Cimetidine Ethanol

Figure 16 Experimental and Estimated solubility of Cimetidine in Ethanol / Water for the full regression case.

A predicted solubility curve for Cimetidine in Ethanol is shown in Figure 18. The affect of temperature on solubility occurs through two mechanisms the ideal solubility effect (Eq. 3), and the temperature dependence of the activity coefficient, y. The second affect is not correlated by the NRTL-SAC model, however it is generally accepted that in most phase equilibria problems the affect of temperature on the activity coefficient is relatively small compared to the affect on ideal solubility. A further degree of caution should be applied when extrapolating in this manner, until experimental data are collected. 

Figure 18 Predicted solubility curve for Cimetidine in Ethanol, full regression case.

Amiodarone Benzodiazepines Chloramphenicol Cimetidine Disulfiram Ethanol (acute ingestion) Fluconazole Isoniazid Metronidazole Miconazole Omeprazole Phenacemide Phenylbutazone Succinimides Sulfonamides Trimethoprim Valproic acid Salicylates Tricyclic antidepressants Valproic acid... 

Drugs that may affect metronidazole include barbiturates and cimetidine. Drugs that may be affected by metronidazole include anticoagulants, disulfiram, ethanol, hydantoins, and lithium. 

To an ethanolic suspension of cimetidine, concentrated hydrocholoric acid and ethyl acetate are added, the product is collected, washed with ethyl acetate, and dried. The schematic is illustrated belcw ... 

The separation of cimetidine and its metabolites is usually carried out by extraction of the biological medium with 1-octanol fran an aqueous alkaline pH solution followed by mixing, addition of an internal standard and centrifugation. The extraction with octanol is repeated and the combined extracts are re-extracted with dilute hydrochloric acid. The aqueous acid solution is then separated, ethanol is added and mixed. This is then followed by saturating the mixture with a large amount of potassium or sodium carbonate to "salt out" the ethanol layer which contains the cimetidine and its metabolite, the sulfoxide. Several different internal standards have been used Metiamide, 1-methyl-3-[2-[[(5-methyl-imidazole-4-yl) -methyl] thio]ethyl]-2-thiourea,19 31 39 (N-cyano-N1-methy1-N"-(3-(4-imidazolyl)-propyl)guanidine32, and 13-hydroxy-theophylline. 0 After extraction the samples are either evaporated to dryness and reconstituted with a known amount of ethanol, injected directly or dissolved in the mobile phase for the HPLC analysis. 

CabaUeria J, Baraona E, Rodamilans M, Lieber CS. Effects of cimetidine on gastric alcohol dehydrogenase activity and blood ethanol levels.. Gastroenterology 1989 96(2 Pt 1) 388-92. 

Seitz HK, Bosche J, Czygan P, Veith S, Simon B, Kommerell B. Increased blood ethanol levels following cimetidine but not ranitidine. Lancet 1983 1(8327) 760. 

The cytochrome P450 (CYP) system is the group of enzymes of most interest to psychiatrists. These enzymes show considerable genetic variation, and certain isozymes can be induced by specific substrates such as phenobarbital, ethanol, and steroids. They can also be inhibited by various medications that are potent competitive inhibitors of the enzymes (e.g., cimetidine and ketoconazole). 

Clinically important, potentially hazardous interactions with alcohol, cimetidine, CNS depressant, erythromycin, ethanol, ketoconazole, nefazodone, nelfinavir, olanzapine, rifampin, ritonavir, tricyclic antidepressants... 

Drug Interactions. Phenobarbital is a potent enzyme inducer and may increase the elimination of any drug metabolized by CYP450-or UGT-mediated metabolism. Valproic acid, phenytoin, felbamate, cimetidine, and chloramphenicol inhibit phenobarbital metabolism, necessitating a decrease in dose. Ethanol increases the metabolism of phenobarbital. ... 

Ainino-l,2,4-triazole, cimetidine, diethyldithiocarbamate,dihydrocapsaicin, dimethysulfoxide, disulfiram, ethanol, 4-methylpyrazole, phenylisothiocyanate... 

Most abundant isoform wide substrate range inhibited by cimetidine, macrolides, azoles, and ethanol (acute) induced by general P450 inducers such as carbamazepine, phenobarbital, phenytoin, and rifampin and by ethanol (chronic). 

Metoclopramide increases gastric transit time, enhancing the absorption of substances absorbed in the small intestine (e.g., ethanol, cyclosporin) and decreasing the absorption of substances absorbed in the stomach (e.g., cimetidine, digoxin). Anticholinergic drugs and dopamine-function-enhancing substances such as levodopa reduce the effectiveness of metoclopramide. Because metoclopramide releases catecholamine, it should be used cautiously with monoamine oxidase inhibitors such as tranylcypromine. Because metoclopramide inhibits plasma cholinesterase, it increases the effectiveness of succinylcholine, a skeletal muscle relaxant. 

Cinnamomum cassia (Chinese cinnamon), a species containing numerous flavonic derivatives (epicatechol, epicatechol-O-glucoside and dicyclic-O-glucosides), has been used in traditional Chinese medicine for its analgesic, antipyretic and tonic properties [90]. The aqueous extract showed an effect comparable to cimetidine, a potent antisecretory agent, preventing the ulceration induced by stress and cold, and contrarily to cimetidine, it inhibited the ulceration induced by serotonin. It also reduced the secretion of acid and pepsin and increased the mucosal blood flow. Similar gastroprotective results were obtained in other experimental models, such as in the lesions induced by phenylbutazone and oral administration of ethanol. 

Because benzodiazepines do not significantly induce the synthesis of hepatic CYPs, chronic benzodiazepine administration usually does not result in the accelerated metabolism of benzodiazepines or other substances. Cimetidine and oral contraceptives inhibit N-dealkylation and 3-hydroxylation of benzodiazepines, as do ethanol, isoniazid, and phenytoin to a lesser degree. These reactions usually are reduced to a greater extent in elderly patients and in patients with chronic liver disease than are those involving conjugation. 

The urine of some patients may be reddish brown due to pigments derived from the drug. Oxidative metabolism of metronidazole is induced by phenobarbital, prednisone, rifampin, and possibly ethanol and is inhibited by cimetidine. 

Paclitaxel has very limited solubility and must be administered in a vehicle of 50% ethanol and 50% polyethoxylated castor oil (CREMOPHOR EL), a formation likely responsible for a high rate of hypersensitivity reactions. Patients receiving this formulation are protected by pretreatment with a histamine Hj receptor antagonist such as diphenhydramine, an receptor antagonist such as cimetidine fsee Chapter 24), and a glucocorticoid such as dexamethasone (see Chapter 59). Docetaxel, which is somewhat more soluble, is administered in polysorbate 80 and causes a lower incidence of hypersensitivity reactions. Pretreatment with dexamethasone is required to prevent progressive, and often disabling, fluid retention. 

Dobrilla G, de Pretis G, Piazzi L, Chilovi F, Comberlato M, Valentini M, Pastorino A, Val-laperta P. Is ethanol metabolism affected by oral administration of cimetidine and ranitidine at therapeutic doses Hepatogastroenterology (1984) 31,35-7. 

Jonsson K-A, Jones AW, Boslrom H, Andersson T. Lack of effect of cmeprazole, cimetidine, and ranitidine on the phaim acokinetics of ethanol in fastii male vohmleers. EurJ CUn Phar macol (1992) 42, 209-12. 

Brown ASJM, James OFW. Omeprazole, ranitidine and cimetidine have no effect on peak blood ethanol concentrations, first pass metabolism or area under the time-ethanol curve under real-life drinking cor i or)s.AUmentPhcuinacolTher 99Z) 12,141-5. 

Battiston L, Tulissi P, Moretti M, Pozzato G. Lansoprazole and ethanol metabolism comparison with omeprazole and cimetidine. Pharmacol Toxicol (1997) 81, 247-52. 

Ochs HR, Greenblatt DJ, Verbuig-Ochs B, Harmatz JS, Grehl H Dispositionof clotiazepam influence of age, sex, oral contraceptives, cimetidine, isc iiazid and ethanol. EurJ Clin Pharmacol 9ZA) 26, 55-9... 

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