007980:Levodopa; D015572:Spiramycin; D002230:Carbidopa