Bioavailability of L-dopa after Madopar HBS administration in healthy volunteers.
Eight healthy male and fasted volunteers received alternatively either one HBS capsule of Madopar 125 or two HBS capsules of Madopar 125 or one standard capsule of Madopar 125 at weekly intervals with and without benserazide pretreatment (50 mg t.i.d. for 6 days). In this trial the Madopar formulations were administered 9.5 h after the last dose of benserazide. Serial blood samples were collected at various time intervals up to 12 h after Madopar dosing. Levodopa plasma concentrations were measured by high-performance liquid chromatography with electrochemical detection. After Madopar HBS without benserazide pretreatment the peak concentration (Cmax) of levodopa was lower and occurred at later times (tmax) than after standard Madopar. The mean values for tmax were 2.4, 2.8 and 0.8 h, whereas those for Cmax were 0.25, 0.56 and 1.38 micrograms/ml for one HBS capsule, two HBS capsules and standard Madopar, respectively. The mean relative bioavailability (versus standard Madopar) was 58 and 67% (value normalized to dose) for one and two HBS capsules, respectively. The parameter of half-value duration (= time span where plasma concentrations are equal to or higher than the half Cmax) was on average 3.5, 3.8 and 0.8 h for one HBS capsule, two HBS capsules and standard Madopar, respectively. Following benserazide pretreatment the mean tmax values for levodopa were 2.8, 2.3 and 0.8 h and the mean Cmax values were 0.35, 0.60 and 1.33 micrograms/ml, respectively, for one HBS capsule, two HBS capsules and standard Madopar. The relative bioavailability (versus standard Madopar) was 57 +/- 14 and 63 +/- 21% (value normalized to dose) for one and two HBS capsules, respectively. The mean values of the half-value duration were 3.6, 4.2 and 1.3 h for one HBS capsule, two HBS capsules and standard Madopar, respectively. For most of the parameters measured, the interindividual variability after Madopar HBS was less pronounced than after standard Madopar. In conclusion, according to these kinetic data, Madopar HBS shows the characteristics of a controlled-release formulation. The reduced bioavailability of the HBS form (60% of that of the standard form) suggests that a higher daily dose of Madopar HBS should be used for clinical practice.
Clinical Research Department, Hoffmann-La Roche, Basle, Switzerland.
C
C
Crevoisier
B
B
Hoevels
G
G
Zürcher
M
M
Da Prada
D000284:Administration, Oral; D000328:Adult; D001545:Benserazide / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D002214:Capsules; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations / Q000493:pharmacokinetics; D006801:Humans; D006834:Hydrazines / Q000493:pharmacokinetics*; D007980:Levodopa / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged
D002214:Capsules; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D006834:Hydrazines; C005177:benserazide, levodopa drug combination; D007980:Levodopa; D001545:Benserazide