[The bioequivalence of two oral propafenone preparations].
The bioequivalence of two oral racemic propafenone (CAS 54063-53-5) preparations was tested in an open, randomised, crossover trial with administration of single doses of 300 mg on two different occasions with a washout period of 7 days. 24 healthy, male volunteers, all proved to be rapid hydroxylators of debrisoquine, were enrolled in the trial. The concentrations of R(+)-, S(-)-propafenone and 5-hydroxypropafenone (5-OH-propafenone) were measured up to 12 h after administration by means of a sensitive and specific HPLC method that allowed the simultaneous quantification of all three substances in plasma. The results of 23 volunteers were evaluated pharmacokinetically. Main target parameters were AUC0-infinity and Cmax of both enantiomers of propafenone. Secondary target parameters were AUC0-infinity and Cmax of 5-OH-propafenone as well as tmax for R(+)- and S(-)-propafenone. The 90% confidence intervals for AUC0-infinity for R(+)-, S(-)-, and 5-OH-propafenone were 0.85-1.07, 0.83-1.10 and 0.84-1.05, respectively. The confidence intervals for Cmax were 0.81-1.12, 0.82-1.17 and 0.87-1.09 for R-, S-, and 5-OH-propafenone, respectively. The concentration maxima of both enantiomers were registered on average 15 min earlier after administration of the test preparation. This difference is of no clinical relevance. Both preparations are bioequivalent according to the criteria of the Committee for Proprietary Medicinal Products (CPMP).
Koytchev
R
R
Cooperative Clinical Drug Research and Development GmbH, Berlin.
Alken
R G
RG
Mayer
O
O
Böhm
R
R
Ellrich
A
A
Waldner-Kölblin
R G
RG
D000284:Administration, Oral; D000328:Adult; D001711:Biotransformation; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D011405:Propafenone / Q000493:pharmacokinetics*; D013237:Stereoisomerism; D013810:Therapeutic Equivalency
D011405:Propafenone