What are the side effects of taking Prozac and Primidone along with Elavil?
Steady-state kinetics of fluoxetine and amitriptyline in patients treated with a combination of these drugs as compared with those treated with amitriptyline alone
A el-Yazigi, K Chaleby, A Gad, and DA XXXXXXX
The steady-state kinetics of amitriptyline (AMI), fluoxetine (FLU), and their active metabolites nortriptyline (NTRIP) and norfluoxetine (NFLU) were studied in 15 patients treated once daily for long durations with 50 mg of AMI and 20 mg of FLU. These compounds were analyzed simultaneously in plasma by liquid chromatography. The means and (SEM) of the steady-state concentrations (Css) of AMI, NTRIP, FLU, and NFLU were 80.6 (14.2), 52.6 (10.3), 85.3 (16.1), and 90 (13.6) ng/mL, respectively, and the apparent oral clearances (CLor) of AMI and FLU were 42.4 (8.6) and 14.9 (2.5) L/hr, respectively. The metabolite/drug steady-state concentration ratio (Css(m)/Css) for NTRIP/AMI was 0.75 (0.14) and for NFLU/FLU was 1.27 (0.17). There was a significant correlation (P < 0.05) between Css of FLU and that of AMI or NTRIP. The Css and Css(m)/Css values obtained for AMI were higher (P < 0.056 and P < 0.0034, respectively) than those we observed in 10 patients treated solely with the same dose of AMI. The twofold increase in Css of AMI and ninefold increase in Css of NTRIP seem to be the result of inhibition of the metabolism of these compounds by FLU, particularly the ring hydroxylation. Norfluoxetine may have a small inhibitory influence on the metabolism of NTRIP but lacks this effect on the metabolism of AMI.
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My name is Dr Muhammad Ali Rauf & i will look into your problem.
I have gone through your query and would try to help you in the best possible way.
A drug when taken, goes to blood and performs its action till the time it remains in the blood. After particular time that drug gets metabolized by certain enzymes which mostly are present in the liver. Some drugs particularly effect those enzymes as a result their metabolism is delayed and effect prolongs. This study is basically showing the effect of norfluoxetine on other drugs like amitriptyline, fluoxetine and their active metabolites nortriptyline. Norfluoxetine decreases the metabolism of above mentioned drugs so we give dose less than the required at that specific time and then gradually increase till necessary results are achieved.
Now about your question:
1. Drug concentration can be evaluated by performing blood test. Particular drug is given and then its levels are checked in the blood after specific time through drug's half life.
2. Yes, phenobarbital is an enzyme inducer, it significantly increases the metabolism of amitriptyline through particular enzyme as a result it gets out of the body earlier so close monitoring is required. It is difficult to give reading as how much it effects because it varies from person to person. As mentioned earlier, you can get it monitored by visiting hospital and undergoing blood test. If you are not getting the required results from that medicine then it means that its levels are less than the required one. If you are doing fine with your day to day life then you need not to worry and continue same dose.
Hope I have answered your query. If you have any further questions I will be happy to help if not then don't forget to close the discussion and rate it.
Wishing you good health !!
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