Lack of interaction between diazepam and nimodipine during chronic oral administration to healthy elderly subjects.
1. Nimodipine (30 mg three times daily) and diazepam (10 mg once daily), were given orally to 24 elderly healthy subjects in a randomized, non-blinded, threefold-crossover study. Each of the three treatment periods lasted 5 days separated by 2 week washout phases. 2. Plasma concentrations of nimodipine and diazepam were not affected by the combined treatment. 3. No clinically relevant changes in haemodynamics, ECG recordings, clinical chemistry or haematology were observed after all of the three treatments. The overall frequency of side effects was lowest during monotherapy with nimodipine and highest during diazepam monotherapy. 4. In the test of subjective rating of tiredness (VAS) and the Pauli calculation test, diazepam, alone and with nimodipine co-medication, produced an increase in tiredness and a clear reduction in performance and endurance. After nimodipine monotherapy an improvement was observed only in the Pauli test. Using the critical flicker fusion frequency test (CFF) significant decrements in performance were found after diazepam monotherapy only. 5. In summary, there was no evidence that either nimodipine or diazepam affected the pharmacokinetics, safety and tolerance of each other. However, the CNS-effects of diazepam were compensated partially by nimodipine.
Heine
P R
PR
AFB Klinische Pharmakologie GmbH, Berlin, Germany.
Weyer
G
G
Breuel
H P
HP
Mück
W
W
Schmage
N
N
Kuhlmann
J
J
D000284:Administration, Oral; D000368:Aged; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D003975:Diazepam / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D005425:Flicker Fusion / Q000187:drug effects; D006207:Half-Life; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009553:Nimodipine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D011594:Psychometrics
D009553:Nimodipine; D003975:Diazepam