Hydrocortisone Phenobarbital

Human colon microsomal cytochrome P450 enzymes can demethylate 1,2-dimethylhydrazine, yielding formaldehyde, and activities in the descending colon are always higher than in the ascending or transverse colon (Newaz et al., 1983). A-Demethylation was also detected in microsomes from a human colon tumour line, adenocarcinoma LS 174T cells. The activity was inducible by phenobarbital and/or hydrocortisone. 

Drugs that are known to be substrates of P-gp include antihistamines (e.g. terfenadine), digoxin, ciclosporin, hydrocortisone and other steroids and drugs used in chemotherapy (e.g. paclitaxel, vinblastine). Ciclosporin, in addition to being a substrate of P-gp, is also an inhibitor of P-gp. Drugs known to induce P-gp include morphine, dexamethasone, phenobarbital, rifampin and St John s wort. Inhibitors of P-gp include amiodarone, amitriptyline, atorvastatin, chlorpromazine, ciclosporin, erythromycin, fluphenazine, haloperidol, quinidine, ritonavir and verapamil,... 

Unfortunately, only relatively few of the many papers published on povidone deal with its influence on bioavailability in vivo. However, where results are available, they almost always show an improvement in bioavailability. Figs. 49 to 51 show the effect of coprecipitation with povidone on the bioavailability of different active substances administered by different routes. Fig. 49 shows, as a typical example, the oral bioavailability of a nifedipine coprecipitate in the rat, Fig. 50 shows the rectal bioavailability of a phenobarbital coprecipitate in rabbits, while Fig. 51 shows the effect of a hydrocortisone coprecipitate on the human skin after percutaneous administration. In all three cases, the same dose of the pure active substance without povidone was applied for reference. 

Extracted carbamazepine, ethosuximide, phenobarbital, primidone Simultaneous amobarbital, barbital, chlordiazepoxide, codeine, ethotoin, glutethimide, hexobarbital, hydrocortisone, mephenytoin, mephobarbital, metharbital, methsuximide, nitrazepam, phenacetin, phensixximide, secobarbital Noninterfering acetaminophen, acetazolamide, amphetamine, bilirubin, caffeine, diazepam, dimenhydrinate, meperidine, meprobamate, methamphetamine, methaqualone, methylphenidate, nicotine, propoxyphene, theophylline, valproic acid Interfering pentobarbital... 

Simultaneous acetaminophen, aldosterone, allopurinol, amitriplyline, caffeine, calcitriol, cephalothin, chlordiazepoxide, chlorothiazide, corticosterone, cortisone, dexamethasone, diazepam, ephedrine, ethinyl estradiol, furosemide, hydrocortisone, ibuprofen, imipra-mine, indomethacin, mechlorethamine, methylprednisone, metolazone, nandrolone, naproxen, phenacetin, phenobarbital, phen3doin, probenecid, progesterone, propranolol, sulfasalazine, testosterone, theophylline, vincristine... 

Noninterfering acetaminophen, aspirin, chlorpheniramine, ethenzamide, hydrocortisone, phenacetin, phenobarbital, phenylbutazone, phenytoin, prednisolone, prednisone, salicylic acid, trimethadione, vitamin B1... 

The interaction between the corticosteroids and phenobarbital is well documented, well established and of clinical importance. Concurrent use need not be avoided but the outcome should be monitored. Increase the corticosteroid dosage as necessary. The extent of the increase is variable. Dex-amethasone, hydrocortisone, " methylprednisolone, prednisone and prednisolone are all known to be affected. Prednisone and prednisolone appear to be less affected than methylprednisolone and may be preferred. Be alert for the same interaction with other corticosteroids and other barbiturates, which also are enzyme-inducers, although direct evidence seems to be lacking. The dexamethasone adrenal suppression test may be expected to be unreliable in those taking phenobarbital, just as it is with pheny-toin, another potent enzyme-inducer. See Corticosteroids + Phenytoin , p.1059. 

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