Imipramine pharmacokinetics

Abernethy DR, Divoll M, Greenblatt DJ, Shader RI. Imipramine pharmacokinetics and absolute bioavailability effect of food ClinRes (1983) 31, 626A,... 

A 15-day study in 591 patients, to assess the effects of the concurrent use of acamprosate with other drugs eommonly used in the management of alcohol withdrawal, found no evidence of additional adverse effeets with meprobamate, oxazepam, or the barbiturate complex tetrabamate (that includes phenobarbital). Other studies found that acamprosate eaused no clinically relevant ehanges in imipramine pharmacokinetics, and the pharmacokinetics of both diazepam and acamprosate were unchanged by concurrent use. ... 

Ciraulo DA, Jaffe JH Tricyclic antidepressants in the treatment of depression associated with alcoholism. Clin Psychopharmacol 1 146—150, 1981 Ciraulo DA, Nace E Benzodiazepine treatment of anxiety or insomnia in substance abuse patients. Am J Addict 9 276—284, 2000 Ciraulo DA, Barnhill JG, Jaffe JH, et al Intravenous pharmacokinetics of 2-hydroxy-imipramine in alcoholics and normal controls. J StudAlcohol 51 366-372, 1990 Ciraulo DA, Knapp CM, LoCastro J, et al A benzodiazepine mood effect scale reliability and validity determined for alcohol-dependent subjects and adults with a parental history of alcoholism. Am J Drug Alcohol Abuse 27 339—347, 2001 Collins MA Tetrahydropapaveroline in Parkinson s disease and alcoholism a look back in honor of Merton Sandler. Neurotoxicology 25 117-120, 2004 COMBINE Study Research Group Testing combined pharmacotherapies and behavioral interventions in alcohol dependence rationale and methods. Alcohol Clin Exp Res 27 1107-1122, 2003a... 

Compared to antipsychotics, there are even fewer studies on the prescribing patterns of antidepressants done in Asian countries. Pi etal. (1985) conducted a survey of psychotropic prescribing practices reported by psychiatrists in 29 medical schools in 9 Asian countries. Daily dose range of tricyclic antidepressants (TCAs) such as amitriptyline, imipramine, and nortriptyline in Asian countries was comparable to the practice in USA. This is despite differences found between Asian and non-Asian populations in the pharmacokinetics of TCAs (Pi et al, 1993). A questionnaire on the practical prescribing approaches in mood disorders administered to 298 Japanese psychiatrists was reported by Oshima et al. (1999). As first-line treatment, the majority of respondents chose newer TCAs or non-TCAs for moderate depression and older TCAs for severe depression. Combination of antidepressants and anxiolytics was preferred in moderate depression, while an antidepressant and antipsychotic combination was common in severe psychotic depression. Surprisingly, sulpiride was the most favored drug for dysthymia. In a naturalistic, prospective follow-up of 95 patients with major depression in Japan, the proportion of patients receiving 125 mg/day or less of imipramine was 69% at one month and 67% at six months (Furukawa et al., 2000). 

Imipramine, a TCA, was the first pharmacological agent noted to treat panic disorder (Klein 1964). Other TCAs, notably clomipramine, have also been found to have significant anxiolytic properties (den Boer et al. 1990 Modigh 1992). Studies of ethnic differences in the pharmacokinetics of the TCAs in... 

Clinicians should be aware of a few drug interactions with Zolpidem. Flumazenil acts as an antagonist to the hypnotic effects of zolpidem. There is decreased alertness when zolpidem is combined with cimetidine. There is an increase in anterograde amnesia in volunteers treated with a combination of imipramine and zolpidem. Haloperidol, ranitidine, chlorpromazine, warfarin, and digoxin, along with cimetidine and flumazenil, do not alter the pharmacokinetics of zolpidem (Salva and Costa, 1995). 

Kurtz DL, Bergstrom RF, Goldberg MJ, et al. The effect of sertraline on the pharmacokinetics of desipramine and imipramine. Clin Pharmacol Ther 1997 62 145-156. 

Reisby N, Gram LF, Bech P, Nagy A, Petersen GO, Ortmann J, Ibsen I, Dencker SJ, Jacobsen O, Krautwald O, Sondergaard I, Christiansen J. Imipramine clinical effects and pharmacokinetic variability. Psychopharmacology (Berl) 1977 54(3) 263-72. 

Pharmacokinetic and pharmacodynamic profiles of olanzapine have been extensively reviewed (266). Olanzapine does not inhibit CYP isozymes, and no clinically significant metabolic interactions were found of olanzapine with aminophylline, biperiden, diazepam, ethanol, fluoxetine, imipramine, lithium, or R/S-warfarin. 

When a dmg is in its unionised form it will more readily diffuse from the urine to the blood. In an acidic urine, acidic drugs will diffuse back into the blood from the urine. Acidic compounds such as nitrofurantoin are excreted faster when the urinary pH is alkaline. Amfetamine, imipramine and amitriptyline are excreted more rapidly in acidic urine. The control of urinary pH in studies of pharmacokinetics is thus vital. It is difficult, however, to find compounds to use by the oral route for deliberate adjustment of urinary pH. Sodium bicarbonate and ammonium chloride may be used but are unpalatable. Intravenous administration of acidifying salt solutions presents one approach, especially for the forced diuresis of basic dmgs in cases of poisoning. 

Lin K-M, Poland RE, Nuccio I, et al Ethnicity and imipramine response I. pharmacokinetic and pharmacogenetic influences. Submitted for publication... 

Much of the study of interethnic differences in the pharmacokinetics and pharmacodynamics of psychotropic medications has involved TCAs and differences between Asians and Caucasians (Pi et al. 1993a). As with antipsychotics, there are clinical reports that Asians require lower doses of TCAs (Pi and Gray 1998 Pi et al. 1993a). It has also been suggested that Asians show a therapeutic response at lower blood levels of TCAs (Yamashita and Asano 1979), suggesting pharmacodynamic differences. Other studies of prescribing patterns have failed to confirm this and found that the daily doses of amitriptyline, imipramine, doxepin, and nortriptyline prescribed by psychiatrists at 29 medical schools in 9 Asian countries were the same as those used in the United States (Pi et al. 1985). It was also reported that Asians and whites need similar doses of at least 150 mg/day to attain recommended therapeutic blood concentrations (Kinzie et al. 1987). 

Rutledge, D.R. Abadi, A.H. Lopez, L.M. Beaudreau, C.A. High-performance liquid chromatographic determination of diltiazem and two of its metabolites in plasma using a short alkyl chain silanol deactivated column. J.Chromatogr., 1993, 615, 111-116 [plasma extracted metabolites imipramine IS LOD 4 n mL pharmacokinetics interfering theophylline simultaneous desipramine, propranolol, verapamil non-interfering aspirin, atenolol, caffeine, ibuprofen, lidocaine, metoprolol, nifedipine]... 

Johnson, K.E. Pieper, J.A. An HPLC method for the determination of diltiazem and three of its metabolites in serum. J.Liq.Chromatogr., 1990, 13, 951-960 [extracted metabolites serum doxepin (IS) LOD 3 ng/mL non-interfering carbamazepine, chlorpromazine, gedlopamil, imipramine, lidocaine, prochlorperazine, quinidine, thioridazine, trimeprazine pharmacokinetics]... 

Rasymas, A.K. Boudoulas, H. MacKichan, J. Determination of verapamil enantiomers in serum following racemate administration using HPLC. J.Liq.Chromatogr, 1992, 15, 3013-3029 [chiral achiral fluorescence detection extracted metabolites imipramine (IS) LOD 0.2 ng/mL pharmacokinetics]... 

Antidepressants Fluvoxamlne, a potent inhibitor of the cytochrome P450 enzymes CYP1A2 and CYP2C19 and a moderate inhibitor of CYP3A4, has been reported to cause a 5-10-fold elevation of plasma clozapine concentration. Fluoxetine and paroxetine may also increase plasma clozapine concentrations, while citalopram and sertraline have been reported to cause minimal or no elevation of plasma levels of clozapine. To date, in vivo studies with a combined olanzapine-imipramine regimen have not revealed any pharmacokinetic interactions. 

Table 21.9. Pharmacokinetics of the Tricyclic Nonselective Reuptake Inhibit) Parameters Amitripytline Clomipramine Doxepin Imipramine Trim...

The pharmacokinetics for imipramine are shown in Tabie 21.9. imipramine is compieteiy absorbed from the Gi tract, imipramine is primariiy metaboiized by CYP2D6 to its 2- and 10-hydroxyiated metaboiites and N-demethyiated via CYP2C19 and CYP1A2 to desipramine, its N-monodemethyiated metaboiite, an SNRi. 

No pharmacokinetic interaction was seen in 6 healthy subjects given single doses of chloroquine 300 mg and imipramine 50 mg. See also Drugs that prolong the QT interval + Other drugs that prolong the QT interval , p.257. 

Onyeji CO, Toriola TA, Ogunbona FA. Lack of pharmacokinetic interaction between chlcco-quine and imipramine. TherDrugMonit 993>) 15,43-6. 

No pharmacokinetic interaction occurs between imipramine or mirtazapine and olanzapine, but the additive effects of clomipramine and olanzapine was thought to have caused a seizure in one patient. 

A randomised, crossover study in 9 healthy men given single doses of olanzapine 5 mg and imipramine 75 mg found no clinically relevant pharmacokinetic or pharmacodynamic interactions between the two drugs. This would seem to confirm in vitro studies using human liver mi-crosomes, which demonstrated that olanzapine causes minimal inhibition of the cytochrome P450 isoenzyme CYP2D6, an enzyme involved in the metabolism of the tricyclic antidepressants. However, one case report describes seizures, thought to be caused by the additive effects of olanzapine... 

Po in SG, Thyrum FT, Alva G, Carreon D, Yeh C, Kalali TV Arvanitis LA Effect of fluoxetine and imipramine on the pharmacokinetics and tolerability of die antipsychotic quetiapine. J Clin Psychopharmacol (2002) 22,174-82. 

Methylphenidate can increase the levels and rate of response to tricyclic antidepressants. This has led to both increased beneficial and adverse effects. No significant pharmacokinetic interaction has been reported between desipramine and dexamfetamine or methylphenidate. An isolated report describes a blood dyscrasia in a child given methylphenidate and imipramine. 

Two groups of 6 healthy subjects were given a single 100-mg dose of either imipramine or desipramine alone, and then again on day 10 of a 14-day course of ketoconazole 200 mg once daily. It was found that the ketoconazole caused the oral clearance of the imipramine to fall by 17%, its half-life to rise by 15% and the AUC of desipramine, derived from the imipramine, to fall by 9%. No significant changes in the pharmacokinetics of the desipramine were seen. ... 

Spina E, Avenoso A, Campo GM, Scordo MG, Caputi AP, Pemcca E. Effect of ketoconazole on the pharmacokinetics of imipramine and desipramine in healthy subjects. BrJ Clin Pharmacol (1997) 43,315-8. 

Zaleplon. A single 75-mg dose of imipramine had no efifeet on the pharmacokinetics of zaleplon 20 mg, and psychomotor tests showed only short term additive effects lasting 1 to 2 hours. ... 

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