Steady-state pharmacokinetics of nimodipine during chronic administration of indometacin in elderly healthy volunteers
Mück, W.; Heine, P.R.; Schmage, N.; Niklaus, H.; Horkulak, J.; Breuel, H.P.
Arzneimittel-Forschung 45(4): 460-462
1995
ISSN/ISBN: 0004-4172 PMID: 7779142 Document Number: 449082
The possible influence of chronic indometacin (CAS 5386-1) medication on nimodipine (CAS 66085-59-4) pharmacokinetics was investigated in 24 elderly healthy subjects. Both drugs were orally administered in a nonblinded, randomized, twofold crossover design. The study periods with a 5-day treatment each were separated by a 2-week washout period The C-ss, max of nimodipine was increased after the combined administration of nimodipine(30 mg t.i.d.) and indometacin (25 mg bid) as compared with those after nimodipine monotherapy: 24.2 +- 14.7 mu-g/l vs. 19.7 +- 10.3 mu-g/l. This increase, however was not of an order to become clinically relevant. Nimodipine AUC-ss slightly increased under indometacin co-medication from 57.9 +- 27.5 mu-g cntdot h cntdot l-1 to 62.8 +- 26.6 mu-g cntdot h cntdot l-1, resulting in a mean relative bioavailability of nimodipine of 111% with a 90%-confidence interval of 96-128% for the combined medication. There was no evidence of any clinically relevant difference in hemodynamics and other findings between both treatments. The overall frequency of side effects was low after both medication regimens. The findings of this study indicate that a combined treatment with both compounds should not be associated with a clinically relevant interaction.