Comparison of two nimodipine formulations in healthy volunteers.
The objective of this study was to assess the pharmacokientic parameters of regular nimodipine (Bayer), 30 mg, given every 6 h and nimodipine AP (nimodipine in micro particles with programmed action contained in tablets, developed by Biocontrolled-Leti Group Laboratories), 120 mg, given every 24 h. Subjects (19 healthy volunteers, five female; 14 male: age: 21 +/- 0.7 years) received one formulation over 5 days. Then, after a washout period of 7 days, the other formulation was given. The analyst was blinded to the relationship in formulation received. Antecubital blood samples were taken before the first tablet was taken and after 15, 45, 60 min and 2, 4, 6, 8, 12, 13, 18 and 24 h on day 1 and five of each formulation. Nimodipine blood levels were analysed by HPLC. At steady-state regular nimodipine reached a C-max of 10.208 +/- 0.317 ng/ml, at a t-max of 1 h; minimum concentration 6 h after dosage was 1.2929 +/- 0.411 ng/ml, half-life was estimated in 2.9 h. Meanwhile nimodipine AP 120 mg reach a C-max of 11.885 +/- 0.403 ng/ml; a t-max of 1 h with a minimum concentration 24 h after the last dose of 4.2387 +/- 0.353 ng/ml (P < 0.001). Apparent half-life was calculated in 17.8 h (P < 0.001). Area under the curve for the 24 h period was 143.76 ng/ml/min for regular nimodipine and 183.7 ng/ml/min for nimodipine AP 120 mg (P < 0.001), indicating better bioavailability. In conclusion nimodipine in AP formulation 120 mg produced similar peak plasma levels (C-max) than regular nimodipine, but with higher trough (C-min) values and stable plasma levels with one administration every 24 h. This formulation would be more suitable when nimodipine chronic therapy is indicated.
Hernández-Hernández
R
R
Clinical Pharmacology Unit, School of Medicine, Universidad Centroccidental Lisandro Alvarado, Barquisimeto, Venezuela. rhernan@cantv.net
Coll
T
T
Rachitzky
P
P
Armas-Hernández
M J
MJ
Armas-Padilla
M C
MC
Velasco
M
M
Rizzo
A
A
D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D009553:Nimodipine / Q000737:chemistry / Q000493:pharmacokinetics*; D013607:Tablets
D002121:Calcium Channel Blockers; D013607:Tablets; D009553:Nimodipine